Breast cancer doesn’t typically become a deadly disease until
it metastasizes. Tumors that remain confined to the breast tissue can usually
be treated with relative ease by surgery, radiation, and/or anticancer drugs.
But once cancer cells metastasize, or spread, to other parts of the
body—forming satellite tumors in places like the lymph nodes, bones, liver,
lungs, and brain—tracking down and destroying every errant malignant cell may
be near impossible … and the chances of survival worsen considerably. No known
pharmaceutical drug effectively prevents breast cancer metastasis. However, new
research from the M.D. Anderson Cancer Center at the University of Texas in
Houston suggests that consuming adequate amounts of the common spice curcumin
may halt the spread of breast cancer in its tracks.1
Curcumin is the primary ingredient in turmeric (Curcuma
longa), the spice that gives curry its trademark yellow color and unique
flavor. Turmeric has been used for millennia all over South Asia, not just for
flavoring foods but also for its medicinal properties. Perhaps not
coincidentally, epidemiologic data also suggest a relatively low rate of colon
cancer and other serious chronic diseases in South Asian countries.2
The new findings on breast cancer metastasis come from a study
in mice with breast tumors that were allowed to grow to about 10 mm in diameter
(about the size of a pea) before being surgically removed. Most such tumors
will have metastasized by the time of the surgery. The mice were then started
on a standard diet (control), or one of three experimental diets that included
either 1) powdered curcumin; 2) Taxol™ (paclitaxel),
a common breast cancer chemotherapy drug; or 3) curcumin + Taxol. Although
Taxol (like other conventional chemotherapy agents) normally suppresses breast
cancer growth in the short term, extended use can paradoxically increase the
risk of metastasis.
Breast cancer in mice typically spreads to the lungs. As shown in Figure 1, the
researchers later noted metastases visible to the naked eye in 96% of the mice
on the control diet, while Taxol alone produced only a modest reduction in lung
metastases. By contrast, in the mice treated with curcumin and especially
curcumin + Taxol, the incidence and number of visible lung metastases was
significantly reduced.
While it might be easy to dismiss this admittedly early finding
as merely suggestive and not necessarily clinically important (Of course,
clinical confirmation would certainly be extremely valuable!), many other
studies, both in the laboratory and the clinic, have convincingly demonstrated
that curcumin has important and wide-ranging anticancer benefits. For example,
curcumin has been shown to suppress the growth of cancer of the colon and rectum,2-6
prostate,7-15 breast,1, 16-20
lung,21-24 liver,25, 26 stomach,27,
28 bladder,29 and ovary.30
Thus, we have every reason to believe that these significant results, though
reported only so far in mice, would likely translate to a comparable benefit in
humans.
Multidimensional Anticancer Activities
Unlike most conventional chemotherapy agents, including Taxol,
curcumin’s anticancer actions appear to be multidimensional. Curcumin has well
known anti-inflammatory and antioxidant actions, both of which come into play
when facing a cancer. Curcumin’s inhibition of breast cancer metastasis in the
new mouse study appears to rest on its ability to suppress a substance called nuclear
factor kappa B (NF-?B),
which mediates cancer cell survival, proliferation, invasion, and metastasis:
the higher the level of NF-?B, the greater the risk of tumor growth and
metastasis.
Most chemotherapeutic agents, including Taxol, activate NF-?B,
which can actually make them procarcinogenic in the long run. On the
other hand, curcumin suppresses NF-?B activity.1 In the
animals treated with Taxol, curcumin also suppressed several procarcinogenic
enzymes, which are increased by this chemotherapeutic agent: cyclo-oxygenase 2
(COX 2), an enzyme associated with inflammation and cancer cell
proliferation; and matrix metalloproteinase-9, which is
thought to facilitate metastasis. Curcumin also fights cancer by inhibiting
cytochrome P-450 activity and increasing levels of glutathione-S-transferase.2
In addition to suppressing these enzymes, other studies have
demonstrated a wide variety of anticancer actions of curcumin. These include:
-
Promotion of apoptosis. Apoptosis is a kind of cellular suicide
that occurs normally in order to make way for new cells and also to remove
cells whose DNA has been damaged to the point at which cancerous change is
liable to occur. Anything that suppresses apoptosis – like NF-?B activity
triggered by Taxol and other agents – can promote cancer growth and metastasis.
