Re: In Vitro and In Vivo Studies Indicate Curcumin Potential for Preventing and/or Treating Colorectal Cancer
Kunnumakkara AB, Guha S, Aggarwal BB. Curcumin and colorectal cancer: add spice to your life. Curr Colorectal Cancer Rep. 2009;5: 5-14.
found from 3% to 5% in turmeric (Curcuma
longa), is the major active component of this medicinal spice used in curry
powder, an integral part of Indian cooking and lifestyle. Epidemiological
studies have found that colorectal cancer is less prevalent in Eastern nations,
including India (30 cases
per million), where turmeric is regularly consumed, than in Western countries,
including the U.S.
(530 cases per million). The authors summarize data indicating that turmeric
and curcumin may exercise protective effects specifically against colorectal
curcumin, turmeric and commercial curcumin contains demethoxycurcumin and bisdemethoxycurcumin
(around 17% and 3%, respectively, together with about 77% curcumin in
commercial concentrates). While curcumin is considered the most active ingredient,
it may be that complete turmeric is more potent than any single component.
Compounds found in turmeric are chemically similar to those found in other
medicinal plants, such as gingerol in ginger (Zingiber officinale), yakuchinone-A in Chinese galangal (Alpinia chinensis), and iso-eugenol in
clove (Syzygium aromaticum).
molecular targets of curcumin in colon cancer are discussed, including
inhibition of nuclear factor kB signaling, activation of
peroxisome proliferator-activated receptor-g in colon cancer cells, inhibition of the
transcription factor early growth response-1, inhibition of β-catenin signaling,
and inhibition of mitogen-activated protein kinases. Curcumin also inhibits
cyclin-dependent kinases, blocks epidermal growth factor receptor signaling,
carcinogen transformation, and inhibits inflammatory COX-2 and 5-LOX expression
in mouse tumors. Studies have found that curcumin induces the tumor suppressor p53,
inhibits B-cell lymphoma-2 and basal cell lymphoma-extra large in xenograft
tumors in mice, inhibits the proinflammatory cytokine interleukin-8, and
mediates ceramide generation and apoptosis in colon cancer cells. These molecular-level
effects on cellular activity suppress proliferation, inhibit cell growth,
reduce biotransformational enzymes, control DNA damage, inhibit cancer cell
cycle progression, reduce cancer cell survival, promote cancer cell apoptosis, and
block cancer cell migration.
vitro studies show that curcumin suppresses proliferation and increases
apoptosis in several colorectal cancer lines. At least 8 rodent studies have
found that ingested curcumin prevents colon cancer growth, and 2 studies showed
it was an effective therapy in colon and colorectal cancers in mice.
to both standard chemotherapeutic drugs and radiotherapy is a serious problem
in colorectal cancer treatment. Studies have found that curcumin sensitizes
cancer cells to such treatments in mice.
and systemic bioavailability of curcumin are low, but for gastrointestinal
diseases this is not a problem. Turmeric extract or curcumin must be consumed
in rather large quantities to be useful. It is most effective in its cancer prevention
and reduction activities in the gastrointestinal tract, and is believed to be
metabolized in the intestines. Curcumin conjugation is much more extensive in
intestinal fractions from humans than those from rats, but less extensive in
human hepatic fractions than those from rats. The curcumin-reducing capacity of
cytosol from human intestinal and liver tissue was greater than in
corresponding rodent tissue by factors of 18 and 5, respectively. Results
demonstrate that human intestinal tissue has more curcumin metabolites than rat
intestinal tissue. Curcumin has been studied for toxicity in rodents; no
toxicity was found, but dose-dependent increases in liver weight were observed in
rats receiving curcumin versus controls. In humans, no toxicity has been found
in doses up to 12 g daily.
A number of
human clinical trials with curcumin have been conducted. Positive results have
been achieved in some, indicating that curcumin may be useful in inhibiting
expression of familial adenomatous polyposis and in treating ulcerative
proctitis, Crohn's disease, and ulcerative colitis; and turmeric extract daily
for 8 weeks helped in reducing symptoms of irritable bowel syndrome.
patients with advanced colorectal cancer refractory to standard chemotherapy,
ingestion of turmeric extract for 4 months showed radiological stable disease
for 2 to 4 months in 5 patients. No dose-limiting toxicity was observed. Other
studies have also reported limited results, perhaps a function of study design
and limited objectives. In the authors' own study of pancreatic cancer, 25
patients received 8 g curcumin for two months; of 21 available for response,
two had clinical biological activity, one was stabilized for over 18 months,
and one had a brief but marked (73%) tumor regression. The authors state that
due to its potent anti-inflammatory activity, "curcumin has potential for
preventing and treating CRC" (colorectal cancer), though more studies are
needed to assess this potential.