Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines

Abstract

Pancreatic cancer is the fourth leading cause of cancer death. Gemcitabine is widely used as a chemotherapeutic agent for the treatment of pancreatic cancer, but the prognosis is still poor. Berberine, an isoquinoline alkaloid extracted from a variety of natural herbs, possesses a variety of pharmacological properties including anticancer effects. In this study, we investigated the anticancer effects of berberine and compared its use with that of gemcitabine in the pancreatic cancer cell lines PANC-1 and MIA-PaCa2. Berberine inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. After berberine treatment, the G1 phase of PANC-1 cells increased by 10% compared to control cells, and the G1 phase of MIA-PaCa2 cells was increased by 2%. Whereas gemcitabine exerts antiproliferation effects through S-phase arrest, our results showed that berberine inhibited proliferation by inducing G1-phase arrest. Berberine-induced apoptosis of PANC-1 and MIA-PaCa2 cells increased by 7 and 2% compared to control cells, respectively. Notably, berberine had a greater apoptotic effect in PANC-1 cells than gemcitabine. Upon treatment of PANC-1 and MIA-PaCa2 with berberine at a half-maximal inhibitory concentration (IC50), apoptosis was induced by a mechanism that involved the production of reactive oxygen species (ROS) rather than caspase 3/7 activation. Our findings showed that berberine had anti-cancer effects and may be an effective drug for pancreatic cancer chemotherapy.

Berberine and barberry (Berberis vulgaris): A clinical review

“…Berberine induces reactive oxygen species (ROS) production and activates mitochondriadependent apoptosis in prostate cancer cells (Meeran, Katiyar, & Katiyar, 2008). It also induced ROS-mediated cell death and apoptosis in pancreatic, breast, and colon cancer through activation of apoptosis-inducing factor (Park, Sung, Kim, & Chung, 2015;Wang et al, 2012;Xie et al, 2015). Herbal medicines appear to be possible candidates for treatment of cerebral ischemia (Behravan, Razavi, & Hosseinzadeh, 2014).…”

Targeting reactive oxygen species in development and progression of pancreatic cancer

“…In this setting, the anti-oncogenic effects of nimbolide were mediated through the generation of excessive ROS and induction of autophagy and apoptosis [141]. Other naturally derived compounds like berberine and isoalantolactone have also demonstrated anti-cancer activity in PDA cells in vitro in a manner which is dependent on enhanced ROS production [142,143]. …”

Berberine Induces Cell Cycle Arrest in Cholangiocarcinoma Cell Lines <i>via</i> Inhibition of NF-κB and STAT3 Pathways

“…The strong anti-tumor growth via induction of cell cycle arrest, apoptosis and inhibition of metastasis have been shown in several in vitro and in vivo studies. [6][7][8] Little, however, is known about the anti-cancer activities of berberine on CCA. The present work was aimed to determine the anti-cancer activities and potential molecular mechanisms of berberine on CCA cell lines.…”