Zie ook de literatuurlijsten niet-toxische behandelingen en middelen van arts-bioloog drs. Engelbert Valstar waarin vitamine C veel voorkomt in verschillende lijsten.
Zie ook in gerelateerde artikelen
22 april 2020: Bron: Biomolecules. 2020 Jan; 10(1): 79
Dat vitamine C een rol kan spelen bij kanker, al of niet in combinatie met andere behandelingen is inmiddels wel bekend. Zie anders in gerelateerde artikelen.
Vitamine C blijkt ook een 'genezende' rol te spelen bij de zogeheten kankerstamcellen die verantwoordelijk zijn voor uitzaaiingen en recidieven. Hier een artikel dat dit proces beschrijft met veel gedetailleerde uitleg. Ik heb het abstract zo goed als mogelijk vertaald.
Kanker blijft een van de meest gevreesde en gevreesde ziekten in dit tijdperk van de moderne geneeskunde, eist het leven van velen op en beïnvloedt de levenskwaliteit van verschillende anderen over de hele wereld, ondanks grote vooruitgang in de diagnose, behandeling, palliatieve zorg en de immense middelen geïnvesteerd in kankeronderzoek.
Terwijl onderzoek bij kanker zich grotendeels heeft gericht op het neoplasma / de tumor en de kankercellen waaruit de tumor bestaat, meer recentelijk is onderzoek gedaan naar het bestaan, de proliferatie, differentiatie, migratie en invasie van kankerstamcellen (CSC's) en de rol die kankerstamcellen (CSC's) spelen bij tumorvorming, ziekteprogressie, uitzaaiingen, medicijnresistentie en terugval / recidief van de ziekte en hebben wijdverspreide belangstelling gekregen in het kankeronderzoek.
Hoewel de conventionele therapeutische benaderingen zoals chirurgie, chemotherapie en bestraling effectieve kankerbehandelingen zijn, richten deze behandelingsmodaliteiten zich vaak niet op de kankerstamcellen (CSC's), die later de bron worden van het terugkeren van de ziekte. Een meerderheid van de antikankermiddelen is gericht op snel delende kankercellen en normale cellen en heeft daarom bijwerkingen die niet worden verwacht.
Het richten op kankerstamcellen (CSC's) blijft een uitdaging vanwege hun afwijkende karakter met een lage proliferatiesnelheid en een verhoogd mechanisme voor resistentie tegen geneesmiddelen.
Ascorbinezuur / Vitamine C (Vit.C), een krachtige antioxidant, is een cofactor voor verschillende biosynthetische en genregulerende enzymen en levert een vitale bijdrage aan de immuunafweer van het lichaam, en bleek deficiënt te zijn bij patiënten met vergevorderde stadia van kanker. Vitamine C heeft aan belang gewonnen bij de behandeling van kanker vanwege het vermogen om de redoxstatus van de cel te moduleren en epigenetische modificaties en significante rollen in HIF1α-signalering te beïnvloeden.
Studies hebben aangetoond dat intraveneuze toediening van Vit.C in farmacologische doses selectief tumorcellen doodt en kankerstamcellen (CSC's) zoekt bij toediening samen met chemotherapeutische geneesmiddelen. In het huidige artikel geven we een diepgaande evaluatie van hoe Vitamine C een belangrijke rol speelt bij het richten op kankerstamcellen (CSC's) en het mogelijke gebruik ervan als aanvullend, preventief aan een behandeling of als combinatiebehandeling met chemo, radiotherapie of hormoontherapie bij de behandeling van kanker in z'n algemeenheid.
Alle conventionele kankertherapieën zoals hormonale therapie, chirurgie, immunotherapie en anti-angiogenesetherapie slagen om twee redenen niet in het langetermijneffect. [1] Al deze behandelingen zijn niet gericht op de kankerstamcellen (CSC's) mede vanwege het onvoorspelbare onbedoelde toxische effect op de normale cellen. [2]
Recente studies hebben aangetoond dat intraveneuze toediening van vitamine C (Vit.C), samen met de conventionele kankertherapie, succesvol is in het verminderen van kankerprogressie en daarmee hoopvol is voor veel kankerpatiënten over de hele wereld. [9]
Zie onderstaande grafiek hoe kankerstamcellen een rol spelen bij tumorvorming en uitzaaiingen:
Current and future involvement of cancer stem cells (CSCs) on cancer treatment: Current situation describes the effect of cancer therapy on unpredicted non-targeted effects on normal cells and metastasis/recurrence of cancer after several years due to the presence of CSCs along with tumor cells. Current research reveals that standard cancer therapy with CSC targets provides much more efficient outcomes on the tumor progression with elimination of CSCs. In the future, further studies could be focused on miRNA (microRNA), cancer organoid, resistance mechanism by CSCs and could enter the clinical phases, promising a better outcome for the cancer patients.
Het volledige studierapport: Combination Therapy with Vitamin C Could Eradicate Cancer Stem Cells geeft een gedetailleerde omschrijving hoe en wat extra vitamine C kan betekenen in een behandeling van kankerstamcellen en hoe daarmee een recidief te voorkomen is.
Hier het abstract van het arftikel en de referentielijst behorend bij dit artikel:
Combination Therapy with Vitamin C Could Eradicate Cancer Stem Cells
This article has been
cited by other articles in PMC.
References
1.
Ghosh D., Venkataramani P., Nandi S., Bhattacharjee S. CRISPR-Cas9 a boon or bane: The bumpy road ahead to cancer therapeutics. Cancer Cell Int. 2019;19:12. doi: 10.1186/s12935-019-0726-0. [PMC free article] [PubMed] [CrossRef] [Google Scholar]3.
Reya T., Morrison S.J., Clarke M.F., Weissman I.L. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–111. doi: 10.1038/35102167. [PubMed] [CrossRef] [Google Scholar]4.
Dean M., Fojo T., Bates S. Tumour stem cells and drug resistance. Nat. Rev. Cancer. 2005;5:275–284. doi: 10.1038/nrc1590. [PubMed] [CrossRef] [Google Scholar]5.
