4 januari 2018: lees ook dit artikel: 

https://kanker-actueel.nl/curcumine-kan-geen-geneesmiddel-zijn-schrijft-henk-timmerman-emeritus-hoogleraar-farmachemie-in-medisch-contact-nav-reviewstudie-the-essential-medicinal-chemistry-of-curcumin.html

4 oktober 2001: In het medische tijdschrift Life Extension is het volgende artikel verschenen over het effect van kurkuma bij kanker. Zie hier de deeplink naar het originele artikel.

LE Magazine September 2001
The Spice of Life Unlocking the power of curcumin 


Imagine if the key to disease prevention was as close as your kitchen shelf. It's not the product of someone's imagination, but the product of years of medical research. Scientists are beginning to take notice of a well-known spice as a potent new preventive therapy against disease, especially cancer. 

by John C. Martin 
edited version

Cancer takes the lives of more than 1,500 people a day-over 5 million since 1990-and is the second leading cause of death in the United States.(1) 
While those statistics are staggering, the medical community is maintaining its 
focus on mechanisms behind the disease and discovering new, potentially effective 
methods of treating it. A similar emphasis is placed on prevention, as more and more 
scientists attempt to uncover the mystery behind 'carcinogenesis,' particularly at 
the genetic level. 

What is drawing the attention of medical oncologists and researchers these days is a substance known as curcumin, a naturally occurring yellow pigment found in the spice tumeric, which is part of the ginger plant family. Tumeric is widely consumed in its countries of origin not only as a spice, but as a medicine for the treatment of a variety of illnesses. It was long ago used as an anti-inflammatory among Indian practitioners.(2) 

Today, curcumin is showing a much broader potential. Not only does the extract work as an antioxidant and anti-inflammatory, but a series of studies in the past four years, focusing on cancer at the cellular level, reveals some exciting findings. For one thing, research is discovering that curcumin is a powerful carcinogenic inhibitor, slowing cancerous cell proliferation by inducing apoptosis, a pre-programmed set of processes within a cell that results in its death. 

Curcumin targets cancer proliferation 

In two recent studies, scientists at New York's Columbia University researched curcumin's therapeutic potential against prostate cancer. In one case last year, the scientists discovered that curcumin had a powerful ability to induce apoptosis and inhibit prostate cell proliferation in vitro by interfering with the cells' protein 
signaling pathways that typically begin the growth process.(3) Just recently, the researchers extended those findings to determine if they could achieve similar results in an animal model.(4) In their latest study, the researchers found that prostate cancer cells that had been injected subcutaneously into mice, which had been fed a diet of 2% curcumin for six weeks, were unable to develop extensively and 
underwent significant apoptosis. "Curcumin could be a potentially therapeutic anti-cancer agent, as it significantly inhibits prostate cancer growth. and has the potential to prevent the progression of this cancer to its hormone refractory state," the study authors concluded. 

Yet prostate cancer is not curcumin's only target. Other cancer investigations have drawn similarly powerful conclusions about this intriguing substance. 

A study this past spring at Wayne State University investigated the effect of curcumin on certain gastrointestinal and colon cancers in the lab.(5) Several immunoblot analyses demonstrated that curcumin blocked cell proliferation and induced apoptosis in both gastrointestinal and colon cancer cell lines. 

A Chinese study published five years earlier found apoptosis is the result when curcumin is introduced to certain skin, colon, kidney and liver cancer cells, either in cultures or in mouse embryo fibroblasts-large, flat oval cells found in connective tissue and inherent in the formation of fibers.(6) 

Other studies using rodents found curcumin is effective in reducing skin inflammation, inhibiting formation of edemas-an abnormal accumulation of cellular fluid, resulting in swelling-and inhibiting skin tumors when the substance is applied topically(7) or orally in concentrations of either 0.2% or 1%.(8) 

Curcumin has had similar effects on other types of cancer. When Polish researchers last year assessed the potency of the extract on lymphoid cells-those found in tissues comprising the lymph nodes- apoptosis resulted, although apoptotic symptoms were uniquely different in the various cells tested, the scientists reported.(9) 

To determine just how effective curcumin might be as an anticarcinogenic agent, it was compared to other compounds and plant extracts in fighting human oral squamous carcinoma.(10) Cell lines were grown in vitro for 72 hours, then the number of cells were counted to determine proliferation and growth. The researchers found that 
curcumin was "considerably more potent" compared to plant phenolics genistein and quercetin in inhibiting this type of cancer. Only cisplatin, a platinum-based substance also tested in the study, was found to be more effective. 

