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Curcumin May Enhance TRAIL-Induced Cancer Cell Death

Curcumin May Enhance TRAIL-Induced Cancer Cell Death

SAN FRANCISCO—Curcumin, the active ingredient in the spice turmeric, can
act together with the natural molecule TRAIL to increase apoptosis in
androgen-sensitive human prostate cancer cells, researchers said at the 93rd
Annual Meeting of the American Association for Cancer Research (abstract 4237).

"When added at low concentrations, neither agent alone produced
significant effects. But when added together, they induced apoptosis in 70% to
80% of LNCaP prostate cancer cells," said lead researcher Subhash C.
Gautam, PhD, senior staff investigator in the Department of Internal Medicine,
Division of Hematology and Oncology, Henry Ford Health System, Detroit.

Curcumin has long been used as a folklore remedy and anti-inflammatory
agent. Recent studies have revealed it is also an antioxidant and is
chemopreven-tive against several tumor cell lines, Dr. Gautam said. In India,
where it is used commonly to spice foods, there is a very low rate of
gastrointestinal tumors, especially colon cancers.

LNCaP, an androgen-sensitive human prostate cell line, is moderately
sensitive to the induction of apoptosis by TNF (tumor necrosis factor)-related
apoptosis-inducing ligand (TRAIL). In the study, the researchers aimed to find
out whether curcumin and TRAIL cooperatively interact to increase apoptosis in
this prostate cancer cell line. The researchers also sought to find the
mechanism by which TRAIL and curcumin could produce apoptosis.

The researchers found that low concentrations of either agent used alone (10 µM curcumin; 20 ng/mL TRAIL) did not have enough cytotoxicity to induce
significant apoptosis in the prostate cancer cell line. But when used together,
these two agents enhanced cell death by two- to threefold (see Figure).

The combined treatment induced DNA fragmentation in LNCaP cells. The
production of DNA fragments in treated LNCaP cells was associated with the
cleavage of procaspase-3 and poly (ADP-ribose) polymerase (PARP). Cells were
protected from dying in the presence of a general caspase inhibitor (zVAD-fmk)
or a caspase-3 specific inhibitor (zDEVD-fmk). These data indicate that
apoptosis is the major mode of tumor cell death induced by the combined
curcumin and TRAIL treatment, Dr. Gautam said.

Since the AACR meeting, the researchers have observed similar apoptosis with
combined curcumin and TRAIL treatment in neuroblastoma and glioma cell lines.
"This opens possibilities for patients who have become resistant to other
treatments," Dr. Gautam said. "Curcumin as an oral supplement might
sensitize drug-resistant tumors to immunotherapy with TRAIL." Although
TRAIL is effective at inducing apoptosis in tumors in vivo, it is toxic at
therapeutic levels.

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