Ursolic Acid Exhibits Potent Anticancer Effects in Human Metastatic Melanoma Cancer Cells (SK-MEL-24) via Apoptosis Induction, Inhibition of Cell Migration and Invasion, Cell Cycle Arrest, and Inhibition of Mitogen-Activated Protein Kinase (MAPK)/ERK Signaling Pathway
Authors: Pengcheng Liu
Ruili Du
Xin Yu
Journal: Medical Science Monitor (2019)
Discipline: CLINICAL MEDICINE
Keywords: Ursolic acid; anticancer potential; metastatic melanoma cells; cell viability; apoptosis
Affiliations: Department of Hand and Pediatric Surgery, The First Hospital of Jilin University, Changchun, Jilin, China (mainland)., Jilin Province Key Laboratory of Tissue Repair, Reconstruction and Regeneration, Changchun, Jilin, China (mainland)., Department of Clinical Laboratory Medicine, The Second Hospital of Changchun City, Changchun, Jilin, China (mainland).

Abstract:  BACKGROUND Ursolic acid is an important bioactive triterpenoid that has been reported to be of tremendous pharmacological importance. However, the anticancer potential of ursolic acid has not been examined against metastatic melanoma cells. Therefore, in this study we examined the anticancer potential of ursolic acid and its mode of action. MATERIAL AND METHODS WST-1 and colony formation assays were used for cell viability assessment. Cell cycle analysis was performed by flow cytometry. Apoptosis was detected by AO/EB staining using fluorescence microscopy. Cell migration and invasion were assessed by Boyden chamber assay. Protein expression was checked by Western blotting. RESULTS The results revealed that ursolic acid exerts significant (p&lt;0.01) growth-inhibitory effects on SK-MEL-24 cells. The IC₅₀ of ursolic acid against SK-MEL-24 cells was 25 µM. Our investigation of the underlying mechanism revealed that ursolic acid prompts apoptotic cell death of the SK-MEL-24 cells, which was linked with increased expression of Bax and Caspase 3 and 9, and decreased expression of Bcl-2. Ursolic acid also halted the SK-MEL-24 cells at G0/G1 phase of the cell cycle and also downregulated the expression of Cyclin B1 and Cdc25. Ursolic acid significantly (p&lt;0.01) inhibited the migration and invasion of SK-MEL-2 cells, indicative of its anti-metastatic potential. Finally, ursolic acid inhibited the MAPK/ERK pathway by suppressing the expression of p-P38 and p-ERK. CONCLUSIONS Ursolic acid appears to be a potent molecule for the treatment of melanoma. 

Retracted: Yes

PubPeer comments:
 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] From [Zhu et al (2019)] : 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] Different cell-lines, treatments and authors but same images. , 
 ![file] , 
 Fig 3.  Effect of ursolic acid on apoptosis induction in SK-Mel-24 cells. The results show that ursolic acid increases apoptotic cells in a concentration-dependent manner . ![file] In the 25 micro-M panel, three cells are surprisingly similar (after some rescaling). , 
 Fig 3 again *[right]*, rotated through 180 deg for convenience. *[left]* Fig 5 from [Wu et al (2020)] .  DAPI staining assay showing apoptotic cells after tormentic acid treatment (arrows). ![file] , 
 *[left]* Figure 8 from [Liu, Du Yu (2019)] .  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. *[right]* Figure 4 from [Han, Shi Li (2019)] .  Effects of beta-lapachone on the invasion of the HNE1 nasopharyngeal carcinoma cells as determined by Transwell assay. ![file] , 
 #1 Figs 7, 8 again: ![] More sightings! Fig 5D from [Si et al (2019)] .  Effect of miR-27a inhibition on ...(D) cell invasion of the SK-OV3 cells : ![] Figure 5 from [Jiang et al (2020)] .  Transwell assay showing cell invasion in miR-NC and miR-24 mimics transfected SNU-1 gastric cancer cells. ![file] , 
 Retracted [16 Jan 2021] .  Retraction of this publication has been requested by the authors due to problems with reproducibility. The problem being that the results reproduced other authors figures **too closely**. , 
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