Ahmad G., Amiji M.M. Cancer stem cell-targeted therapeutics and delivery strategies. Expert Opin. Drug Deliv. 2017;14:997–1008. doi: 10.1080/17425247.2017.1263615. [PubMed] [CrossRef] [Google Scholar]7.
Peiris-Pages M., Martinez-Outschoorn U.E., Pestell R.G., Sotgia F., Lisanti M.P. Cancer stem cell metabolism. Breast Cancer Res. 2016;18:55. doi: 10.1186/s13058-016-0712-6. [PMC free article] [PubMed] [CrossRef] [Google Scholar]8.
Jones R.J., Matsui W.H., Smith B.D. Cancer stem cells: Are we missing the target? J. Natl. Cancer Inst. 2004;96:583–585. doi: 10.1093/jnci/djh095. [PubMed] [CrossRef] [Google Scholar]9.
Carr A.C., Cook J. Intravenous Vitamin C for Cancer Therapy—Identifying the Current Gaps in Our Knowledge. Front. Physiol. 2018;9:1182. doi: 10.3389/fphys.2018.01182. [PMC free article] [PubMed] [CrossRef] [Google Scholar]10.
Liskova A., Kubatka P., Samec M., Zubor P., Mlyncek M., Bielik T., Samuel S.M., Zulli A., Kwon T.K., Busselberg D. Dietary Phytochemicals Targeting Cancer Stem Cells. Molecules. 2019;24:899. doi: 10.3390/molecules24050899. [PMC free article] [PubMed] [CrossRef] [Google Scholar]11.
Rafalski V.A., Mancini E., Brunet A. Energy metabolism and energy-sensing pathways in mammalian embryonic and adult stem cell fate. J. Cell Sci. 2012;125:5597–5608. doi: 10.1242/jcs.114827. [PMC free article] [PubMed] [CrossRef] [Google Scholar]12.
Muz B., de la Puente P., Azab F., Azab A.K. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia. 2015;3:83–92. doi: 10.2147/HP.S93413. [PMC free article] [PubMed] [CrossRef] [Google Scholar]13.
Khan A.Q., Ahmed E.I., Elareer N.R., Junejo K., Steinhoff M., Uddin S. Role of miRNA-Regulated Cancer Stem Cells in the Pathogenesis of Human Malignancies. Cells. 2019;8:840. doi: 10.3390/cells8080840. [PMC free article] [PubMed] [CrossRef] [Google Scholar]15.
Nechuta S., Lu W., Chen Z., Zheng Y., Gu K., Cai H., Zheng W., Shu X.O. Vitamin supplement use during breast cancer treatment and survival: A prospective cohort study. Cancer Epidemiol. Biomark. Prev. 2011;20:262–271. doi: 10.1158/1055-9965.EPI-10-1072. [PMC free article] [PubMed] [CrossRef] [Google Scholar]16.
Hao J., Zhao S., Zhang Y., Zhao Z., Ye R., Wen J., Li J. Emerging role of microRNAs in cancer and cancer stem cells. J. Cell. Biochem. 2014;115:605–610. doi: 10.1002/jcb.24702. [PubMed] [CrossRef] [Google Scholar]17.
Croker A.K., Goodale D., Chu J., Postenka C., Hedley B.D., Hess D.A., Allan A.L. High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J. Cell. Mol. Med. 2009;13:2236–2252. doi: 10.1111/j.1582-4934.2008.00455.x. [PMC free article] [PubMed] [CrossRef] [Google Scholar]19.
Hwang-Verslues W.W., Chang P.H., Wei P.C., Yang C.Y., Huang C.K., Kuo W.H., Shew J.Y., Chang K.J., Lee E.Y., Lee W.H. miR-495 is upregulated by E12/E47 in breast cancer stem cells, and promotes oncogenesis and hypoxia resistance via downregulation of E-cadherin and REDD1. Oncogene. 2011;30:2463–2474. doi: 10.1038/onc.2010.618. [PubMed] [CrossRef] [Google Scholar]20.
Fiorillo M., Toth F., Sotgia F., Lisanti M.P. Doxycycline, Azithromycin and Vitamin C (DAV): A potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs) Aging. 2019;11:2202–2216. doi: 10.18632/aging.101905. [PMC free article] [PubMed] [CrossRef] [Google Scholar]21.
Al-Hajj M., Wicha M.S., Benito-Hernandez A., Morrison S.J., Clarke M.F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA. 2003;100:3983–3988. doi: 10.1073/pnas.0530291100. [PMC free article] [PubMed] [CrossRef] [Google Scholar]22.
Asadzadeh Z., Mansoori B., Mohammadi A., Aghajani M., Haji-Asgarzadeh K., Safarzadeh E., Mokhtarzadeh A., Duijf P.H.G., Baradaran B. microRNAs in cancer stem cells: Biology, pathways, and therapeutic opportunities. J. Cell. Physiol. 2019;234:10002–10017. doi: 10.1002/jcp.27885. [PubMed] [CrossRef] [Google Scholar]23.
Okuda H., Xing F., Pandey P.R., Sharma S., Watabe M., Pai S.K., Mo Y.Y., Iiizumi-Gairani M., Hirota S., Liu Y., et al. miR-7 suppresses brain metastasis of breast cancer stem-like cells by modulating KLF4. Cancer Res. 2013;73:1434–1444. doi: 10.1158/0008-5472.CAN-12-2037. [PMC free article] [PubMed] [CrossRef] [Google Scholar]24.
Ma W., Xiao G.G., Mao J., Lu Y., Song B., Wang L., Fan S., Fan P., Hou Z., Li J., et al. Dysregulation of the miR-34a-SIRT1 axis inhibits breast cancer stemness. Oncotarget. 2015;6:10432–10444. doi: 10.18632/oncotarget.3394. [PMC free article] [PubMed] [CrossRef] [Google Scholar]25.
Wang Y., Yu Y., Tsuyada A., Ren X., Wu X., Stubblefield K., Rankin-Gee E.K., Wang S.E. Transforming growth factor-beta regulates the sphere-initiating stem cell-like feature in breast cancer through miRNA-181 and ATM. Oncogene. 2011;30:1470–1480. doi: 10.1038/onc.2010.531. [PMC free article] [PubMed] [CrossRef] [Google Scholar]26.