By inducing apoptosis, curcumin prevents cancer growth and spread.8, 10, 16,
19, 23, 27, 31-33
-
Potentiating the effects of other forms of chemotherapy. By
blocking many of the procarcinogenic effects of conventional chemo- and
radiation therapy, curcumin helps reduce some of the dose-limiting adverse
effects of these agents, thus permitting higher doses to be used. This can
result in a synergistic effect of the combination of curcumin and conventional
chemotherapy. Combining curcumin and other natural therapies, such as
the soy isoflavones genistein and daidzein, also appears to have synergistic effects.1,
6, 7, 13, 20
-
Inhibiting angiogenesis. In order for tumors to thrive, blood
vessels must grow to support them, a process called angiogenesis. Curcumin
has been shown to inhibit angiogenesis, thus starving cancer cells of the vital
nutrients they need to survive.10, 12, 34-36
-
Inhibiting acquisition of “bone-like” properties. Prostate cancer
has a propensity to spread to bone, thanks at least in part to the ability of
malignant prostate cells to morph into bone-like cells. This osteomimetic
ability, which allows these cells to thrive in the bony microenvironment, is
blocked by curcumin.9
-
Disruption of cellular reproduction. At its basic level, cancer
is a disease of cellular reproduction (mitosis). Studies indicate that curcumin
interferes with mitosis and DNA expression in cancer cells in a variety of
ways, thus arresting the proliferation of malignant cells.12, 17, 37
How Much Curcumin Is Enough?
Although the vast majority of studies assessing the anticancer
properties of curcumin have been done in vitro (test tube) or in vivo
(lab animals), there is little doubt that most of these actions should work in
humans as well. The question is, how much do you have to ingest to produce a
clinical effect? Only a couple of trials have attempted to answer this
question. In one study, patients with colorectal cancer ingested curcumin
capsules containing from 450 mg to 3,600 mg (3.6 g) per day for 7
days.3
The results suggested that the 3.6-g dose produced levels in the colorectum
that were considered high enough to provide a therapeutic effect.
In another well-controlled clinical trial,38
patients with various high-risk premalignant lesions took curcumin for 3 months
at daily doses ranging from 1 g to 12 g. Improvement in the lesions was noted
in one of two patients with recently resected bladder cancer; two of seven
patients with oral leukoplakia (a precancerous condition of the mouth commonly
seen in long-time smokers); one of six patients with intestinal metaplasia of
the stomach (a precancerous condition of the stomach lining); one of four
patients with uterine cervical intraepithelial neoplasm, CIN, (a precancerous
condition of the uterine cervix); and two of six patients with Bowen’s disease
(a form of skin cancer caused by exposure to arsenic compounds). Most
important, there was absolutely no toxicity in these patients at doses up to 8
g per day. While the 12-g dose
was also nontoxic, it was deemed unacceptable because the volume of curcumin
was so large.
While the preliminary findings are extremely promising, clearly much more needs
to be done before we have a really clear understanding of the value and optimal
use of curcumin for treating or preventing cancer. Nevertheless, as noted
earlier, people in South Asia, who safely consume large amounts of
turmeric-containing curry dishes, have a low incidence of certain cancers (as
well as Alzheimer’s disease).
Given the absence of toxicity, there would seem to be no reason not to take
curcumin supplements (in addition to increasing your curry intake). Although
the studies cited above suggest doses of 3.6 g to 8 g per day, these studies
were done in people with active cancer or precancerous lesions.
The scientific researchers
Durk Pearson & Sandy Shaw suggest that healthy people would do well to
take 200 mg per day and to take it in its whole form, as turmeric.
They think this is a better idea, because turmeric contains other closely
related compounds that are even more effective than curcumin alone. The
efficacy of these active compounds ranges from 2-fold
to as much as 10- to 15-fold more effective. So while taking curcumin alone as
a preventive for cancer (or for Alzheimer’s) may well help, taking the entire
turmeric package may work even better, because it contains more powerful
antioxidants that have evolved together to work more effectively.