Still more research focused on the effect of curcumin on the development of pulmonary fibrosis by testing a group of rodents.(11) Scientists in India induced the lung disorder in rats, while giving them dosages of curcumin both 10 days prior and then daily throughout the experiment. Remarkably, curcumin demonstrated its powerful anti-inflammatory and anti-fibrotic effect in each rat studied. 

Even breast cancer apparently cannot avoid the power of this extract, which inhibits the growth of breast tumors that result from exposure to environmental estrogens like chemicals and pesticides, when used in combination with isoflavonoids. 
Scientists found the curcumin combination inhibited the growth of estrogen receptor-positive cancer cells in a test tube up to 95%.(12) 

The how's and why's 

What exactly is the mechanism behind curcumin's ability to counteract such a wide array of cancer progression? For several years, medical research focusing on cancer causation has centered on the notion of angiogenesis, the natural blood vessel growth that accompanies metastases. The new blood vessels literally provide nutrition and sustenance to new and growing tumors throughout the body. That may be 
one basis, medical researchers contend, for curcumin's efficacy. In 1998, Harvard researchers tested the substance for its ability to inhibit the growth of endothelial cells; those which line the interior of blood vessels, as well as the growth of new blood vessels in the corneas of mice. 

"Curcumin effectively inhibited endothelial cell proliferation in a dose-dependent manner," they wrote. "Curcumin and its derivatives demonstrated significant inhibition of corneal neovascularization in the mouse.These results indicate that 
curcumin had direct antiangiogenic activity in vitro and in vivo. The activity of curcumin in inhibiting carcinogenesis in diverse organs such as the skin and colon may be mediated in part through angiogenesis inhibition."(13) 

Other studies, such as one by Taiwanese scientists four years ago, examined the molecular mechanisms behind curcumin. They concluded, after studying curcumin's effect on mouse fibroblast cells, that it directly suppresses the expression of nuclear oncogenes, the genetic mutation that launches the process of cancer cell growth, among other things.(14) Other studies have examined the possibility that the 
mechanisms behind curcumin may lie in its ability to block the activity of specific oxidants, and halt signal transduction pathways between cells during the initial 
tumor growth process.(15) 

Curcumin and Cancer

Cancer cells are everything we would like healthy cells to be. They quickly adapt to toxic environments, they readily alter themselves to assure their continued survival, and they are immortal. All of these factors make cancer an extremely difficult disease to treat. 

Chemotherapy drugs have a high rate of failure. That's because these drugs usually kill only specific types of cancer cells within a tumor, or the cancer cells mutate and become resistant to the chemotherapy. 

An example of how cancer cells mutate to ensure their survival can be seen in the recently approved "miracle" drug Gleevec (STI-571). This drug produced striking benefits in the treatment of chronic myeloid leukemia and was quickly approved by the FDA. In a recent clinical trial, however, many patients relapsed as their cancer cells grew resistant. Doctors found that a protein in the cellular DNA targeted by 
STI-571 altered its shape, thus rendering the drug useless in killing these mutant cancer cells. The company that makes STI-571 is already developing strategies to overcome this resistance, but this case of a new drug quickly losing its effectiveness is an illustration of how easily cancer cells will mutate to avoid total eradication. 

Oncologists are increasingly using combination chemotherapy regimens that consist of several cytotoxic drugs that work by different mechanisms of action. The objective is to obliterate as many different types of cancer cells within the tumor, or interfere with as many cancer cell survival factors as possible. Despite the use of 
these potent multi-drug cocktails, 552,000 Americans died of cancer last year. 