ClinicalTrials.gov Ph 2 Trial of Vitamin C & G-FLIP (Low Doses Gemcitabine, 5FU, Leucovorin, Irinotecan, Oxaliplatin) for Pancreatic Cancer) [(accessed on 2 October 2019)]; Available online: https://clinicaltrials.gov/ct2/show/NCT01905150?term=vitamin+c&recrs=ade&cond=Pancreatic+Cancer&cntry=US&rank=1.27.
Lechner A., Leech C.A., Abraham E.J., Nolan A.L., Habener J.F. Nestin-positive progenitor cells derived from adult human pancreatic islets of Langerhans contain side population (SP) cells defined by expression of the ABCG2 (BCRP1) ATP-binding cassette transporter. Biochem. Biophys. Res. Commun. 2002;293:670–674. doi: 10.1016/S0006-291X(02)00275-9. [PubMed] [CrossRef] [Google Scholar]28.
Hasegawa S., Eguchi H., Nagano H., Konno M., Tomimaru Y., Wada H., Hama N., Kawamoto K., Kobayashi S., Nishida N., et al. MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer. Br. J. Cancer. 2014;111:1572–1580. doi: 10.1038/bjc.2014.454. [PMC free article] [PubMed] [CrossRef] [Google Scholar]29.
ClinicalTrials.gov Trial of Ascorbic Acid (AA) + Nanoparticle Paclitaxel Protein Bound + Cisplatin + Gemcitabine (AA NABPLAGEM) (AA NABPLAGEM) [(accessed on 2 October 2019)]; Available online: https://clinicaltrials.gov/ct2/show/NCT03410030?term=vitamin+c&recrs=ade&cond=Pancreatic+Cancer&cntry=US&phase=123&rank=2.30.
Tomuleasa C., Mosteanu O., Susman S., Cristea V. ALDH as a tumor marker for pancreatic cancer. J. Gastrointest. Liver Dis. 2011;20:443–444. author reply 444. [PubMed] [Google Scholar]31.
Bao B., Ali S., Ahmad A., Azmi A.S., Li Y., Banerjee S., Kong D., Sethi S., Aboukameel A., Padhye S.B., et al. Hypoxia-induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment. PLoS ONE. 2012;7:e50165. doi: 10.1371/journal.pone.0050165. [PMC free article] [PubMed] [CrossRef] [Google Scholar]32.
ClinicalTrials.gov High Dose Vitamin C Intravenous Infusion in Patients with Resectable or Metastatic Solid Tumor Malignancies. [(accessed on 2 October 2019)]; Available online: https://clinicaltrials.gov/ct2/show/NCT03146962?term=vitamin+c&recrs=ade&cond=Pancreatic+Cancer&cntry=US&phase=123&rank=3.33.
Li C., Heidt D.G., Dalerba P., Burant C.F., Zhang L., Adsay V., Wicha M., Clarke M.F., Simeone D.M. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–1037. doi: 10.1158/0008-5472.CAN-06-2030. [PubMed] [CrossRef] [Google Scholar]34.
Sureban S.M., May R., Qu D., Weygant N., Chandrakesan P., Ali N., Lightfoot S.A., Pantazis P., Rao C.V., Postier R.G., et al. DCLK1 regulates pluripotency and angiogenic factors via microRNA-dependent mechanisms in pancreatic cancer. PLoS ONE. 2013;8:e73940. doi: 10.1371/journal.pone.0073940. [PMC free article] [PubMed] [CrossRef] [Google Scholar]35.
Immervoll H., Hoem D., Sakariassen P.O., Steffensen O.J., Molven A. Expression of the “stem cell marker” CD133 in pancreas and pancreatic ductal adenocarcinomas. BMC Cancer. 2008;8:48. doi: 10.1186/1471-2407-8-48. [PMC free article] [PubMed] [CrossRef] [Google Scholar]36.
Lu Y., Lu J., Li X., Zhu H., Fan X., Zhu S., Wang Y., Guo Q., Wang L., Huang Y., et al. MiR-200a inhibits epithelial-mesenchymal transition of pancreatic cancer stem cell. BMC Cancer. 2014;14:85. doi: 10.1186/1471-2407-14-85. [PMC free article] [PubMed] [CrossRef] [Google Scholar]37.
Pramanik D., Campbell N.R., Karikari C., Chivukula R., Kent O.A., Mendell J.T., Maitra A. Restitution of tumor suppressor microRNAs using a systemic nanovector inhibits pancreatic cancer growth in mice. Mol. Cancer Ther. 2011;10:1470–1480. doi: 10.1158/1535-7163.MCT-11-0152. [PMC free article] [PubMed] [CrossRef] [Google Scholar]38.
Corney D.C., Flesken-Nikitin A., Godwin A.K., Wang W., Nikitin A.Y. MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 2007;67:8433–8438. doi: 10.1158/0008-5472.CAN-07-1585. [PubMed] [CrossRef] [Google Scholar]39.
ClinicalTrials.gov Treatment of Newly Diagnosed Ovarian Cancer with Antioxidants. [(accessed on 2 October 2019)]; Available online: https://clinicaltrials.gov/ct2/show/NCT00228319?term=vitamin+c&recrs=ade&cond=Ovarian+cancer&cntry=US&phase=123&rank=1.40.
Dou J., Jiang C., Wang J., Zhang X., Zhao F., Hu W., He X., Li X., Zou D., Gu N. Using ABCG2-molecule-expressing side population cells to identify cancer stem-like cells in a human ovarian cell line. Cell Biol. Int. 2011;35:227–234. doi: 10.1042/CBI20100347. [PubMed] [CrossRef] [Google Scholar]41.
Stewart J.M., Shaw P.A., Gedye C., Bernardini M.Q., Neel B.G., Ailles L.E. Phenotypic heterogeneity and instability of human ovarian tumor-initiating cells. Proc. Natl. Acad. Sci. USA. 2011;108:6468–6473. doi: 10.1073/pnas.1005529108. [PMC free article] [PubMed] [CrossRef] [Google Scholar]42.
