Abstract
BackgroundPancreatic 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.MethodsCCK-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.ResultsSophoridine 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.ConclusionThese findings suggest Sophoridine is promising to be a novel, potent and selective antitumor drug candidate for pancreatic cancer.
Highlights
Pancreatic cancer is generally acknowledged as the most common primary malignant tumor, and it is known to be resistant to conventional chemotherapy
Sophoridine shows an extensive tumor-killing effects and exhibits the most potent cytotoxicity to pancreatic cancer cells Sophoridine is a monomeric alkaloid extracted from sophora alopecuroides L (Fig. 1a)
We found that Sophoridine treatment substantially activated ERK and JNK in pancreatic cancer cells, and the phosphorylation levels were dependent on reactive oxygen species (ROS) levels, supporting by the data that the activation was abrogated by addition of NAC
Summary
Pancreatic cancer is generally acknowledged as the most common primary malignant tumor, and it is known to be resistant to conventional chemotherapy. Pancreatic cancer is still one of the deadliest solid malignancies across the world at present. It has the poorest prognosis of any major tumor type, with a pretty low 5-year survival rate of approximately 5% for decades [1,2,3]. The severe drug resistance, including intrinsic and acquired, is thought to be responsible for the limited the therapeutic efficacy. New effective treatments and drugs are urgently needed in order to improve the clinical outcome of pancreatic cancer patients. Traditional herbal agents, containing various biologically active natural compounds, are claimed to have impressive therapeutic efficacy with minimal adverse effects, which
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