J Cancer 2021; 12(1):270-280. doi:10.7150/jca.50360

Research Paper

Tephrosin induces apoptosis of human pancreatic cancer cells through the generation of reactive oxygen species

Jie Du1*, Fan Jiang1✉*, Shen-Sheng Xu1*, Zi-Feng Huang1, Li‐Li Chen1, Li Li2✉

1. Department of Hepatobiliary Surgery, the Affiliated Puren Hospital of Wuhan University of Science and Technology, Wuhan, China.
2. Department of Centre for clinical teaching skills, the Affiliated Puren Hospital of Wuhan University of Science and Technology, Wuhan, China.
*These authors contributed equally to this work.

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Citation:
Du J, Jiang F, Xu SS, Huang ZF, Chen L, Li L. Tephrosin induces apoptosis of human pancreatic cancer cells through the generation of reactive oxygen species. J Cancer 2021; 12(1):270-280. doi:10.7150/jca.50360. Available from https://www.jcancer.org/v12p0270.htm

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Abstract

Tephrosin is a natural rotenoid isoflavonoid that has been shown to have potent anticancer activities. In this study, we reported the anticancer activity of tephrosin against pancreatic cancer cells. Tephrosin potently suppressed cell viability in various cancer cell lines and promoted apoptosis of PANC-1 and SW1990 pancreatic cancer cells evidenced by enhanced cleavage of caspase-3/-9 and PARP. Further studies showed that tephrosin increased the production of intracellular reactive oxygen species (ROS) and led to mitochondrial membrane potential depolarization, and subsequent cytochrome c release. DNA damage was also identified by increased tail DNA and phosphorylation of H2AX. Intracellular ROS production seems to be essential for the anticancer activity of tephrosin, alleviation of ROS production by ROS scavengers weakened the apoptotic effects of tephrosin. Importantly, in PANC-1 xenografted nude mice, potent antitumor activity and low toxicity of tephrosin were observed. In conclusion, these results indicated that tephrosin could be developed as a potential chemotherapeutic agent for the treatment of human pancreatic cancer.

Keywords: Tephrosin, pancreatic cancer, reactive oxygen species, apoptosis