ClinicalTrials.gov A Phase 2 Trial of High-Dose Ascorbate in Glioblastoma Multiforme. [(accessed on 2 October 2019)]; Available online: https://clinicaltrials.gov/ct2/show/NCT02344355?term=vitamin+c&recrs=ade&cond=Glioblastoma&cntry=US&phase=123&rank=1.43.
Cui S.Y., Wang R., Chen L.B. MicroRNA-145: A potent tumour suppressor that regulates multiple cellular pathways. J. Cell. Mol. Med. 2014;18:1913–1926. doi: 10.1111/jcmm.12358. [PMC free article] [PubMed] [CrossRef] [Google Scholar]44.
Shang C., Guo Y., Hong Y., Liu Y.H., Xue Y.X. MiR-21 up-regulation mediates glioblastoma cancer stem cells apoptosis and proliferation by targeting FASLG. Mol. Biol. Rep. 2015;42:721–727. doi: 10.1007/s11033-014-3820-3. [PubMed] [CrossRef] [Google Scholar]45.
Turchi L., Debruyne D.N., Almairac F., Virolle V., Fareh M., Neirijnck Y., Burel-Vandenbos F., Paquis P., Junier M.P., Van Obberghen-Schilling E., et al. Tumorigenic potential of miR-18A* in glioma initiating cells requires NOTCH-1 signaling. Stem Cells. 2013;31:1252–1265. doi: 10.1002/stem.1373. [PubMed] [CrossRef] [Google Scholar]46.
Ying Z., Li Y., Wu J., Zhu X., Yang Y., Tian H., Li W., Hu B., Cheng S.Y., Li M. Loss of miR-204 expression enhances glioma migration and stem cell-like phenotype. Cancer Res. 2013;73:990–999. doi: 10.1158/0008-5472.CAN-12-2895. [PMC free article] [PubMed] [CrossRef] [Google Scholar]47.
Godlewski J., Nowicki M.O., Bronisz A., Williams S., Otsuki A., Nuovo G., Raychaudhury A., Newton H.B., Chiocca E.A., Lawler S. Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. Cancer Res. 2008;68:9125–9130. doi: 10.1158/0008-5472.CAN-08-2629. [PubMed] [CrossRef] [Google Scholar]48.
Geng J., Luo H., Pu Y., Zhou Z., Wu X., Xu W., Yang Z. Methylation mediated silencing of miR-23b expression and its role in glioma stem cells. Neurosci. Lett. 2012;528:185–189. doi: 10.1016/j.neulet.2012.08.055. [PubMed] [CrossRef] [Google Scholar]49.
Summer R., Kotton D.N., Sun X., Ma B., Fitzsimmons K., Fine A. Side population cells and Bcrp1 expression in lung. Am. J. Physiol Lung Cell. Mol. Physiol. 2003;285:97–104. doi: 10.1152/ajplung.00009.2003. [PubMed] [CrossRef] [Google Scholar]50.
Hu J., Qiu M., Jiang F., Zhang S., Yang X., Wang J., Xu L., Yin R. MiR-145 regulates cancer stem-like properties and epithelial-to-mesenchymal transition in lung adenocarcinoma-initiating cells. Tumour Biol. 2014;35:8953–8961. doi: 10.1007/s13277-014-2158-8. [PubMed] [CrossRef] [Google Scholar]51.
ClinicalTrials.gov Pharmacological Ascorbate for Lung Cancer. [(accessed on 2 October 2019)]; Available online: https://clinicaltrials.gov/ct2/show/NCT02420314?term=vitamin+c&recrs=ade&cond=lung+cancer&cntry=US&phase=123&rank=1.52.
Jiang F., Qiu Q., Khanna A., Todd N.W., Deepak J., Xing L., Wang H., Liu Z., Su Y., Stass S.A., et al. Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol. Cancer Res. 2009;7:330–338. doi: 10.1158/1541-7786.MCR-08-0393. [PMC free article] [PubMed] [CrossRef] [Google Scholar]53.
Xu W., Ji J., Xu Y., Liu Y., Shi L., Liu Y., Lu X., Zhao Y., Luo F., Wang B., et al. MicroRNA-191, by promoting the EMT and increasing CSC-like properties, is involved in neoplastic and metastatic properties of transformed human bronchial epithelial cells. Mol. Carcinog. 2015;54:148–161. doi: 10.1002/mc.22221. [PubMed] [CrossRef] [Google Scholar]54.
ClinicalTrials.gov A Phase 2 Study Adding Ascorbate to Chemotherapy and Radiation Therapy for NSCLC (XACT-LUNG) [(accessed on 2 October 2019)]; Available online: https://clinicaltrials.gov/ct2/show/NCT02905591?term=vitamin+c&recrs=ade&cond=lung+cancer&cntry=US&phase=123&rank=2.55.
Xi S., Xu H., Shan J., Tao Y., Hong J.A., Inchauste S., Zhang M., Kunst T.F., Mercedes L., Schrump D.S. Cigarette smoke mediates epigenetic repression of miR-487b during pulmonary carcinogenesis. J. Clin. Investig. 2013;123:1241–1261. doi: 10.1172/JCI61271. [PMC free article] [PubMed] [CrossRef] [Google Scholar]56.
Bertolini G., Roz L., Perego P., Tortoreto M., Fontanella E., Gatti L., Pratesi G., Fabbri A., Andriani F., Tinelli S., et al. Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment. Proc. Natl. Acad. Sci. USA. 2009;106:16281–16286. doi: 10.1073/pnas.0905653106. [PMC free article] [PubMed] [CrossRef] [Google Scholar]57.
King C.E., Cuatrecasas M., Castells A., Sepulveda A.R., Lee J.S., Rustgi A.K. LIN28B promotes colon cancer progression and metastasis. Cancer Res. 2011;71:4260–4268. doi: 10.1158/0008-5472.CAN-10-4637. [PMC free article] [PubMed] [CrossRef] [Google Scholar]58.
