Activation of autophagy promotes the inhibitory effect of curcumin analog EF‐24 against MDA‐MB‐231 cancer cells

• Published in: Journal of biochemical and molecular toxicology 2024-02, Vol.38 (2), p.e23642-n/a
• Main Authors: Zhao, Yin‐Yin, Li, Jun, Wang, Hao‐Qi, Zheng, Hao‐Bo, Ma, Shi‐Wei, Zhou, Guang‐Zhou
• Format: Article
• Language: English
• Subjects: Anticancer properties; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antitumor activity; anti‐proliferation; Apoptosis; Autophagy; Breast cancer; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Proliferation; Curcumin; Curcumin - pharmacology; Curcumin - therapeutic use; curcumin analog; Female; Flow cytometry; Humans; MDA-MB-231 Cells; Rapamycin; reactive oxygen species; Reactive Oxygen Species - metabolism; Wound healing
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.23642

Breast cancer is the leading cause of cancer deaths in women worldwide. EF‐24, an analog of curcumin, has been shown to possess promising anticancer effects. However, the underlying mechanism remains elusive. In the present study, the inhibitory effect of EF‐24 against one breast cancer cell line, MDA‐MB‐231, and its anti‐migration ability were assessed by MTT, wound healing, and Transwell assay. Furthermore, we found that EF‐24 could induce initiation of autophagy as evidenced by fluorescence and electron microscope observation. EF‐24 also induced mitochondrial apoptosis in MDA‐MB‐231 cells as detected by Hoechst 33342 staining, flow cytometry analysis, and western blot analysis. In addition, the early autophagy inhibitor 3‐MA could reduce the cleavage of PARP protein and protect cells from EF‐24‐induced apoptosis, while the autophagy inducer (rapamycin) could enhance the anticancer effect of EF‐24 in MDA‐MB‐231 cells, which suggest that EF‐24 induces crosstalk between autophagy and apoptosis, which herein participate in the antiproliferative effect of EF‐24 in breast cancer cells. Moreover, removal of EF‐24‐activated ROS with NAC significantly reversed migration ability of MDA‐MB‐231 cells, indicating that EF‐24 exerted an inhibitory effect through a ROS‐mediating pathway. These results will help to elucidate the antitumor mechanism of curcumin analogs and to explore future potential clinical applications. EF‐24 induces crosstalk of autophagy and apoptosis, which participate in the antiproliferative effect of EF‐24 in MDA‐MB‐231 breast cancer cells.