Antiproliferative Activity of Selected Triterpene Acids from Rosemary on Metastatic Melanoma Cell Line WM-266-4

Authors

  • Suzana Isaković-Vidović Department of Radiology, Izola General Hospital, Izola, Slovenia; Faculty of Chemistry and Chemical Engineering, University of Maribor, Maribor, Slovenia https://orcid.org/0000-0001-7514-0137
  • Barbara Dariš Department of Pharmacology and Toxicology, Faculty of Medicine, Institute of Biomedical Sciences, University of Maribor, Maribor, Slovenia
  • Željko Knez Faculty of Chemistry and Chemical Engineering, University of Maribor, Maribor, Slovenia
  • Kristina Vidović Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Dejan Oprić Faculty of Medicine, Institute of Pathology, University of Belgrade, Belgrade, Serbia
  • Polonca Ferk Institute of Biostatistics and Medical Informatics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

DOI:

https://doi.org/10.3889/oamjms.2021.6176

Keywords:

Melanoma, Antiproliferative activity, Betulinic acid, Ursolic acid, Oleanolic acid

Abstract

BACKGROUND: Natural products and their derivatives, particularly secondary metabolites, have been recognized for many years as an important source of therapeutic agents. In this context, pentacyclic triterpene acids including betulinic acid (BA), oleanolic acid (OA), and ursolic acid (UA) are highly valuable triterpenic acids because of their wide range of biological activities.

AIM: Therefore, the aim of our study was to investigate any potential effect of BA, UA, and OA on human melanoma WM-266-4 cells’ proliferation activity.

METHODS: BA, UA, and OA have been prepared in dimethyl sulfoxide in concentration range from 0.002 to 200 μM separately or in selected combination (UA+OA ratio 1:1 or 3.5:1), while cells in cell culture medium served as controls. The rapid colorimetric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was used to measure proliferation activity of the metastatic melanoma cell line WM-266-4 after being exposed to selected concentrations of BA, UA, OA, or UA+OA and during different time periods. Student’s t-test was used for single statistical comparisons. Data were analyzed using IBM SPSS 25.0 (IBM Corp., Armonk, NY). To account for multiple comparisons bias, p < 0.001 was considered statistically significant.

RESULTS: Our results showed decreased cell proliferation activity after 4 h of incubation of WM-266-4 cells with BA, UA, OA, and UA+OA. The highest inhibitory effect was noted when cells were incubated with selected triterpenic acids and both combinations of UA+OA during the incubation period of 48 h. When compared to control cells, concentration of 2 μM was the lowest concentration of BA that showed a significant decrease of the cells’ proliferation activity regardless the incubation period (4 h, 24 h, and 48 h) (p < 0.001).

CONCLUSION: Our encouraging results could be a good starting point for further studies on possible use of BA, UA, and OA in prevention and treatment of metastatic melanoma.

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References

Carr S, Smith C, Wernberg J. Epidemiology and risk factors of melanoma. Surg Clin N Am. 2019;100(1):1-12. PMid:31753105 DOI: https://doi.org/10.1016/j.suc.2019.09.005

DeVita H, Rosenberg SA. Cancer: Principles and Practice of Oncology. 10th ed. New York: Lippincott Williams and Wilki; 2018.

Tripp MK, Watson M, Balk SJ, Swetter SM, Gershenwald E. State of the science on prevention and screening to reduce melanoma incidence and mortality: The time is now. CA Cancer J Clin. 2016;66(6):460-80. https://doi.org/10.3322/caac.21352 PMid:27232110 DOI: https://doi.org/10.3322/caac.21352

Forsea AM. Melanoma epidemiology and early detection in Europe: Diversity and disparities. Dermatol Pract Concept. 2020;10(3):e2020033. https://doi.org/10.5826/dpc.1003a33 PMid:32642304 DOI: https://doi.org/10.5826/dpc.1003a33

Padma VV. An overview of targeted cancer therapy. Biomedicine. 2015;5(4):19. PMid:26613930 DOI: https://doi.org/10.7603/s40681-015-0019-4

Wink M, Schimmer O. Molecular modes of action of defensive secondary metabolites. Ann Plant Rev Online. 2018;39:418. https://doi.org/10.1002/9781119312994.apr0418 DOI: https://doi.org/10.1002/9781119312994.apr0418