Huang E.H., Hynes M.J., Zhang T., Ginestier C., Dontu G., Appelman H., Fields J.Z., Wicha M.S., Boman B.M. Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res. 2009;69:3382–3389. doi: 10.1158/0008-5472.CAN-08-4418. [PMC free article] [PubMed] [CrossRef] [Google Scholar]59.
Dalerba P., Dylla S.J., Park I.K., Liu R., Wang X., Cho R.W., Hoey T., Gurney A., Huang E.H., Simeone D.M., et al. Phenotypic characterization of human colorectal cancer stem cells. Proc. Natl. Acad. Sci. USA. 2007;104:10158–10163. doi: 10.1073/pnas.0703478104. [PMC free article] [PubMed] [CrossRef] [Google Scholar]60.
Jaksch M., Munera J., Bajpai R., Terskikh A., Oshima R.G. Cell cycle-dependent variation of a CD133 epitope in human embryonic stem cell, colon cancer, and melanoma cell lines. Cancer Res. 2008;68:7882–7886. doi: 10.1158/0008-5472.CAN-08-0723. [PMC free article] [PubMed] [CrossRef] [Google Scholar]61.
ClinicalTrials.gov TET2 Mutations in Myelodysplastic Syndromes and Acute Myeloid Leukemia with Azacitidine + Ascorbic Acid. [(accessed on 2 October 2019)]; Available online: https://clinicaltrials.gov/ct2/show/NCT03397173?term=vitamin+c&recrs=ade&cond=Leukemia&cntry=US&phase=123&rank=1.62.
Scheibner K.A., Teaboldt B., Hauer M.C., Chen X., Cherukuri S., Guo Y., Kelley S.M., Liu Z., Baer M.R., Heimfeld S., et al. MiR-27a functions as a tumor suppressor in acute leukemia by regulating 14-3-3theta. PLoS ONE. 2012;7:e50895. doi: 10.1371/journal.pone.0050895. [PMC free article] [PubMed] [CrossRef] [Google Scholar]63.
ClinicalTrials.gov Therapeutic Use of Intravenous Vitamin C in Allogeneic Stem Cell Transplant Recipients. [(accessed on 2 October 2019)]; Available online: https://clinicaltrials.gov/ct2/show/NCT03613727?term=vitamin+c&recrs=ade&cond=Leukemia&cntry=US&phase=123&rank=2.64.
ClinicalTrials.gov Ascorbic Acid and Combination Chemotherapy in Treating Patients with Relapsed or Refractory Lymphoma. [(accessed on 2 October 2019)]; Available online: https://clinicaltrials.gov/ct2/show/NCT03418038?term=vitamin+c&recrs=ade&cond=Lymphoma&cntry=US&phase=123&rank=1.65.
Ma S., Tang K.H., Chan Y.P., Lee T.K., Kwan P.S., Castilho A., Ng I., Man K., Wong N., To K.F., et al. miR-130b Promotes CD133+ liver tumor-initiating cell growth and self-renewal via tumor protein 53-induced nuclear protein 1. Cell Stem Cell. 2010;7:694–707. doi: 10.1016/j.stem.2010.11.010. [PubMed] [CrossRef] [Google Scholar]66.
Han Y.C., Park C.Y., Bhagat G., Zhang J., Wang Y., Fan J.B., Liu M., Zou Y., Weissman I.L., Gu H. microRNA-29a induces aberrant self-renewal capacity in hematopoietic progenitors, biased myeloid development, and acute myeloid leukemia. J. Exp. Med. 2010;207:475–489. doi: 10.1084/jem.20090831. [PMC free article] [PubMed] [CrossRef] [Google Scholar]67.
Babashah S., Sadeghizadeh M., Hajifathali A., Tavirani M.R., Zomorod M.S., Ghadiani M., Soleimani M. Targeting of the signal transducer Smo links microRNA-326 to the oncogenic Hedgehog pathway in CD34+ CML stem/progenitor cells. Int. J. Cancer. 2013;133:579–589. doi: 10.1002/ijc.28043. [PubMed] [CrossRef] [Google Scholar]68.
Morris V.A., Zhang A., Yang T., Stirewalt D.L., Ramamurthy R., Meshinchi S., Oehler V.G. MicroRNA-150 expression induces myeloid differentiation of human acute leukemia cells and normal hematopoietic progenitors. PLoS ONE. 2013;8:e75815. doi: 10.1371/journal.pone.0075815. [PMC free article] [PubMed] [CrossRef] [Google Scholar]69.
ClinicalTrials.gov Docetaxel with or without Ascorbic Acid in Treating Patients with Metastatic Prostate Cancer. [(accessed on 2 October 2019)]; Available online: https://clinicaltrials.gov/ct2/show/NCT02516670?term=vitamin+c&recrs=ade&cond=Prostate+cancer&cntry=US&phase=123&rank=1.70.
Hellsten R., Johansson M., Dahlman A., Sterner O., Bjartell A. Galiellalactone inhibits stem cell-like ALDH-positive prostate cancer cells. PLoS ONE. 2011;6:e22118. doi: 10.1371/journal.pone.0022118. [PMC free article] [PubMed] [CrossRef] [Google Scholar]71.
Chang Y.L., Zhou P.J., Wei L., Li W., Ji Z., Fang Y.X., Gao W.Q. MicroRNA-7 inhibits the stemness of prostate cancer stem-like cells and tumorigenesis by repressing KLF4/PI3K/Akt/p21 pathway. Oncotarget. 2015;6:24017–24031. doi: 10.18632/oncotarget.4447. [PMC free article] [PubMed] [CrossRef] [Google Scholar]72.
Collins A.T., Berry P.A., Hyde C., Stower M.J., Maitland N.J. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65:10946–10951. doi: 10.1158/0008-5472.CAN-05-2018. [PubMed] [CrossRef] [Google Scholar]73.
Liu C., Kelnar K., Liu B., Chen X., Calhoun-Davis T., Li H., Patrawala L., Yan H., Jeter C., Honorio S., et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat. Med. 2011;17:211–215. doi: 10.1038/nm.2284. [PMC free article] [PubMed] [CrossRef] [Google Scholar]74.
