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Abstract Title:

Rheumatoid arthritis drug sinomenine induces apoptosis of cervical tumor cells by targeting thioredoxin reductase in vitro and in vivo.

Abstract Source:

Bioorg Chem. 2022 May ;122:105711. Epub 2022 Feb 28. PMID: 35247807

Abstract Author(s):

Dongzhu Duan, Yanru Wang, Dabo Pan, Xiaojie Jin, Yunyun Yan, Peng Song, Le Wang, Jian Xiao, Zihua Wang, Xiaoling Wang

Article Affiliation:

Dongzhu Duan

Abstract:

Overexpression of thioredoxin reductase (TrxR) has been linked to tumorigenesis and phenotypic maintenance of malignant tumors. Thus, targeting TrxR with natural molecules is a promising strategy for developing anticancer drugs. Sinomenine is a naturally occurring alkaloid isolated from Sinomenium acutum. The drug, Zhengqing Fengtongning made from sinomenine, has been universally applied in rheumatoid arthritis treatment in China as well as other Asian countries for decades. Recently, increasing evidence indicates that sinomenine appears to be a promising therapeutic agent against various cancer cells. However, the exact mechanism underlying the anticancer activity of sinomenine remains unclear. In this study, we identified sinomenine as a kind of new inhibitor for TrxR. Pharmacological inhibition of TrxR by sinomenine results in the decrease of thiols content, increases the levels of reactive oxygen species, and finally facilitates oxidative stress-mediated cancer cell apoptosis. It is vital that knockdown in TrxR1 by shRNA can increase cell sensitivity to sinomenine. Treatment with sinomenine in vivo leads to a decrease in TrxR activity and tumor growth, and an increase in apoptosis. Our findings provide a novel action mechanism related to sinomenine and presents an insight on how to develop sinomenine as a chemotherapeutic agent for cancer therapy.

Study Type : In Vitro Study

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