Thiostrepton suppresses triple-negative breast cancer through downregulating c-FLIP/SMAD2/3 signaling pathway

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis of breast cancer. Thiostrepton exerts anti-tumor activities against several cancers including TNBC. Herein we discussed the new molecular mechanisms of thiostrepton in TNBC. Thiostrepton inhibited MDA-MB-231 cell viability, accompanied by a decrease of c-FLIP and p-SMAD2/3. c-FLIP overexpression reduced the sensitivity of MDA-MB-231 cells to thiostrepton, while SMAD2/3 knockdown increased the sensitivity of MDA-MB-231 cells to thiostrepton. Moreover, c-FLIP overexpression significantly increased the expression and phosphorylation of SMAD2/3 proteins and vice versa. In conclusion, our study reveals c-FLIP/SMAD2/3 signaling pathway as a novel mechanism of antitumor activity of thiostrepton.

Keywords:

• Thiostrepton
• c-FLIP
• SMAD2/3
• triple-negative breast cancer (TNBC)

Disclosure statement

No potential conflict or interest was reported by the author(s).

Additional information

Funding

This work was financially supported by CAMS Innovation Fund for Medical Sciences [CIFMS, 2022-I2M-1-016, 2021-I2M-1-030]; the National Natural Science Foundation of China [81702934]; Beijing Natural Science Foundation [7202132].