Vander Griend D.J., Karthaus W.L., Dalrymple S., Meeker A., DeMarzo A.M., Isaacs J.T. The role of CD133 in normal human prostate stem cells and malignant cancer-initiating cells. Cancer Res. 2008;68:9703–9711. doi: 10.1158/0008-5472.CAN-08-3084. [PMC free article] [PubMed] [CrossRef] [Google Scholar]75.
Hatanaka K., Okada M. Retarded nuclear migration in Drosophila embryos with aberrant F-actin reorganization caused by maternal mutations and by cytochalasin treatment. Development. 1991;111:909–920. [PubMed] [Google Scholar]78.
King C.G., Waugh W.A. The Chemical Nature of Vitamin C. Science. 1932;75:357–358. doi: 10.1126/science.75.1944.357-a. [PubMed] [CrossRef] [Google Scholar]79.
Parrow N.L., Leshin J.A., Levine M. Parenteral ascorbate as a cancer therapeutic: A reassessment based on pharmacokinetics. Antioxid. Redox Signal. 2013;19:2141–2156. doi: 10.1089/ars.2013.5372. [PMC free article] [PubMed] [CrossRef] [Google Scholar]80.
Burzle M., Hediger M.A. Functional and physiological role of vitamin C transporters. Curr. Top. Membr. 2012;70:357–375. doi: 10.1016/B978-0-12-394316-3.00011-9. [PubMed] [CrossRef] [Google Scholar]81.
Englard S., Seifter S. The biochemical functions of ascorbic acid. Annu. Rev. Nutr. 1986;6:365–406. doi: 10.1146/annurev.nu.06.070186.002053. [PubMed] [CrossRef] [Google Scholar]82.
Tsukaguchi H., Tokui T., Mackenzie B., Berger U.V., Chen X.Z., Wang Y., Brubaker R.F., Hediger M.A. A family of mammalian Na+-dependent L-ascorbic acid transporters. Nature. 1999;399:70–75. doi: 10.1038/19986. [PubMed] [CrossRef] [Google Scholar]83.
Wang H., Dutta B., Huang W., Devoe L.D., Leibach F.H., Ganapathy V., Prasad P.D. Human Na+-dependent vitamin C transporter 1 (hSVCT1): Primary structure, functional characteristics and evidence for a non-functional splice variant. Biochim. Biophys. Acta Biomembr. 1999;1461:1–9. doi: 10.1016/S0005-2736(99)00182-0. [PubMed] [CrossRef] [Google Scholar]84.
Daruwala R., Song J., Koh W.S., Rumsey S.C., Levine M. Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2. FEBS Lett. 1999;460:480–484. doi: 10.1016/S0014-5793(99)01393-9. [PubMed] [CrossRef] [Google Scholar]85.
Wang Y., Mackenzie B., Tsukaguchi H., Weremowicz S., Morton C.C., Hediger M.A. Human vitamin C (L-ascorbic acid) transporter SVCT1. Biochem. Biophys. Res. Commun. 2000;267:488–494. doi: 10.1006/bbrc.1999.1929. [PubMed] [CrossRef] [Google Scholar]86.
Corpe C.P., Eck P., Wang J., Al-Hasani H., Levine M. Intestinal dehydroascorbic acid (DHA) transport mediated by the facilitative sugar transporters, GLUT2 and GLUT8. J. Biol. Chem. 2013;288:9092–9101. doi: 10.1074/jbc.M112.436790. [PMC free article] [PubMed] [CrossRef] [Google Scholar]87.
Rumsey S.C., Kwon O., Xu G.W., Burant C.F., Simpson I., Levine M. Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. J. Biol. Chem. 1997;272:18982–18989. doi: 10.1074/jbc.272.30.18982. [PubMed] [CrossRef] [Google Scholar]88.
Rumsey S.C., Daruwala R., Al-Hasani H., Zarnowski M.J., Simpson I.A., Levine M. Dehydroascorbic acid transport by GLUT4 in Xenopus oocytes and isolated rat adipocytes. J. Biol. Chem. 2000;275:28246–28253. doi: 10.1074/jbc.M000988200. [PubMed] [CrossRef] [Google Scholar]89.
Vera J.C., Rivas C.I., Fischbarg J., Golde D.W. Mammalian facilitative hexose transporters mediate the transport of dehydroascorbic acid. Nature. 1993;364:79–82. doi: 10.1038/364079a0. [PubMed] [CrossRef] [Google Scholar]90.
Tu H., Li H., Wang Y., Niyyati M., Wang Y., Leshin J., Levine M. Low Red Blood Cell Vitamin C Concentrations Induce Red Blood Cell Fragility: A Link to Diabetes Via Glucose, Glucose Transporters, and Dehydroascorbic Acid. EBioMedicine. 2015;2:1735–1750. doi: 10.1016/j.ebiom.2015.09.049. [PMC free article] [PubMed] [CrossRef] [Google Scholar]91.
Gillberg L., Orskov A.D., Liu M., Harslof L.B.S., Jones P.A., Gronbaek K. Vitamin C—A new player in regulation of the cancer epigenome. Semin. Cancer Biol. 2018;51:59–67. doi: 10.1016/j.semcancer.2017.11.001. [PubMed] [CrossRef] [Google Scholar]92.
Mayland C.R., Bennett M.I., Allan K. Vitamin C deficiency in cancer patients. Palliat. Med. 2005;19:17–20. doi: 10.1191/0269216305pm970oa. [PubMed] [CrossRef] [Google Scholar]93.
Klimant E., Wright H., Rubin D., Seely D., Markman M. Intravenous vitamin C in the supportive care of cancer patients: A review and rational approach. Curr. Oncol. 2018;25:139–148. doi: 10.3747/co.25.3790. [PMC free article] [PubMed] [CrossRef] [Google Scholar]94.
Kagohara L.T., Stein-O’Brien G.L., Kelley D., Flam E., Wick H.C., Danilova L.V., Easwaran H., Favorov A.V., Qian J., Gaykalova D.A., et al. Epigenetic regulation of gene expression in cancer: Techniques, resources and analysis. Brief. Funct. Genom. 2018;17:49–63. doi: 10.1093/bfgp/elx018. [PMC free article] [PubMed] [CrossRef] [Google Scholar]95.
