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2 juni 2017: Bronnen: Phytomedicine, en Journal of Traditional and Complementary Medicine
Ik denk dat wel algemeen bekend is dat soja en genisteine vormen van hormoon gerelateerde kanker, waaronder borstkanker, prostaatkanker, eierstokkanker en endometriose kan remmen en voorkomen.Zie anders onze studielijsten: https://kanker-actueel.nl/NL/literatuurlijsten-niet-toxische-middelen-en-behandelingen-per-kankersoort-en-aanvullend-op-chemo-operatie-en-bestraling.html
Hier twee studies die bewijzen dat genisteine de klachten van endometriose kan verminderen en kan voorkomen dat endometriose uitgroeit tot kanker. En ook een reviewstudie van studies die aantonen dat genisteine eierstokkanker kan voorkomen en wellicht kan afremmen en recidief langer kan uitstellen.
In deze kleinschalige studie: Genistein aglycone: A new therapeutic approach to reduce endometrial hyperplasia verminderde na 6 maanden bij 42% van de patienten die genistein aglyconegebruikten de symptomen / klachten (histologische bevestiging van 29%) vergeleken met 47% bij patiënten die norethisterone acetate gebruikten (histologischge bevestiging van 31%), maar slechts bij 12% in de placebogroep waarbij bij 19% uit die groep de kalchten verergerden met 19 procent en de endometriose alleen maar erger werd. Zie verder abstract hieronder.
In deze reviewstudie: Genistein as a Potential Anticancer Agent against Ovarian Cancer wordt een overzicht gegeven van een groot aantal studies en daaruit blijkt dat genisteine effect heeft op bepaalde mutaties en eiwitexpressies en 'pathways' behorend bij vormen van hormoongerelateerde vormen van kanker waaronder met name eierstokkanker. Hier de conclusie uit de reviewstudie die ik niet verder vertaal maar anders vertaalt u dit met hulp van google vertaaltool rechtsboven dit artikel.
Conclusie:
Collectively, previous epidemiological and experimental studies have suggested that genistein may play promising roles as a chemopreventive or therapeutic agent against ovarian cancer. In addition to its hormonal action, the anticancer effects of genistein are related to multiple cellular signaling pathways such as PTK, Akt, NF-κB, MMP, and Bax/Bcl-2. Because the successful treatment of ovarian cancer is limited mainly by the development of chemotherapy resistance, genistein is expected to play a role in sensitizing multiresistant ovarian cancer cells and have additive effects with conventional chemotherapeutic agents. Although some clinical trials are now being performed to identify the role of genistein as an anticancer agent against various types of cancers, there is currently no registered clinical trial on ovarian cancer. Further research should be performed to identify the role of genistein in ovarian carcinogenesis.
Hier enkele grafieken uit deze studie van opgenomen studies in deze reviewstudie (klik op de blauwe links in de kolom refences om een bepaalde studie in te zien. Onderaan het abstract en referentielijst oinderaan dit artikel.
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Reference Study design Study period Participants Race/Country Measure of soy intake Adjusted OR (95% CI) Zhang et al., 2004 CCS 1999–2000 254 EOC cases and 652 age-matched controls Chinese/China Soy foods (g/day): ≥ 136.4 vs. ≤ 47.0
Isoflavones (mg/day): ≥ 32.8 vs. ≤ 11.6
Genistein (mg/day): ≥ 20.9 vs. ≤ 6.60.50 (0.31–0.82)
0.51 (0.31–0.85)
0.50 (0.30–0.84)Sakauchi et al., 2007 PCS 1988–2003(15) 77 EOC cases among 63,541 women Japanese/Japan Soybean curd (times/week)
Almost every day vs. ≤ 1–20.61
(0.26–1.45)Rossi et al., 2008 CCS 1992–1997 1031 EOC cases and 2411 controls Italian/Italy Isoflavone (μg/day)
≥ 32.5 vs. ≤ 12.80.51
(0.37–0.69)Chang et al., 2007 PCS 1995–2003(8) 280 EOC cases among 97,275 women Mainly white (84%), Hispanic (4%), Asian (3%), black (2%), Native American (2%)/U.S. Isoflavone (mg/day) ≥ 3 vs. ≤ 1
Genistein (mg/day) ≥ 1.1 vs. ≤ 0.30.56 (0.33–0.96)
0.65 (0.42–1.02)Bandera et al., 2011 CCS 2004–2008 205 EOC cases and 390 controls White (87%), black (4%), Hispanic (4%)/U.S. Total phytoestrogen (mg/1000 kcal)
≥ 1395 vs. ≤ 5340.62
(0.38–1.00)Hedelin et al., 2011 PCS 1991–2007(16) 163 EOC cases (117 invasive cancer, 6 BT) among 47,140 women Swedish/Sweden Isoflavone (μg/day)
≥ 16 vs. ≤ 0.741.26
(0.79–2.01) -
CCS: case-control study, PCS: prospective cohort study, EOC: epithelial ovarian cancer, BT: borderline tumor
In vitro Studies
Results from previous epidemiological studies have raised the interest regarding the role of genistein as a chemopreventive agent, and therefore, researchers have attempted to determine the molecular mechanisms of this compound. Numerous studies have shown that genistein has inhibitory effects on ovarian cancer cells and tumor growth in vitro. Table 2 shows the anticancer effects of genistein on ovarian cancer cells from recently published in vitro studies.
