Sophoridine induces apoptosis and S phase arrest via ROS-dependent JNK and ERK activation in human pancreatic cancer cells

Abstract

Background

Pancreatic cancer is generally acknowledged as the most common primary malignant tumor, and it is known to be resistant to conventional chemotherapy. Novel, selective antitumor agents are pressingly needed.

Methods

CCK-8 and colony formation assay were used to investigate the cell growth. Flow cytometry analysis was used to evaluate the cell cycle and cell apoptosis. The peroxide-sensitive fluorescent probe DCFH-DA was used to measure the intracellular ROS levels. Western blot assay was used to detect the levels of cell cycle and apoptosis related proteins. Xenografts in nude mice were used to evaluate the effect of Sophoridine on pancreatic cancer cell in vivo.

Results

Sophoridine killed cancer cells but had low cytotoxicity to normal cells. Pancreatic cancer cells were particularly sensitive. Sophoridine inhibited the proliferation of pancreatic cancer cells and induced cell cycle arrest at S phase and mitochondrial-related apoptosis. Moreover, Sophoridine induced a sustained activation of the phosphorylation of ERK and JNK. In addition, Sophoridine provoked the generation of reactive oxygen species (ROS) in pancreatic cancer cells. Finally, in vivo, Sophoridine suppressed tumor growth in mouse xenograft models.

Conclusion

These findings suggest Sophoridine is promising to be a novel, potent and selective antitumor drug candidate for pancreatic cancer.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jkezkK