Abu-Darwish M, Efferth T. Medicinal plants from near east for cancer therapy. Front Pharmacol. 2018;9:56. https://doi.org/10.3389/fphar.2018.00056 PMid:29445343 DOI: https://doi.org/10.3389/fphar.2018.00056

Andrade JM, Faustino C, Garcia C, Ladeiras D, Reis CP, Rijo P. Rosmarinus officinalis L.: An update review of its phytochemistry and biological activity. Future Sci. 2018;2018:FSO283. https://doi.org/10.4155/fsoa-2017-0124 PMid:29682318 DOI: https://doi.org/10.4155/fsoa-2017-0124

Kashyap D, Tuli HS, Garg VK, Bhatnagar S, Sharma AK. Ursolic acid and quercetin. Promising anticancer phytochemicals with antimetastatic and antiangiogenic potential. Tumor Microenviron. 2018;1:9-15. https://doi.org/10.4103/tme.tme_3_17 DOI: https://doi.org/10.4103/tme.tme_3_17

Liu B, Ezeogu L, Zellmer L, Baofa Y, Ningzhi X, Dezhong JL. Protecting the normal in order to better kill the cancer. Cancer Med. 2015;4(9):1394-403. https://doi.org/10.1002/cam4.488 PMid:26177855 DOI: https://doi.org/10.1002/cam4.488

Baishya R, Nayak DK, Kumar D, Sinha S, Gupta A, Ganguly S, et al. Ursolic acid loaded PLGA nanoparticles: In vitro and in vivo evaluation to explore tumor targeting ability on B16F10 melanoma cell lines. Pharm Res. 2016;33:2691-703. https://doi.org/10.1007/s11095-016-1994-1 PMid:27431865 DOI: https://doi.org/10.1007/s11095-016-1994-1

Momtaz S, Niaz K, Maqbool F, Abdollahi M, Rastrelli L, Nabavi SM. STAT3 targeting by polyphenols: Novel therapeutic strategy for melanoma. Biofactors. 2017;43(3):347-70. https://doi.org/10.1002/biof.1345 PMid:27896891 DOI: https://doi.org/10.1002/biof.1345

Kim GJ, Jo HJ, Lee KJ, Choi JW, An JH. Oleanolic acid induces p53-dependent apoptosis via the ERK/JNK/AKT pathway in cancer cell lines in prostatic cancer xenografts in mice. Oncotarget. 2018;29(9):26370-86. https://doi.org/10.18632/oncotarget.25316 PMid:29899865 DOI: https://doi.org/10.18632/oncotarget.25316

Dinku W, Isaksson J, Rylandsholm FG, Bouř P, Brichtová E, Un Choi S, et al. Anti-proliferative activity of a novel tricyclic triterpenoid acid from Commiphora africana resin against four human cancer cell lines. Appl Biol Chem. 2020;63:16. https://doi.org/10.1186/s13765-020-00499-w DOI: https://doi.org/10.1186/s13765-020-00499-w

Lamponi S, Baratto MC, Miraldi E, Baini G, Biagi M. Chemical profile, antioxidant, anti-proliferative, anticoagulant and mutagenic effects of a hydroalcoholic extract of Tuscan Rosmarinus officinalis. Plants. 2021;10(1):97. https://doi.org/10.3390/plants10010097 PMid:33418860 DOI: https://doi.org/10.3390/plants10010097

Chudzik M, Korzonek-Szlacheta I, Król W. Triterpenes as potentially cytotoxic compounds. Molecules. 2015;20:1610-25. https://doi.org/10.3390/molecules20011610 PMid:25608043 DOI: https://doi.org/10.3390/molecules20011610

Bildziukevich U, Özdemir Z, Wimmer Z. Recent achievements in medicinal and supramolecular chemistry of betulinic acid and its derivatives. Molecules. 2019;24(19):3546. https://doi.org/10.3390/molecules24193546 PMid:31574991 DOI: https://doi.org/10.3390/molecules24193546

Oprean C, Ivan A, Bojin F, Cristea M, Soica C, Draghia L, et al. Selective in vitro anti-melanoma activity of ursolic and oleanolic acids. Toxicol Mech Methods. 2018;28(2):148-56. https://doi.org/10.1080/15376516.2017.1373881 PMid:28868958 DOI: https://doi.org/10.1080/15376516.2017.1373881