References
-
Aggarwal BB, Shishodia S, Takada Y, et al. Curcumin suppresses the
paclitaxel-induced nuclear factor-?B pathway in breast cancer cells and
inhibits lung metastasis of human breast cancer in nude mice. Clin Cancer Res.
2005;11:7490-7498.
-
Chauhan DP. Chemotherapeutic potential of curcumin for colorectal cancer. Curr
Pharm Des.
2002;8:1695-1706.
-
Garcea G, Berry DP, Jones DJ, et al. Consumption of the putative
chemopreventive agent curcumin by cancer patients: Assessment of curcumin
levels in the colorectum and their pharmacodynamic consequences. Cancer
Epidemiol Biomarkers Prev.
2005;14:120-125.
-
Kawamori T, Lubet R, Steele VE, et al. Chemopreventive effect of curcumin, a
naturally occurring anti-inflammatory agent, during the promotion/progression
stages of colon cancer. Cancer Res.
1999;59:597-601.
-
Kim KH, Park HY, Nam JH, et al. [the inhibitory effect of curcumin on the
growth of human colon cancer cells (HT-29, WiDr) in vitro]. Korean J
Gastroenterol.
2005;45:277-284.
-
Narayan S. Curcumin, a multi-functional chemopreventive agent, blocks growth of
colon cancer cells by targeting beta-catenin-mediated transactivation and
cell-cell adhesion pathways. J Mol Histol.
2004;35:301-307.
-
Chendil D, Ranga RS, Meigooni D, Sathishkumar S, Ahmed MM. Curcumin confers
radiosensitizing effect in prostate cancer cell line PC-3. Oncogene.
2004;23:1599-1607.
-
Deeb D, Jiang H, Gao X, et al. Curcumin sensitizes prostate cancer cells to
tumor necrosis factor-related apoptosis-inducing ligand/Apo2L by inhibiting
nuclear factor-?B through suppression of IkappaBalpha phosphorylation. Mol Cancer Ther.
2004;3:803-812.
-
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;4:1-6.
-
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;47:293-303.
-
Dorai T, Dutcher JP, Dempster DW, Wiernik PH. Therapeutic potential of curcumin
in prostate cancer V. Interference with the osteomimetic properties of hormone
refractory C4-2B prostate cancer cells. Prostate.
2004;60:1-17.
-
Holy J. Curcumin inhibits cell motility and alters microfilament organization
and function in prostate cancer cells. Cell Motil Cytoskeleton.
2004;58:253-268.
-
Hour TC, Chen J, Huang CY, Guan JY, Lu SH, Pu YS. Curcumin enhances
cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing
p21(WAF1/CIP1) and C/EBPbeta expressions and suppressing NF-?B activation. Prostate.
2002;51:211-218.
-
Mukhopadhyay A, Bueso-Ramos C, Chatterjee D, Pantazis P, Aggarwal BB. Curcumin
downregulates cell survival mechanisms in human prostate cancer cell lines. Oncogene.
2001;20:7597-7609.
-
Nakamura K, Yasunaga Y, Segawa T, et al. Curcumin down-regulates AR gene
expression and activation in prostate cancer cell lines. Int J Oncol.
2002;21:825-830.
-
Choudhuri T, Pal S, Agwarwal ML, Das T, Sa G. Curcumin induces apoptosis in
human breast cancer cells through p53-dependent Bax induction. FEBS Lett.
2002;512:334-340.
-
Holy JM. Curcumin disrupts mitotic spindle structure and induces
micronucleation in MCF-7 breast cancer cells. Mutat Res.
2002;518:71-84.
-
Ramachandran C, Fonseca HB, Jhabvala P, Escalon EA, Melnick SJ. Curcumin
inhibits telomerase activity through human telomerase reverse transcriptase in
MCF-7 breast cancer cell line. Cancer Lett.
2002;184:1-6.
-
Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. Dietary
curcumin inhibits chemotherapy-induced apoptosis in models of human breast
cancer. Cancer Res.