Padayatty S.J., Katz A., Wang Y., Eck P., Kwon O., Lee J.H., Chen S., Corpe C., Dutta A., Dutta S.K., et al. Vitamin C as an antioxidant: Evaluation of its role in disease prevention. J. Am. Coll. Nutr. 2003;22:18–35. doi: 10.1080/07315724.2003.10719272. [PubMed] [CrossRef] [Google Scholar]96.
Wilson M.K., Baguley B.C., Wall C., Jameson M.B., Findlay M.P. Review of high-dose intravenous vitamin C as an anticancer agent. Asia Pac. J. Clin. Oncol. 2014;10:22–37. doi: 10.1111/ajco.12173. [PubMed] [CrossRef] [Google Scholar]98.
Lv H., Wang C., Fang T., Li T., Lv G., Han Q., Yang W., Wang H. Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2. NPJ Precis. Oncol. 2018;2:1. doi: 10.1038/s41698-017-0044-8. [PMC free article] [PubMed] [CrossRef] [Google Scholar]99.
Ngo B., Van Riper J.M., Cantley L.C., Yun J. Targeting cancer vulnerabilities with high-dose vitamin C. Nat. Rev. Cancer. 2019;19:271–282. doi: 10.1038/s41568-019-0135-7. [PMC free article] [PubMed] [CrossRef] [Google Scholar]102.
Klein E.A., Thompson I.M., Jr., Tangen C.M., Crowley J.J., Lucia M.S., Goodman P.J., Minasian L.M., Ford L.G., Parnes H.L., Gaziano J.M., et al. Vitamin E and the risk of prostate cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) JAMA. 2011;306:1549–1556. doi: 10.1001/jama.2011.1437. [PMC free article] [PubMed] [CrossRef] [Google Scholar]103.
Omenn G.S., Goodman G.E., Thornquist M.D., Balmes J., Cullen M.R., Glass A., Keogh J.P., Meyskens F.L., Valanis B., Williams J.H., et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N. Engl. J. Med. 1996;334:1150–1155. doi: 10.1056/NEJM199605023341802. [PubMed] [CrossRef] [Google Scholar]104.
Rahal A., Kumar A., Singh V., Yadav B., Tiwari R., Chakraborty S., Dhama K. Oxidative stress, prooxidants, and antioxidants: The interplay. BioMed Res. Int. 2014;2014:761264. doi: 10.1155/2014/761264. [PMC free article] [PubMed] [CrossRef] [Google Scholar]105.
Wondrak G.T. Redox-directed cancer therapeutics: Molecular mechanisms and opportunities. Antioxid. Redox Signal. 2009;11:3013–3069. doi: 10.1089/ars.2009.2541. [PMC free article] [PubMed] [CrossRef] [Google Scholar]108.
Rychtarcikova Z., Lettlova S., Tomkova V., Korenkova V., Langerova L., Simonova E., Zjablovskaja P., Alberich-Jorda M., Neuzil J., Truksa J. Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism. Oncotarget. 2017;8:6376–6398. doi: 10.18632/oncotarget.14093. [PMC free article] [PubMed] [CrossRef] [Google Scholar]109.
Kiessling M.K., Klemke C.D., Kaminski M.M., Galani I.E., Krammer P.H., Gulow K. Inhibition of constitutively activated nuclear factor-kappaB induces reactive oxygen species- and iron-dependent cell death in cutaneous T-cell lymphoma. Cancer Res. 2009;69:2365–2374. doi: 10.1158/0008-5472.CAN-08-3221. [PubMed] [CrossRef] [Google Scholar]110.
Liberti M.V., Locasale J.W. Correction to: ‘The Warburg Effect: How Does it Benefit Cancer Cells?’: [Trends in Biochemical Sciences, 41 (2016) 211] Trends Biochem. Sci. 2016;41:287. doi: 10.1016/j.tibs.2016.01.004. [PubMed] [CrossRef] [Google Scholar]111.
Yun J., Rago C., Cheong I., Pagliarini R., Angenendt P., Rajagopalan H., Schmidt K., Willson J.K., Markowitz S., Zhou S., et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science. 2009;325:1555–1559. doi: 10.1126/science.1174229. [PMC free article] [PubMed] [CrossRef] [Google Scholar]112.
Bhattacharjee S., Nandi S. Rare Genetic Diseases with Defects in DNA Repair: Opportunities and Challenges in Orphan Drug Development for Targeted Cancer Therapy. Cancers. 2018;10:298. doi: 10.3390/cancers10090298. [PMC free article] [PubMed] [CrossRef] [Google Scholar]113.
Bhattacharjee S., Nandi S. Synthetic lethality in DNA repair network: A novel avenue in targeted cancer therapy and combination therapeutics. IUBMB Life. 2017;69:929–937. doi: 10.1002/iub.1696. [PubMed] [CrossRef] [Google Scholar]115.
Melamed P., Yosefzon Y., David C., Tsukerman A., Pnueli L. Tet Enzymes, Variants, and Differential Effects on Function. Front. Cell Dev. Biol. 2018;6:22. doi: 10.3389/fcell.2018.00022. [PMC free article] [PubMed] [CrossRef] [Google Scholar]116.
Mastrangelo D., Pelosi E., Castelli G., Lo-Coco F., Testa U. Mechanisms of anti-cancer effects of ascorbate: Cytotoxic activity and epigenetic modulation. Blood Cells Mol. Dis. 2018;69:57–64. doi: 10.1016/j.bcmd.2017.09.005. [PubMed] [CrossRef] [Google Scholar]117.
Bonuccelli G., De Francesco E.M., de Boer R., Tanowitz H.B., Lisanti M.P. NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Identification of Vitamin C and CAPE as natural products targeting “stemness” Oncotarget. 2017;8:20667–20678. doi: 10.18632/oncotarget.15400. [PMC free article] [PubMed] [CrossRef] [Google Scholar]118.
Kulis M., Esteller M. DNA methylation and cancer. Adv. Genet. 2010;70:27–56. doi: 10.1016/B978-0-12-380866-0.60002-2. [PubMed] [CrossRef] [Google Scholar]119.