Shao J, Fang Y, Zhao R, Chen F, Yang M, Jiang J, et al. Evolution from small molecule to nano-drug delivery systems: An emerging approach for cancer therapy of ursolic acid. Asian J Pharm Sci. 2020;15(6):685-700. https://doi.org/10.1016/j.ajps.2020.03.001 PMid:33363625 DOI: https://doi.org/10.1016/j.ajps.2020.03.001

López-Hortas L, Pérez-Larrán P, Gonzáles-Muňoz MJ, Falque E, Domínguez H. Recent developments on the extraction and application of ursolic acid. Food Res Int. 2018;103:130-49. https://doi.org/10.1016/j.foodres.2017.10.028 PMid:29389599 DOI: https://doi.org/10.1016/j.foodres.2017.10.028

Zhu YY, Huang HY, Wu YL. Anticancer and apoptotic activities of oleanolic acid are mediated through cell cycle arrest and disruption of mitochondrial membrane potential in HepG2 human hepatocellular carcinoma cells. Mol Med Rep. 2015;12(4):5012-8. https://doi.org/10.3892/mmr.2015.4033 PMid:26151733 DOI: https://doi.org/10.3892/mmr.2015.4033

Bai X, Lai T, Zhou T, Li Y, Li X, Zhang H. In vitro antioxidant activities of phenols and oleanolic acid from mango peel and their cytotoxic effect on a549 cell line. Molecules. 2018;23(6):1395. https://doi.org/10.3390/molecules23061395 PMid:29890672 DOI: https://doi.org/10.3390/molecules23061395

Gidwani B, Vyas A. A comprehensive review on cyclodextrinbased carriers for delivery of chemotherapeutic cytotoxic anticancer drugs. Biomed Res Int. 2015;2015:198268. https://doi.org/10.1155/2015/198268 PMid:26582104. DOI: https://doi.org/10.1155/2015/198268

Sun HX, Zhang JX, Ye YP, Pan Y, Shen Y. Cytotoxic pentacyclic triterpenoids from the rhizome of Astilbe chinensis. Helv Chim Acta. 2003;86(7):2414-23. https://doi.org/10.1002/hlca.200390194 PMid:15013190 DOI: https://doi.org/10.1002/hlca.200390194

Dash SK, Chattopadhyay S, Karmakar P, Roy S. Antileukemic activity of betulinic acid from bulk to self-assembled structure. BLDE Univ J Health Sci. 2016;1:14-9. https://doi.org/10.4103/2456-1975.183269 DOI: https://doi.org/10.4103/2456-1975.183269

Hordyjewska A, Ostapiuk A, Horecka A, Kurzepa J. Betulin and betulinic acid: triterpenoids derivatives with a powerful biological potential. Phytochem Rev. 2019;18:929-51. https://doi.org/10.1007/s11101-019-09623-1 DOI: https://doi.org/10.1007/s11101-019-09623-1

Yin R, Li T, Tian JX, Liu RH. Ursolic acid, a potential anticancer compound for breast cancer therapy. Crit Rev Food Sci Nutr. 2018;58(4):568-74. https://doi.org/10.1080/10408398.2016.1203755 PMid:27469428 DOI: https://doi.org/10.1080/10408398.2016.1203755

Gao Y, Yuan Y, Song G, Lin SQ. Inhibitory effect of ursolic acid and oleanolic acid from Eriobotrya fragrans on A549 cell viability in vivo. Genet Mol Res. 2016;15(2):239-42. https://doi.org/10.4238/gmr.15028642 PMid:27323036 DOI: https://doi.org/10.4238/gmr.15028642

Soica C, Oprean C, Borcan F, Danciu C, Trandafirescu C, Coricovac D, et al. The synergistic biologic activity of oleanolic and ursolic acids in complex with hydroxypropyl-γ-cyclodextrin. Molecules. 2014;19:4924-440. https://doi.org/10.3390/molecules19044924 PMid:247474649 DOI: https://doi.org/10.3390/molecules19044924

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Published

2021-06-13

How to Cite

1.
Isaković-Vidović S, Dariš B, Knez Željko, Vidović K, Oprić D, Ferk P. Antiproliferative Activity of Selected Triterpene Acids from Rosemary on Metastatic Melanoma Cell Line WM-266-4. Open Access Maced J Med Sci [Internet]. 2021 Jun. 13 [cited 2024 Mar. 28];9(B):515-21. Available from: https://oamjms.eu/index.php/mjms/article/view/6176