Zyflamend Induces Apoptosis in Pancreatic Cancer cells via Modulation of the JNK Pathway

Abstract

Current pharmacological therapies and treatments targeting pancreatic neuroendocrine tumors (PNETs) have proven ineffective, far too often. Therefore, there is an urgent need for alternative therapeutic approaches. Zyflamend, a combination of anti‐inflammatory herbal extracts, that has proven to be effective in various in vitro and in vivo cancer platforms, shows promise. However, its effects on pancreatic cancer, in particular, remain largely unexplored. Herein, we demonstrate that Zyflamend treatment decreased cell proliferation in a dose‐dependent manner, concomitant with increased apoptotic cell death and cell cycle arrest at the G2/M phase. At the molecular level, treatment with Zyflamend led to the induction of ER stress, autophagy, and the activation of c‐Jun N‐terminal kinase (JNK) pathway. Notably, pharmacological inhibition of JNK abrogated the pro‐apoptotic effects of Zyflamend. Furthermore, Zyflamend exacerbated the effects of streptozotocin and adriamycin‐induced ER stress, autophagy, and apoptosis. These studies identify Zyflamend as a potential novel approach to treat pancreatic cancer via modulation of the JNK pathway.Support or Funding InformationThis work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R00DK100736) to A.B.