Curcumin's potential anti-cancer benefits 

Curcumin may be effective in helping to suppress the escape mechanisms cancer cells use to avoid eradication by conventional therapies. Curcumin has been shown to inhibit cancer cell propagation via the following mechanisms: 

- Inhibiting the epidermal growth factor receptor site (EGFR), in a dose dependent response. Two thirds of all cancers over-express this receptor as a primary means for hyper-proliferation. 

- Inhibiting induction of the basic fibroblast growth factor (bFGF). This is responsible for angiogenesis of endothelial cells. Curcumin's effect here again was a dose dependent response. 

- Inhibiting expression of cyclooxygenase-2 (COX-2), the enzyme involved in the production of PGE2, a tumor promoting prostaglandin. 

- Inhibiting a transcription factor in cancer cells known as nuclear factor kappa beta (NF-kB). Many cancers over-express NF-KB and use this as a growth vehicle to escape cell regulatory control. 

- Increasing expression of nuclear p53 protein in human basal cell carcinomas, human hepatomas and leukemia cell lines. This increases apoptosis (cell death) in these cancers. 

- Inhibiting induction of hepatocyte growth factor (HGF). Over-expression is involved in hepatcellular carcinoma. 

Based on the multiple favorable mechanisms listed above, higher-dose curcumin would appear to be a useful supplement for cancer patients to take. 

As far as curcumin being taken at the same time as chemotherapy drugs, there are contradictions in the scientific literature. Some studies indicate significant benefit, whereas other studies hint at reduced benefit or even potential toxicity. 

Chemotherapy drugs are highly toxic in and of themselves. Whether high-dose curcumin is beneficial or detrimental depends on the type and dose of the chemotherapeutic drug used, the kind of cancer cell being attacked, and the dose of the curcumin. 
Until more definitive information is published, we prefer to err on the side of caution and recommend that chemotherapy patients wait four weeks after their last dose of chemo before taking high-doses of curcumin. 

Life Extension believes the multiple mechanisms of curcumin's actions against cancer cells warrants aggressive further investigation. We will keep members fully informed of our findings, but at this time, we have to take a cautious stance and officially state that high-dose curcumin should not be taken with anti-cancer drugs. 

Cancer patients are faced with many difficult treatment choices. With the exponential increase of new scientific information, conflicts will inevitably occur. Life Extension remains at the forefront in evaluating new scientific data to help members make informed choices. 

Curcumin dosing 

As far as prevention is concerned, the evidence is substantial that curcumin may be effective in protecting against cancer and a host of other diseases. 

For disease prevention purposes, healthy people typically take 900 to 1800 mg of curcumin (with piperine added to enhance assimilation into the bloodstream) a day. Cancer patients often take two to three times this much curcumin-piperine for a six to twelve month period and then taper off the dose. 

Arbiser JL, et al. Curcumin is an in vivo inhibitor of angiogenesis. Mol Med 1998 
Jun;4(6):376-83. 

Gorre, M.E. et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL 
gene mutation or amplification. Science Jun 21, 2001. 

Hanahan D, et al. Less is more, regularly: metronomic dosing of cytotoxic drugs can 
target tumor angiogenesis in mice. J Clin Invest 2000 Apr;105(8):1045-7. 

Jee SH, et al. Curcumin induces a p53-dependent apoptosis 
in human basal cell carcinoma cells. J Invest Dermatol 1998 Oct;111(4):656-61.

Korutla L, et al. Inhibition of ligand-induced activation 
of epidermal growth factor receptor tyrosine phosphorylation by curcumin. Carcinogenesis 1995 Aug;16(8):1741-5.

Seol DW, et al. Transcritional activation of the 
hepatocyte growth factor receptor (c-met) gene by its ligand (hepatocyte growth factor) is mediated through AP-1. Oncogene 2000 Feb 24;19(9):1132-7.

Shoba G,,et al. Influence of piperine on the pharmacokinetics of cuccumin in animals and human volunteers. Planta Med 1998 May;64(4):353-6.

Zhang F, et al. Curcumin inhibits cyclooxygenase-2 
transcription in bile acid phorbol ester-treated human gastrointestinal epithelial cells. Carcinogenesis 1999 Mar;20(3):445-51. 