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Reference Materials Cell type Description Measure of interest Results Choi et al., 2007 Genistein SK-OV-3 Human ovarian cancer cell Cell proliferation (MTT assay)
Cell cycle distribution (FACS)
Cytotoxicity (LDH)
Apoptosis (caspase-3 activity)Inhibition of cell proliferation in a dose- and time-dependent manner
Arrest at G2/M phase
Increased LDH release
Increased caspase-3 activityAhmed et al., 2011 ITB-301, genistein derivative SK-OV-3, ES2, HeyA8, HeyA8-MDR Human ovarian cancer cell Cell proliferation (crystal violet staining)
Cell cycle distribution (FACS)
Apoptosis (caspase-3/7 activity)
Microtubule depolymerization (tubulin polymerization assay kit)Induced microtubule depolymerization in a dose- and time-dependent manner
No change in efflux-mediated drug resistance
Cytotoxic effect of ITB-301 on a multidrug-resistant cell lineSolomon et al., 2008 Genistein A2780, C200 Human ovarian cancer cell Cell survival and apoptosis
(MTT assay, histone-DNA ELISA)
Indirect measure of apoptosis:
Bcl-2, Bcl-xL, c-IAP1, survivin
(Western blot analysis)
NF-κB (EMSA)Downregulation of antiapoptotic genes
Decreased NF-κB
Genistein pretreatment with chemotherapy was effective in both PS and PR ovarian cancer cell linesGercel-Taylor et al., 2004 Genistein 5 ovarian cancer cell lines from stage IIIc Human ovarian cancer cell Cell growth (sulforhodamine B and colony formation assays)
Apoptosis (caspase-3 activity)Induced caspase-3 activity
Additive effect of cell proliferation inhibition with cisplatin, topotecan, and paclitaxelLuo et al., 2008 Genistein OVCAR-3 Human ovarian cancer cell Cytotoxicity (CytoTox 96)
Proliferation (CellTiter 96)
VEGF (RT-PCR, ELISA)Induced cell growth
Inhibited VEGF expressionRucinska et al., 2007 G8CG CHO Chinese hamster ovary cell Cytotoxicity (MTT assay)
DNA damage (Comet assay)
Apoptosis
(Hoechst 33258/propidium iodide staining technique)
ROS (fluorescence probe)Cytotoxic at high concentrations
Antioxidant properties at lower concentrationsChen et al., 2001 Genistein Caov-3, NIH: OVCAR-3 Human ovarian cancer cell Cell proliferation (MTT assay))
ER, GAPDH (RT-PCR))
IL-6 (ELISA))
TGF-b (immunoassay)Inhibited cell proliferation
Inhibited IL-6 synthesis
Increased TGF-b productionGossner et al., 2007 Genistein A2780, CaOV3, ES2 Human ovarian cancer cell Analysis of apoptosis (FACS)
Autophagy (microtubule-associated LC3)
Akt (western blot analysis), glucose uptakeInduced apoptosis
Inhibited glucose uptake, reduced phosphorylated Akt
Induced autophagic cell death -
MTT: methyl thiazolyl tetrazolium, FACS: fluorescence-activated cell sorting, LDH: lactate dehydrogenase, ELISA: enzyme-linked immunosorbent assay, EMSA: electrophoretic mobility shift assay, PS: platinum sensitive, PR: platinum resistant, VEGF: vascular endothelial growth factor, RT-PCR: reverse transcription polymerase chain reaction, G8CG: genistein 8-C-glucoside, ROS: reactive oxygen species, ER: estrogen receptor, GADPH: glyceraldehyde-3-phosphate dehydrogenase, LC3: light chain 3
Hier de respectievelijke abstracten en referentielijst:
genistein aglycone might be useful for the management of endometrial hyperplasia without atypia in women that cannot be treated with progestin.
Phytomedicine
Genistein aglycone: A new therapeutic approach to reduce endometrial hyperplasia
- a
- Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Messina, Italy
- b
- Department of Obstetrical and Gynaecological Sciences, University of Messina, Building A, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Italy
- c
- Department of Human Pathology, University of Messina, Building D, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Messina, Italy
- d
- Department of Biochemical, Physiological and Nutritional Sciences, Section of Physiology and Human Nutrition, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria, Gazzi, 98125, Messina, Italy
Collectively, previous epidemiological and experimental studies have suggested that genistein may play promising roles as a chemopreventive or therapeutic agent against ovarian cancer. In addition to its hormonal action, the anticancer effects of genistein are related to multiple cellular signaling pathways such as PTK, Akt, NF-κB, MMP, and Bax/Bcl-2.
Volume 2, Issue 2, April–June 2012, Pages 96–104
Genistein as a Potential Anticancer Agent against Ovarian Cancer
- Open Access funded by Center for Food and Biomolecules, National Taiwan University
- Under a Creative Commons license
Abstract
Genistein is known as the major component of isoflavone, which is present in high-soy diets. Genistein has received much attention because of its chemopreventive and therapeutic effects on various types of cancers. Numerous studies have shown that genistein has antineoplastic effects against ovarian cancer. Several epidemiological studies have shown that women who have high consumption of isoflavones have a relatively low incidence of ovarian cancer. Genistein inhibits ovarian carcinogenesis by pleiotropic mechanisms. A higher affinity to estrogen receptor β is one probable explanation for its ability to reduce the risk of ovarian cancer. Genistein also targets multiple cellular signal transduction pathways associated with cell cycle regulation and apoptosis. In addition, genistein has been suggested to have antiangiogenic and antioxidant activities. Herein, we summarize recent results from epidemiological and experimental studies to identify the role of genistein in ovarian cancer. Further studies are needed to achieve conclusive results and determine the clinical applications of genistein.
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