Bharangin, A Diterpenoid, Enhances the Sensitivity of Pancreatic Cancer Cells to Gemcitabine Through Involvement of Long Non‐Coding RNAs and Nuclear Factor‐κB

Pancreatic cancer (PaCa) manifests as an aggressive tumour due to the late occurrence of early symptoms. The overall 5-year survival rate of PaCa is merely 2%-9%. Bharangin (BG), a diterpenoid quinonemethide known for its anti-cancer activities, was investigated in a preclinical PaCa model. A dose- and time-dependent suppression in the viability of PaCa cells was observed by BG. The diterpenoid suppressed the level of tumorigenic proteins in PaCa cells. As evident from phosphatidylserine externalisation, acridine orange (AO)/propidium iodide (PI) staining, cell cycle analysis and DNA laddering, BG was found to induce apoptosis in PaCa cells. An accumulation in the sub-G1 population was observed by BG. The diterpenoid induced depolarization in the mitochondrial membrane potential and enhanced the PaCa cells' sensitivity to gemcitabine (GEM). The cancer-associated lncRNAs were also modulated by both BG and GEM in PaCa cells. BG also suppressed the p65 nuclear translocation induced by TNF-α in PaCa cells. Overall, BG exhibits activities in PaCa cells. The suppression of NF-κB activation and the modulation of lncRNAs expression may provide a basis for further exploration of BG as a therapeutic agent in PaCa.