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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.
Med Sci Monit 2019; 25:1283-1290MS

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<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<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.

Authors+Show 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).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).

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30772887

Citation

Liu, Pengcheng, et al. "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." Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, vol. 25, 2019, pp. 1283-1290.
Liu P, Du R, Yu X. 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. Med Sci Monit. 2019;25:1283-1290.
Liu, P., Du, R., & Yu, X. (2019). 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. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, 25, pp. 1283-1290. doi:10.12659/MSM.913069.
Liu P, Du R, Yu X. 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. Med Sci Monit. 2019 Feb 17;25:1283-1290. PubMed PMID: 30772887.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Liu,Pengcheng, AU - Du,Ruili, AU - Yu,Xin, Y1 - 2019/02/17/ PY - 2019/2/18/entrez PY - 2019/2/18/pubmed PY - 2019/5/11/medline SP - 1283 EP - 1290 JF - Medical science monitor : international medical journal of experimental and clinical research JO - Med. Sci. Monit. VL - 25 N2 - 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<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<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. SN - 1643-3750 UR - https://www.unboundmedicine.com/medline/citation/30772887/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_ L2 - https://www.medscimonit.com/download/index/idArt/913069 DB - PRIME DP - Unbound Medicine ER -