5-year survival for pancreatic cancer (PanCA) continuous to be lower than any other solid tumor due to late stage diagnosis combined with lack of effective therapeutic options. Therefore developing novel strategies possibly based on molecular targets is critical for successful management of PanCA. Recent studies from our laboratory show potential anti-pancreatic cancer activity for NexrutineR (Nx), a bark extract isolated from traditional Chinese medicine Phellodendron amurense. These studies also show that Nx reduces pancreatic fibrosis in preclinical animal model through targeting two critical oncogenic transcription factors including NF-κB and Stat3. Nonetheless, the precise molecular mechanism associated with the observed biological activity is unclear. We investigated whether Nx inhibits pancreatic cell proliferation and pancreatic fibrosis via reactive oxygen species (ROS)-mediated activation of autophagy. Our data show that Nx can induce autophagy at earlier time points (4h) but inhibit autophagy at later time points (24h) in human pancreatic cancer cell lines Capan-2 and BxPC-3 as evidenced by autophagosome formation, alteration in the expression and levels of various autophagy related genes. Interestingly Nx also induced apoptosis at 24h time point but not at 4h suggesting that autophagy precedes apoptosis. Further under these experimental conditions, treatment of pancreatic cancer cells with Nx enhanced intracellular production of ROS implicating a cross talk between Nx-induced ROS, autophagy and apoptosis. Overall, our findings divulge an important role for ROS/autophagy/apoptosis in Nx-mediated anti-pancreatic cancer effects. Supported by NCCAM (APK).

Citation Format: Gong Jingjing, Addanki P. Kumar. Therapeutic targeting cross talk between ROS/autophagy and apoptosis for pancreatic cancer by a herbal extract. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1660. doi:10.1158/1538-7445.AM2013-1660