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
Authors: Xuejiao Chang
Yanfei Hua
Tianyu Xiao
Jinli Gao
Zhen Zhu
Journal: Medical Science Monitor (2019)
Discipline: CLINICAL MEDICINE
Keywords: Liver cancer; morusinol; anticancer activity; SK-HEP-1 cells; proliferation
Affiliations: Department of Pathology, Shanghai East Hospital, Shanghai, China (mainland).

Abstract:  BACKGROUND 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. 

Retracted: Yes

PubPeer comments:
 Figure 6.  Inhibition of cell migration of SK-HEP-1 cells treated with morusinol at IC50. Figure 7.  Inhibition of cell invasion of SK-HEP-1 cells treated with morusinol at IC50. ![file] From [Liu, Du Yu (2019)] : Figure 7.  Effect of ursolic acid on the migration of SK-Mel-24 cells as shown by Western blotting. The results show that ursolic acid inhibits cell migration in a concentration-dependent manner. Figure 8.  Effect of ursolic acid on the invasion of the SK-Mel-24 cells. The results show that ursolic acid inhibits cell invasion in a concentration-dependent manner. ![file] Different cell-lines, treatments and authors but same images. , 
 Figure 3.  Induction of autophagy in SK-HEP-1 liver cancer cells as indicated by transmission electron microscopy at (A) 0 u00b5M, (B) 10 u00b5M, (C) 20 u00b5M, and (D) 40 u00b5M concentrations of morusinol. The autophagic vesicles increase with increase in the concentration of morusinol. The two highest-concentration panels seem to be enlargements of the 10-u00b5M panel. ![file] The same panels appear in Figure 2 of [Zhang et al (2019)] .  Electron microscopy images of Trifolirhizin treated SNU-5 cells showing induction of autophagy (arrows show autophagosomes). ![] Different cell-lines, different treatments, same images. , 
 Fig 8.  Concentration-dependent effect of morusinol on the Ras MEK ERK signalling pathway as determined by Western blot analysis . ![file] The number of lanes is not consistent. , 
 *[left]* Figure 4.  Effect of different concentrations of morusinol on the protein expression of autophagy-related proteins as determined by Western blotting. The experiments were repeated 3 times. The expression of L3II and Beclin I was increased, while that of p62 was decreased at IC50. *[right]* Fig 5 from [Zhang, Li Ji (2018)] .  Effect of Salviolone on the expression of the autophagy-related proteins. ![file] Different cell-lines, treatments and authors. Shared band. , 
 #1 Figs 6, 7 again: ![] Another sighting! Fig 5D from [Si et al (2019)] .  Effect of miR-27a inhibition on ...(D) cell invasion of the SK-OV3 cells : ![] , 
 #4 Another sighting of the wandering band! At left, Figure 5 from [Zhang et al (2018)] .  Effect of marrubenol at IC50 expression of autophagy-associated proteins as determined by western blot analysis. The figure indicates that marrubenol alters the expression of autophagy-related proteins, especially LC3-II . ![] , 
 Retracted [25 March 2021] .  An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures. ,