Caudatin targets TNFAIP1/NF-κB and cytochrome c/caspase signaling to suppress tumor progression in human uterine cancer

Tan,Zhi-Wen; Xie,Shun; Hu,Si-Yang; Liao,Tao; Liu,Pan; Peng,Ke-Hong; Yang,Xin-Zhou; He,Zhi-Li; Tang,Hong-Yan; Cui,Yuan; Peng,Xiao-Ning; Zhang,Jian; Zhou,Chang

doi:10.3892/ijo.2016.3662

Caudatin targets TNFAIP1/NF-κB and cytochrome c/caspase signaling to suppress tumor progression in human uterine cancer

Authors:
- Zhi-Wen Tan
- Shun Xie
- Si-Yang Hu
- Tao Liao
- Pan Liu
- Ke-Hong Peng
- Xin-Zhou Yang
- Zhi-Li He
- Hong-Yan Tang
- Yuan Cui
- Xiao-Ning Peng
- Jian Zhang
- Chang Zhou
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Affiliations: Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China, Department of Gynecological Oncology, Hunan Cancer Hospital, Changsha, Hunan 410013, P.R. China, College of Medicine, Hunan Normal University, Changsha, Hunan 410013, P.R. China
Published online on: August 19, 2016 https://doi.org/10.3892/ijo.2016.3662
Pages: 1638-1650

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Abstract

Caudatin, a C-21 steroidal glycoside isolated from Chinese herbs, has a long history of use for the treatment of multiple diseases, including cancers. However, the precise mechanisms of actions of caudatin in human uterine cancer cells remain unclear. In this study, we investigated the molecular mechanisms by which caudatin inhibits cell growth in human cervical carcinoma cell line (HeLa) and endometrial carcinoma cell line (HEC-1A). Treatment with caudatin promoted cell morphology change, inhibited cell proliferation, colony formation, migration and spheroid formation, and induced cell apoptosis. Our results showed that the expression of tumor necrosis factor; α-induced protein 1 (TNFAIP1) was downregulated in uterine cancer cells and tissues compared to paired adjacent non-tumor uterine tissues. Further molecular mechanism study showed that caudatin can directly regulate TNFAIP1 expression in a concentration-dependent manner and also associated with the downregulation of NF-κB and upregulation of BAX/BcL-2 ratio and caspase-3. Moreover, we found that overexpression of TNFAIP1 inhibits the growth and invasion, and induces apoptosis in uterine cancer cells through inhibition of the NF-κB pathway, suggesting that TNFAIP1 may act as a potential therapeutic target for the treatment of cancer. We found that caudatin inhibited tumorigenicity and upregulated TNFAIP1 in vivo. Taken together, caudatin impacts on cell proliferation, migration and apoptosis of uterine cancer cells by regulating several carcinogenesis-related processes, including a novel mechanism involving the targeting of TNFAIP1/NF-κB signaling. Our findings provide new insights into understanding the anticancer mechanisms of caudatin in human uterine cancer therapy.

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