Antitumor‑ and apoptosis‑inducing effects of pomolic acid against SK‑MEL‑2 human malignant melanoma cells are mediated via inhibition of cell migration and sub‑G1 cell cycle arrest Retraction in /10.3892/mmr.2021.12120

Li,Tian‑Hang; Yan,Hong‑Xia

doi:10.3892/mmr.2017.7977

Antitumor‑ and apoptosis‑inducing effects of pomolic acid against SK‑MEL‑2 human malignant melanoma cells are mediated via inhibition of cell migration and sub‑G1 cell cycle arrest

Retraction in: /10.3892/mmr.2021.12120

Authors:
- Tian‑Hang Li
- Hong‑Xia Yan
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Affiliations: Department of Dermatology, Jining First People's Hospital, Jining, Shandong 272000, P.R. China
Published online on: November 6, 2017 https://doi.org/10.3892/mmr.2017.7977
Pages: 1035-1040

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Abstract

Malignant melanoma is the leading cause of mortality among the skin‑associated diseases because of its highly metastatic nature and lethality. The aim of the present study was to evaluate antitumor and apoptosis effects of pomolic acid, a pentacyclic triterpene, against SK‑MEL‑2 human malignant melanoma cells. Its effect on cell migration and cell cycle arrest were also studied. An MTT assay was used to assess the cell cytotoxicity effects induced by pomolic acid. Fluorescence microscopy using acridine orange/propidium iodide and Hoechst 33342 staining, along with transmission electron microscopy (TEM), was used to study the effects of pomolic acid on apoptosis induction in these cells. The effects of pomolic acid on cell migration were studied using an in vitro wound healing assay. The effects of pomolic acid on cell cycle phase distribution were evaluated by flow cytometry using propidium iodide as fluorescent probe. The results revealed that pomolic acid induced significant dose‑ and time‑dependent antiproliferative effects in SK‑MEL‑2 human malignant melanoma cells, with IC50 values of 110.3, 88.1 and 79.3 µM after 24, 48 and 72 h, respectively. Pomolic acid‑treated cells exhibited red fluorescence, and the intensity of this fluorescence increased in a dose‑dependent manner, indicating apoptosis induction. After the cells were treated with 25, 75 and 150 µM pomolic acid, significant morphological alterations characteristic of apoptosis were observed by TEM, including loss of microvilli, a damaged plasma membrane, damaged cellular organelles and enlarged lysosomes. Pomolic acid also led to sub‑G1 cell cycle arrest, and inhibited cancer cell migration in a dose‑dependent manner. These results implicate pomolic acid as a potential therapeutic agent for the treatment of malignant melanoma.

