Anthecotulide Sesquiterpene Lactone Exhibits Selective Anticancer Effects in Human Malignant Melanoma Cells by Activating Apoptotic and Autophagic Pathways, S-Phase Cell Cycle Arrest, Caspase Activation, and Inhibition of NF-κB Signalling Pathway
Authors: Xiuping Han
Chenyang Li
Journal: Medical Science Monitor (2019)
Discipline: CLINICAL MEDICINE
Keywords: anthecotulide; SK-MEL-24; malignant melanoma cells; apoptosis; autophagy
Affiliations: Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China (mainland)

Abstract:  BACKGROUND We examined the anticancer potential of anthecotulide against SK-MEL-24 malignant melanoma cells. The apoptotic and autophagic effects of anthecotulide were also investigated. MATERIAL AND METHODS The cell viability of SK-MEL-24 human malignant melanoma cells was evaluated by WST-1 assay. Fluorescence microscopy using acridine orange and ethidium bromide staining, as well as Western blot analysis, were used to study apoptotic effects induced by anthecotulide. Autophagy was assessed by Western blot analysis and fluorescence microscopy. Effects of anthecotulide on cell cycle progression were analyzed by flow cytometry. RESULTS The results revealed that anthecotulide exerts significant growth-inhibitory effects on SK-MEL-24 cells. The IC₅₀ of anthecotulide against the SK-MEL-24 cells was found to be 10 µM. However, the anticancer effects against the normal cells were minimal (IC50; 100 µM). Investigation of the underlying mechanism revealed that anthecotulide prompts apoptotic cell death of the SK-MEL-24 cells, which was linked with increased expression of Bax and decreased expression of Bcl-2. It also triggered concentration-dependent activation of caspase 3 and 9. Anthecotulide induced autophagy in the SK-MEL-24 cells, which was associated with upregulation of LC3 II and Beclin-1 expression. Anthecotulide also halted the SK-MEL-24 cells at S-phase of the cell cycle and downregulated the expression of Cyclin B1. However, the expression of p27 was upregulated. CONCLUSIONS These results indicate anthecotulide is a potent lead molecule for the treatment of melanoma. In vivo and other related experiments are warranted to further assess this promising drug candidate. 

Retracted: Yes

PubPeer comments:
 *[right]* Fig 8 from [Li Han (2019)] .  Figure 8. Effect of anthecotulide on NF-kB expression at indicated concentrations as depicted by Western blot analysis. *[left]* Fig 5 from [Ding et al (2019)] .  The effect of angustifoline on apoptosis-related proteins (Bcl-2 and Bax) in COLO-205 human colon cancer cells as depicted by western blotting . ![file] , 
 Figure 2.  AO EB staining showing the induction of apoptosis in SK-MEL-24 melanoma cells at indicated concentrations. The experiments were performed in triplicate. Green arrows depict normal cells, yellow arrows depict early apoptosis, and the red arrows depict late apoptosis . 10 u03bcM, 420u03bcM *[sic]*. Lower versions have lightness and contrast enhanced. ![file] The sharp edges to the red-tinged halos around the red cells create an impression that they were added by cut- -paste. Note also the sharp-edged areas of black background in the 10 u03bcM panel. , 
 Retracted [25 March 2021] .  Retracted, due to breach of publishing guidelines, following the identification of non-original and manipulated figure images. ,