Curcumin, an ingredient in the dietary spice turmeric (see box), may be useful in treating pancreatic cancer, according to two groups of investigators who presented their work at the Society for Integrative Oncology Third International Conference.
BOSTONCurcumin, an ingredient in the dietary spice turmeric (see box), may be useful in treating pancreatic cancer, according to two groups of investigators who presented their work at the Society for Integrative Oncology Third International Conference.
Shahar Lev-Ari, PhD, of Tel Aviv University, Israel, discussed preclinical findings with curcumin and gemcitabine (Gemzar) in pancreatic cell lines (abstract C013), and Navneet Dhillon, MD, of M.D. Anderson Cancer Center, reported on a phase II trial using curcumin in patients (abstract D025).
Since inhibition of COX2 has proven to be a productive route for cancer prevention, Dr. Lev-Ari set out to test the ability of curcumin to inhibit COX2 activity in two pancreatic cell lines: p34, which produces high levels of COX2, and Panc-1, a low-COX2-expressing line.
When exposed to increasing concentrations of curcumin, both cell lines showed inhibition of COX2 expression in a dose-dependent manner, but the effect was much stronger on the p34 cell line. Curcumin also induced apoptosis in a dose-dependent manner in the p34 line. When the cells were exposed to both curcumin and gemcitabine, curcumin increased the inhibitory effect of gemcitabine on cell growth, as well as apoptotic activity, in p34 but not Panc-1 cells.
Effects on Cell Cycle
Dr. Lev-Ari and his colleagues discovered that curcumin affected the cell cycle of p34 cells by causing G2/M arrest, but had no effect on the Panc-1 cell cycle. Curcumin also downregulated both COX2 and EGFR in a dose-dependent manner in COX2-positive cell lines.
"Since most pancreatic tumors have high COX2 levels, it seems possible that combining curcumin, which has a strong effect on COX2 levels in preclinical studies, with gemcitabine may prove to be a promising strategy for pancreatic cancer patients," Dr. Lev-Ari said. Clinical trials in pancreatic cancer patients using both agents are being planned.
Phase II Trial
Scientists at M.D. Anderson Cancer Center are currently recruiting 50 patients with unresectable or metastatic pancreatic cancer for a phase II trial of curcumin. "Patients receive 8 g by mouth daily until progression by radiographical clinical evaluation," Dr. Dhillon said. "So far, 25 have enrolled; 24 have been evaluated for toxicity and 21 for response." Dr. Dhillon presented the results on behalf of study chair Razelle Kurzrock, MD.
Preliminary findings show that two patients have had stable disease for more than 6 months, and one patient had a 73% reduction in tumor size that was, however, short lived (1 month). No toxicities have been observed. Four patients, including the one with tumor regression, had marked increases (2- to 35-fold) in levels of serum IL-1 receptor antagonist, IL-6, IL-10, and IL-8.
"For now, we can conclude that curcumin is well tolerated, and our preliminary results suggest that curcumin has biologic activity in pancreatic cancer," Dr. Dhillon commented. The trial is expected to end around June 2007.