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1	Garbe C: Epidemiology of skin cancerGarbe C, Dummer R, Kaufmann R and Tilgen W: Dermatologic Oncology [in German]. Berlin, Heidelberg, New York, Tokyo: Springer; pp. 40–56. 1997
2	Rager EL, Bridgeford EP and Ollila DW: Cutaneous melanoma: Update on prevention, screening, diagnosis, and treatment. Am Fam Physician. 72:269–276. 2005.PubMed/NCBI
3	Maddodi N and Setaluri V: Role of UV in cutaneous melanoma. Photochem Photobiol. 84:528–536. 2008. View Article : Google Scholar : PubMed/NCBI
4	Strouse JJ, Fears TR, Tucker MA and Wayne AS: Pediatric melanoma: Risk factor and survival analysis of the surveillance, epidemiology and end results database. J Clin Oncol. 23:4735–4741. 2005. View Article : Google Scholar : PubMed/NCBI
5	Lee C, Collichio F, Ollila D and Moschos S: Historical review of melanoma treatment and outcomes. Clin Dermatol. 31:141–147. 2013. View Article : Google Scholar : PubMed/NCBI
6	Sharma SD and Katiyar SK: Dietary grape seed proanthocyanidins inhibit UVB-induced cyclooxygenase-2 expression and other inflammatory mediators in UVB-exposed skin and skin tumors of SKH-1 hairless mice. Pharm Res. 27:1092–1102. 2010. View Article : Google Scholar : PubMed/NCBI
7	Moan J, Baturaite Z, Porojnicu AC, Dahlback A and Juzeniene A: UVA, UVB and incidence of cutaneous malignant melanoma in Norway and Sweden. Photochem Photobiol Sci. 11:191–198. 2012. View Article : Google Scholar : PubMed/NCBI
8	Demierre MF, Higgins PD, Gruber SB, Hawk E and Lippman SM: Statins and cancer prevention. Nat Rev Cancer. 5:930–942. 2005. View Article : Google Scholar : PubMed/NCBI
9	Chen LX, He YJ, Zhao SZ, Wu JG, Wang JT, Zhu LM, Lin TT, Sun BC and Li XR: Inhibition of tumor growth and vasculogenic mimicry by curcumin through down-regulation of the EphA2/PI3K/MMP pathway in a murine choroidal melanoma model. Cancer Biol Ther. 11:229–235. 2011. View Article : Google Scholar : PubMed/NCBI
10	Aziz MH, Reagan-Shaw S, Wu J, Longley BJ and Ahmad N: Chemoprevention of skin cancer by grape constituent resveratrol: Relevance to human disease? FASEB J. 19:1193–1195. 2005.PubMed/NCBI
11	Barthelman M, Bair WB III, Stickland KK, Chen W, Timmermann BN, Valcic S, Dong Z and Bowden GT: (−)-Epigallocatechin-3-gallate inhibition of ultraviolet B-induced AP-1 activity. Carcinogenesis. 19:2201–2204. 1998. View Article : Google Scholar : PubMed/NCBI
12	Li LH, Wu LJ, Zhou B, Wu Z, Tashiro S, Onodera S, Uchiumi F and Ikejima T: Silymarin prevents UV irradiation-induced A375-S2 cell apoptosis. Biol Pharm Bull. 27:1031–1036. 2004. View Article : Google Scholar : PubMed/NCBI
13	Nguyen N, Sharma A, Nguyen N, Sharma AK, Desai D, Huh SJ, Amin S, Meyers C and Robertson GP: Melanoma chemoprevention in skin reconstructs and mouse xenografts using isoselenocyanate-4. Cancer Prev Res (Phila). 4:248–258. 2011. View Article : Google Scholar : PubMed/NCBI
14	Bard S and Kirsner RS: Do nonsteroidal anti-inflammatory drugs prevent melanoma? J Invest Dermatol. 131:13942011. View Article : Google Scholar : PubMed/NCBI
15	Guruvayoorappan C and Kuttan G: Beta-carotene inhibits tumor-specific angiogenesis by altering the cytokine profile and inhibits the nuclear translocation of transcription factors in B16F-10 melanoma cells. Integr Cancer Ther. 6:258–270. 2007. View Article : Google Scholar : PubMed/NCBI
16	Wilson KS: Clinical activity of celecoxib in metastatic malignant melanoma. Cancer Invest. 24:740–746. 2006. View Article : Google Scholar : PubMed/NCBI
17	Yoo KH, Park JH, Lee DK, Fu YY, Baek NI and Chung IS: Pomolic acid induces apoptosis in SK-OV-3 human ovarian adenocarcinoma cells through the mitochondrial-mediated intrinsic and death receptor-induced extrinsic pathways. Oncol Lett. 5:386–390. 2013.PubMed/NCBI
18	Kerr JF, Wyllie AH and Currie AR: Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 26:239–257. 1972. View Article : Google Scholar : PubMed/NCBI
19	Wyllie AH, Kerr JF and Currie AR: Cell death: The significance of apoptosis. Int Rev Cytol. 68:251–306. 1980. View Article : Google Scholar : PubMed/NCBI
20	Liu JJ, Zhang L, Lou JM and Wu CY: Chalcone derivative, chana 1 induces inhibition of cell proliferation and prevents metastasis of pancreatic carcinoma. Adv Biomed Pharma. 2:115–119. 2015. View Article : Google Scholar
21	Reddy BS, Wang CX, Samaha H, Lubet R, Steele VE, Kelloff GJ and Rao CV: Chemoprevention of colon carcinogenesis by dietary perillyl alcohol. Cancer Res. 57:420–425. 1997.PubMed/NCBI
22	Hirano T, Abe K, Gotoh M and Oka K: Citrus flavone tangeretin inhibits leukaemic HL-60 cell growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes. Br J Cancer. 72:1380–1388. 1995. View Article : Google Scholar : PubMed/NCBI
23	Jiang MC, Yang-Yen HF, Yen JJ and Lin JK: Curcumin induces apoptosis in immortalized NIH 3T3 and malignant cancer cell lines. Nutr Cancer. 26:111–120. 1996. View Article : Google Scholar : PubMed/NCBI