2002;62:3868-3875.
-
Verma SP, Salamone E, Goldin B. Curcumin and genistein, plant natural products,
show synergistic inhibitory effects on the growth of human breast cancer MCF-7
cells induced by estrogenic pesticides. Biochem Biophys Res Commun.
1997;233:692-696.
-
Chen YS, Ho CC, Cheng KC, et al. Curcumin inhibited the arylamines
n-acetyltransferase activity, gene expression and DNA adduct formation in human
lung cancer cells (A549). Toxicol In Vitro.
2003;17:323-333.
-
Chen HW, Yu SL, Chen JJ, et al. Anti-invasive gene expression profile of
curcumin in lung adenocarcinoma based on a high throughput microarray analysis. Mol
Pharmacol.
2004;65:99-110.
-
Radhakrishna Pillai G, Srivastava AS, Hassanein TI, Chauhan DP, Carrier E.
Induction of apoptosis in human lung cancer cells by curcumin. Cancer Lett.
2004;208:163-170.
-
Zhang J, Qi H, Wu C. [research of anti-proliferation of curcumin on a549 human
lung cancer cells and its mechanism]. Zhong Yao Cai.
2004;27:923-927.
-
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;38:991-995.
-
Notarbartolo M, Poma P, Perri D, Dusonchet L, Cervello M, D'Alessandro N.
Antitumor effects of curcumin, alone or in combination with cisplatin or
doxorubicin, on human hepatic cancer cells. Analysis of their possible
relationship to changes in NF-?B activation levels and in IAP gene expression. Cancer
Lett.
2005;224:53-65.
-
Moragoda L, Jaszewski R, Majumdar AP. Curcumin induced modulation of cell cycle
and apoptosis in gastric and colon cancer cells. Anticancer Res.
2001;21:873-878.
-
Swarnakar S, Ganguly K, Kundu P, Banerjee A, Maity P, Sharma AV. Curcumin
regulates expression and activity of matrix metalloproteinases-9 and -2
during prevention and healing of indomethacin-induced gastric ulcer. J Biol
Chem.
2004.
-
Sun M, Yang Y, Li H, et al. [the effect of curcumin on bladder cancer cell line
EJ in vitro]. Zhong Yao Cai.
2004;27:848-850.
-
Zheng L, Tong Q, Wu C. Growth-inhibitory effects of curcumin on ovary cancer
cells and its mechanisms. J Huazhong Univ Sci Technolog Med Sci.
2004;24:55-58.
-
Jiang MC, Yang-Yen HF, Yen JJ, Lin JK. Curcumin induces apoptosis in
immortalized NIH 3T3 and malignant cancer cell lines. Nutr Cancer.
1996;26:111-120.
-
Karunagaran D, Rashmi R, Kumar TR. Induction of apoptosis by curcumin and its
implications for cancer therapy. Curr Cancer Drug Targets.
2005;5:117-129.
-
Rashmi R, Santhosh Kumar TR, Karunagaran D. Human colon cancer cells differ in
their sensitivity to curcumin-induced apoptosis and heat shock protects them by
inhibiting the release of apoptosis-inducing factor and caspases. FEBS Lett.
2003;538:19-24.
-
Adams BK, Ferstl EM, Davis MC, et al. Synthesis and biological evaluation of
novel curcumin analogs as anti-cancer and anti-angiogenesis agents. Bioorg Med
Chem.
2004;12:3871-3883.
-
Gao C, Ding Z, Liang B, Chen N, Cheng D. [study on the effects of curcumin on
angiogenesis]. Zhong Yao Cai.
2003;26:499-502.
-
Hahm ER, Gho YS, Park S, Park C, Kim KW, Yang CH. Synthetic curcumin analogs
inhibit activator protein-1 transcription and tumor-induced
angiogenesis. Biochem Biophys Res Commun.
2004;321:337-344.
-
Lin JK. Suppression of protein kinase c and nuclear oncogene expression as
possible action mechanisms of cancer chemoprevention by curcumin. Arch Pharm
Res.
2004;27:683-692.
-
Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a
chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer
Res. 2001;21:2895-2900.
|