Antiproliferative effects of curcumin analog L49H37 in pancreatic stellate cells: a comparative study

Background: Pancreatic cancer is a devastating disease with poor prognosis. It is characterized by a pronounced stromal reaction, which resists chemotherapeutics and effective tumor treatment. Pancreatic stellate cells (PSCs) are mainly responsible for this stromal reaction. Moreover, the cancer and stromal interaction seems to promote tumor proliferation. In this study, L49H37, a newly synthesized curcumin analog, was used as intervention to target the stromal compartment of pancreatic cancer.

Methods: In vitro cultures of human PSCs were exposed to curcumin and L49H37. Cell viability as well as growth promoting and survival signaling pathways were monitored by MTT, flow cytometry and western blotting.

Results: Curcumin and L49H37 effectively inhibited proliferation and induced apoptosis in PSCs. L49H37 was found to be more potent at a lower concentration than curcumin in the induction of apoptosis, as evidenced by cleaved poly (ADP-ribose) polymerase (PARP). The cells were retained in the G0/G1 phase of the cell cycle through the downregulation of p21^WAF1/Cip1. L49H37 significantly decreased the phosphorylation of extracellular signal regulated kinase ½ (ERK½).

Conclusion: The results indicate that curcumin analog L49H37 exhibits more potent inhibitory effects than curcumin itself at a lower concentration, which suggests that it may have a potential for further evaluation of its use against pancreatic adenocarcinoma, either as a single agent but, more probable, as part of a combination regimen.