Hore T.A., von Meyenn F., Ravichandran M., Bachman M., Ficz G., Oxley D., Santos F., Balasubramanian S., Jurkowski T.P., Reik W. Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naive pluripotency by complementary mechanisms. Proc. Natl. Acad. Sci. USA. 2016;113:12202–12207. doi: 10.1073/pnas.1608679113. [PMC free article] [PubMed] [CrossRef] [Google Scholar]120.
De Francesco E.M., Bonuccelli G., Maggiolini M., Sotgia F., Lisanti M.P. Vitamin C and Doxycycline: A synthetic lethal combination therapy targeting metabolic flexibility in cancer stem cells (CSCs) Oncotarget. 2017;8:67269–67286. doi: 10.18632/oncotarget.18428. [PMC free article] [PubMed] [CrossRef] [Google Scholar]121.
De Francesco E.M., Ozsvari B., Sotgia F., Lisanti M.P. Dodecyl-TPP Targets Mitochondria and Potently Eradicates Cancer Stem Cells (CSCs): Synergy With FDA-Approved Drugs and Natural Compounds (Vitamin C and Berberine) Front. Oncol. 2019;9:615. doi: 10.3389/fonc.2019.00615. [PMC free article] [PubMed] [CrossRef] [Google Scholar]123.
Cimmino L., Abdel-Wahab O., Levine R.L., Aifantis I. TET family proteins and their role in stem cell differentiation and transformation. Cell Stem Cell. 2011;9:193–204. doi: 10.1016/j.stem.2011.08.007. [PMC free article] [PubMed] [CrossRef] [Google Scholar]125.
Ko M., An J., Pastor W.A., Koralov S.B., Rajewsky K., Rao A. TET proteins and 5-methylcytosine oxidation in hematological cancers. Immunol. Rev. 2015;263:6–21. doi: 10.1111/imr.12239. [PMC free article] [PubMed] [CrossRef] [Google Scholar]126.
Guillamot M., Cimmino L., Aifantis I. The Impact of DNA Methylation in Hematopoietic Malignancies. Trends Cancer. 2016;2:70–83. doi: 10.1016/j.trecan.2015.12.006. [PMC free article] [PubMed] [CrossRef] [Google Scholar]127.
Chung T.L., Brena R.M., Kolle G., Grimmond S.M., Berman B.P., Laird P.W., Pera M.F., Wolvetang E.J. Vitamin C promotes widespread yet specific DNA demethylation of the epigenome in human embryonic stem cells. Stem Cells. 2010;28:1848–1855. doi: 10.1002/stem.493. [PubMed] [CrossRef] [Google Scholar]128.
Tahiliani M., Koh K.P., Shen Y., Pastor W.A., Bandukwala H., Brudno Y., Agarwal S., Iyer L.M., Liu D.R., Aravind L., et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324:930–935. doi: 10.1126/science.1170116. [PMC free article] [PubMed] [CrossRef] [Google Scholar]129.
Yin R., Mao S.Q., Zhao B., Chong Z., Yang Y., Zhao C., Zhang D., Huang H., Gao J., Li Z., et al. Ascorbic acid enhances Tet-mediated 5-methylcytosine oxidation and promotes DNA demethylation in mammals. J. Am. Chem. Soc. 2013;135:10396–10403. doi: 10.1021/ja4028346. [PubMed] [CrossRef] [Google Scholar]130.
Ito S., Shen L., Dai Q., Wu S.C., Collins L.B., Swenberg J.A., He C., Zhang Y. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333:1300–1303. doi: 10.1126/science.1210597. [PMC free article] [PubMed] [CrossRef] [Google Scholar]131.
Gustafson C.B., Yang C., Dickson K.M., Shao H., Van Booven D., Harbour J.W., Liu Z.J., Wang G. Epigenetic reprogramming of melanoma cells by vitamin C treatment. Clin. Epigenet. 2015;7:51. doi: 10.1186/s13148-015-0087-z. [PMC free article] [PubMed] [CrossRef] [Google Scholar]132.
Mustafi S., Sant D.W., Liu Z.J., Wang G. Ascorbate induces apoptosis in melanoma cells by suppressing Clusterin expression. Sci. Rep. 2017;7:3671. doi: 10.1038/s41598-017-03893-5. [PMC free article] [PubMed] [CrossRef] [Google Scholar]133.
Knowles H.J., Raval R.R., Harris A.L., Ratcliffe P.J. Effect of ascorbate on the activity of hypoxia-inducible factor in cancer cells. Cancer Res. 2003;63:1764–1768. [PubMed] [Google Scholar]134.
Semenza G.L. Hypoxia-inducible factors: Mediators of cancer progression and targets for cancer therapy. Trends Pharmacol. Sci. 2012;33:207–214. doi: 10.1016/j.tips.2012.01.005. [PMC free article] [PubMed] [CrossRef] [Google Scholar]135.
Kuiper C., Vissers M.C. Ascorbate as a co-factor for Fe- and 2-Oxoglutarate dependent dioxygenases: Physiological activity in tumor growth and progression. Front. Oncol. 2014;4:359. doi: 10.3389/fonc.2014.00359. [PMC free article] [PubMed] [CrossRef] [Google Scholar]137.
Wang F., Li Y.C., Liu L.P., Zhang H.M., Tong S. Circulating Tumor Cells and Tumor Stem Cells Detection in the Peripheral Blood Mononuclear Cells of Breast Cancer. J. Clin. Lab. Anal. 2016;30:616–622. doi: 10.1002/jcla.21911. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Articles from Biomolecules are provided here courtesy of Multidisciplinary Digital Publishing Institute (MDPI)
kankerstamcellen, hoge dosis vitamine C, uitzaaiingen voorkomen, Otto Warburg, overall overleving
Gerelateerde artikelen
Plaats een reactie ...
Reageer op "Combinatietherapie van reguliere behandelingen met vitamine C blijkt kankerstamcellen te vernietigen doordat het energiemetabolisme in kankerstamcellen wordt verstoord."