Article References

1. American Cancer Society. Cancer Statistics. 2000 
figures.

2. American Cancer Society. Complementary and Alternative 
Methods. http://www.cancer.org/alt_therapy/popherbs

3. Dorai T, Gehani N, Katz A. Therapeutic potential of 
curcumin in human prostate cancer. II. Curcumin inhibits tyrosine kinase activity of epidermal growth factor receptor and depletes the protein. Mol Urol 2000 Spring;4(1):1-6.

4. Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits 
proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate 2001 Jun 1;47(4): 293-303.

5. Moragoda L, Jaszewski R, Majumdar AP. Curcumin induced modulation of cell cycle and apoptosis in gastric and colon cancer cells. 
Anticancer Res 2001 Mar-Apr;21(2A):873-8.

6. Jiang MC, Yang-Yen HF, Yen JJ, Lin JK. Curcumin induces 
apoptosis in immortalized NIH 3T3 and malignant cancer cell lines. Nutr 
Cancer 1996;26(1):111-20.

7. Huang MT, Newmark HL, Frenkel K. Inhibitory effects of 
curcumin on tumorigenesis in mice. J Cell Biochem Suppl 1997;27:26-34.

8. Limtrakul Pn P et al. Inhibition of carcinogen induced 
c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin. BMC Cancer 2001;1(1):1

9. Bielak-Zmijewska A et al. Effect of curcumin on the 
apoptosis of rodent and human nonproliferating and proliferating lymphoid cells. Nutr Cancer 2000;38(1):131-8.

10.Elattar TM, Virji AS. The inhibitory effect of curcumin, genistein, quercetin and cisplatin on the growth of oral cancer cells in vitro. 
Anticancer Res 2000 May-Jun;20(3a):1733-8.

11.Punithavathi D, Venkatesan N, Babu M. Curcumin inhibition of bleomycin-induced pulmonary fibrosis in rats. Br J Pharmacol 2000 
Sep;131(2):169-72.

12.Verma SP, Goldin PR, Lin PS. The inhibition of the estrogenic effects of pesticides and environmental chemicals by curcumin and isoflavonoids. Environ Health Perspect 1998 Dec;106(12):807-12.

13.Arbiser JL et al. Curcumin is an in vivo inhibitor of 
angiogenesis. Mol Med 1998 Jun;4(6):376-83. 

14.Lin JK, Chen YC, Huang YT, Lin-Shiau SY. Suppression of 
protein kinase C and nuclear oncogene expression as possible molecular 
mechanisms of cancer chemoprevention by apigenin and curcumin. J Cell Biochem Suppl 1997;28-29:39-48.

15.Li JK, Lin-Shia SY. Mechanisms of cancer chemoprevention by curcumin. Proc Natl Sci Counc Repub China B 2001 Apr;25(2):59-66.

16.Rajakrishnan V et al. Neuroprotective role of curcumin 
from curcuma longa on ethanol-induced brain damage. Phytother Res 1999 
Nov;13(7):571-4.

17.Chuang SE, Cheng AL, Lin JK, Kuo ML. Inhibition by curcumin of
diethylnitrosamine-induced hepatic hyperplasia, inflammation, cellular gene products and cell-cycle-related proteins in rats. Food Chem Toxicol 2000 Nov;38(11):991-5.

18.Mazumder A et al. Inhibition of human immunodeficiency 
virus type-1 integrase by curcumin. Biochem Pharmacol 1995 Apr 18;49(8):1165-70.

19.Sui Z, Salto R, Li J, Craik C, Ortiz de Montellano PR. 
Inhibition of the HIV-1 and HIV-2 proteases by curcumin and curcumin boron complexes. Bioorg Med Chem 1993 Dec;1(6):415-22.

20.Ranjan D et al. Enhanced apoptosis mediates inhibition of EBV-transformed lymphoblastoid cell line proliferation by curcumin. J Surg Res 1999 Nov;87(1):1-5.

21.Sharma A, Gautam S, Jadhav SS. Spice extracts as dose-modifying factors in radiation inactivation of bacteria. J Agric Food Chem 2000 Apr;48(4): 1340-4. 


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