Antiproliferative and apoptotic effects of caffeic acid on SK-Mel-28 human melanoma cancer cells
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Cutaneous melanoma (CM) is an extremely aggressive cancer presenting low survival and high mortality. The vast majority of patients affected by this disease does not respond or show resistance to the chemotherapeutic drugs, which makes the treatment ineffective. In this sense, the necessity for the development of new agents to assist in CM therapy is extremely important. One of the sources of great interest in this search are compounds of natural origin. Among these compounds, caffeic acid has demonstrated a broad spectrum of pharmacological activities as well as antitumor effects in some types of cancer. Therefore, the objective of this work was to investigate the possible antitumor effect of caffeic acid on the SK-Mel-28 cell line, human CM cells. Cells were cultured in flasks with culture medium containing fetal bovine serum, antibiotic, and antifungal, and maintained in ideal conditions. Cells were treated with 25 µM, 50 µM, 100 µM, 150 µM and 200 µM of caffeic acid and dacarbazine at 1 mg/mL. We verified the effect on cell viability and cell death, apoptosis, cell cycle, colony formation and gene expression of caspases. Results showed a decrease in cell viability, cell death induction by apoptosis, inhibition of colony formation, modulation of cell cycle and alterations in gene expression of caspases after caffeic acid treatment. These results suggest an antitumor effect of the compound on SK-Mel-28 cells. This study provides original information on mechanisms by which caffeic acid may play a key role in preventing tumor progression in human melanoma cells.
KeywordsMelanoma Natural compounds Cytotoxicity Apoptosis Cell cycle Gene expression
The authors would like to thank the financial support of CAPES [CAPES/PROEX—Process Numbers: 23038.005848/2018-31 and 88882.182142/2018-01] and CNPq [MDB Project. No. 449485/2014-5], Brazil. Funding sources are non-profit governmental agencies and had no role in study design, in the collection, analysis, and interpretation of the data, in the writing of the manuscript, and in the decision for publication.
Compliance with ethical standards
Conflict of interest
The authors declare that they no conflicts of interest.
All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Infromed consent was obtained from all individual participants in the study.
- 1.O’Sullivan J, O’Connor D (2018) The modern approach to targeting melanoma. In: Human skin cancers—pathways, mechanisms, targets and treatments. InTechOpen, LondonGoogle Scholar
- 5.Middleton MR, Grob JJ, Aaronson N, Fierlbeck G, Tilgen W, Seiter S, Gore M, Aamdal S, Cebon J, Coates A, Dreno B, Henz M, Schadendorf D, Kapp A, Weiss J, Fraass U, Statkevich P, Muller M, Thatcher N (2000) Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 18:158–166CrossRefPubMedGoogle Scholar
- 12.Assmann CE, Cadoná FC, Bonadiman BDSR, Dornelles EB, Trevisan G, Cruz IBMD (2018) Tea tree oil presents in vitro antitumor activity on breast cancer cells without cytotoxic effects on fibroblasts and on peripheral blood mononuclear cells. Biomed Pharmacother 103:1253–1261CrossRefPubMedGoogle Scholar
- 18.Kampa M, Alexaki V, Notas G, Nifli AP, Nistikaki A, Hatzoglou A, Bakogeorgou E, Kouimtzoglou E, Blekas G, Boskou D, Gravanis A, Castanas E (2004) Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action. Breast Cancer Res 6:R63–R74CrossRefPubMedGoogle Scholar
- 19.Takahashi H, Nguyen BCQ, Uto Y, Shahinozzaman M, Tawata S, Maruta H (2017) 1,2,3-Triazolyl esterization of PAK1-blocking propolis ingredients, artepillin C (ARC) and caffeic acid (CA), for boosting their anti-cancer/anti-PAK1 activities along with cell-permeability. Drug Discov Ther 11:104–109CrossRefPubMedGoogle Scholar
- 35.Kabała-Dzik A, Rzepecka-Stojko A, Kubina R, Jastrzębska-Stojko Ż, Stojko R, Wojtyczka RD, Stojko J (2017) Comparison of two components of propolis: caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) induce apoptosis and cell cycle arrest of breast cancer cells MDA-MB-231. Molecules 22:E1554CrossRefPubMedGoogle Scholar