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伏利诺酸诱导黑色素瘤细胞程序性死亡的分子机制。

The molecular mechanisms of vulpinic acid induced programmed cell death in melanoma.

机构信息

Biotechnology Institute, Ankara University, Keçiören, Ankara, Turkey.

Department of Medical Biology, Faculty of Medicine, Sakarya University, Sakarya, Turkey.

出版信息

Mol Biol Rep. 2022 Sep;49(9):8273-8280. doi: 10.1007/s11033-022-07619-3. Epub 2022 Aug 12.

DOI:10.1007/s11033-022-07619-3
PMID:35960408
Abstract

BACKGROUNDS

Malignant melanoma is an aggressive skin tumor with a rapidly increasing incidence and there is not yet a successful treatment strategy. Vulpinic acid (VA) is derived from secondary metabolites from lichen species. In the current study, we, for the first time, investigated the anti-cancer effects of VA and the underlying mechanism VA induced programmed cell death in melanoma.

METHODS

The anti-cancer effects of VA on melanoma cells were evaluated by the xCELLigence system, flow cytometry, caspase-3 activity and RT-PCR analysis.

RESULTS

Our results showed that VA had a strong anti-proliferative effect on A-375 melanoma cells without damaging human epidermal melanocyte cells. Additionally, VA promoted apoptotic cell death through G2/M arrest and the activation of both intrinsic and extrinsic apoptosis pathways according to the analysis of 88 genes associated with apoptosis by qRT-PCR.

CONCLUSIONS

Our findings suggest that VA could become an alternative topical and transdermal treatment strategy in the treatment of maligned melanoma cancer. However, further investigations are needed to assess the underlying molecular mechanism of VA mediated apoptotic cell death in the treatment of melanoma.

摘要

背景

恶性黑色素瘤是一种侵袭性皮肤肿瘤,其发病率正在迅速上升,但目前尚无成功的治疗策略。熊果酸(VA)是从地衣物种的次生代谢物中提取的。在本研究中,我们首次研究了 VA 的抗癌作用及其诱导黑色素瘤细胞程序性死亡的潜在机制。

方法

通过 xCELLigence 系统、流式细胞术、caspase-3 活性和 RT-PCR 分析评估 VA 对黑素瘤细胞的抗癌作用。

结果

我们的结果表明,VA 对 A-375 黑色素瘤细胞具有很强的抗增殖作用,而对人表皮黑素细胞没有损伤。此外,根据 qRT-PCR 分析与细胞凋亡相关的 88 个基因,VA 通过 G2/M 期阻滞和内在和外在凋亡途径的激活促进细胞凋亡。

结论

我们的研究结果表明,VA 可能成为治疗恶性黑色素瘤的一种替代局部和经皮治疗策略。然而,仍需要进一步研究来评估 VA 介导的凋亡细胞死亡在治疗黑色素瘤中的潜在分子机制。

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本文引用的文献

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Mol Biol Rep. 2021 Aug;48(8):6025-6034. doi: 10.1007/s11033-021-06605-5. Epub 2021 Jul 30.
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Treatment of Advanced Melanoma in 2020 and Beyond.2020 年及以后的晚期黑色素瘤治疗。
J Invest Dermatol. 2021 Jan;141(1):23-31. doi: 10.1016/j.jid.2020.03.943. Epub 2020 Apr 5.
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Melanoma.黑素瘤。
地衣的药理作用:过去十年发生了什么?
Eurasian J Med. 2022 Dec;54(Suppl1):195-208. doi: 10.5152/eurasianjmed.2022.22335.
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The Role of Melanin in Skin Cancer.黑色素在皮肤癌中的作用。
Crit Rev Eukaryot Gene Expr. 2019;29(1):17-24. doi: 10.1615/CritRevEukaryotGeneExpr.2018024980.
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Melanoma Cell Death Mechanisms.黑色素瘤细胞死亡机制
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Determination of Vulpinic Acid Effect on Apoptosis and mRNA Expression Levels in Breast Cancer Cell Lines.狐衣酸对乳腺癌细胞系凋亡及mRNA表达水平的影响测定
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