Morusinol Exhibits Selective and Potent Antitumor Activity Against Human Liver Carcinoma by Inducing Autophagy, G2/M Cell Cycle Arrest, Inhibition of Cell Invasion and Migration, and Targeting of Ras/MEK/ERK Pathway
Zhen Zhu, Tianyu Xiao, Xuejiao Chang, Yanfei Hua, Jinli Gao
Department of Pathology, Shanghai East Hospital, Shanghai, China (mainland)
Med Sci Monit 2019; 25:1864-1870
Liver cancer is one of the most commonly diagnosed cancers across the globe. The treatment is often difficult as it is diagnosed mostly at advanced stages. Moreover, the lack efficacious and less toxic drugs are another problem in the treatment of liver cancer. Against this background, in this study we evaluated the anticancer activity of morusinol against SK-HEP-1 liver cancer cells.
MATERIAL AND METHODS: The proliferation rate of liver cancer cell line was investigated by MTT assay. Autophagy was detected by transmission electron microscopy and cell cycle analysis was performed by flow cytometry. The protein expression was examined by Western blotting.
RESULTS: Morusinol inhibited the proliferation of liver cancer SK-HEP-1 cells, with an IC₅₀ of 20 µM against the SK-HEP-1liver cancer cells. Further investigations indicated that the antiproliferative effects of morusinol are due to initiation of autophagy and G2/M cell cycle arrest, which was also associated with altered expression of several important proteins. Morusinol also suppressed the migration and invasion of SK-HEP-1liver cancer cells, and it suppressed the expression of p-MEK and p-ERK, leading to suppression of the Raf/MEK/ERK signalling cascade.
CONCLUSIONS: We found that morusinol exerts significant anticancer and autophagic effects on liver cancer cells and our results suggest the potential of morusinol in treatment of liver cancer.
Keywords: Apoptosis, Carcinoma, Hepatocellular, Cell Cycle, Flow Cytometry