期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/ijms22094870
关键词
betulinic acid; melanoma; mitochondria; OXPHOS; glycolysis; apoptotic markers; mitochondrial membrane potential
资金
- Romanian Ministry of Research and Innovation, CNCS-UEFISCDI, within PNCDI III [PN-III-P1-1.1-PD-2016-1982]
- Romanian Ministry of Education and Research, CNCS-UEFISCDI, within PNCDI III, acronym BAPRONIO [PN-III-P1-1.1-TE2019-2134]
The study indicates that betulinic acid has significant effects on mitochondrial bioenergetics and cellular behavior in melanoma cells, inducing mitochondrial dysfunction and apoptotic cell death, making it a potential strategy for treating melanoma.
Melanoma represents one of the most aggressive and drug resistant skin cancers with poor prognosis in its advanced stages. Despite the increasing number of targeted therapies, novel approaches are needed to counteract both therapeutic resistance and the side effects of classic therapy. Betulinic acid (BA) is a bioactive phytocompound that has been reported to induce apoptosis in several types of cancers including melanomas; however, its effects on mitochondrial bioenergetics are less investigated. The present study performed in A375 human melanoma cells was aimed to characterize the effects of BA on mitochondrial bioenergetics and cellular behavior. BA demonstrated a dose-dependent inhibitory effect in both mitochondrial respiration and glycolysis in A375 melanoma cells and at sub-toxic concentrations (10 mu M) induced mitochondrial dysfunction by eliciting a decrease in the mitochondrial membrane potential and changes in mitochondria morphology and localization. In addition, BA triggered a dose-dependent cytotoxic effect characterized by apoptotic features: morphological alterations (nuclear fragmentation, apoptotic bodies) and the upregulation of pro-apoptotic markers mRNA expression (Bax, Bad and Bak). BA represents a viable therapeutic option via a complex modulatory effect on mitochondrial metabolism that might be useful in advanced melanoma or as reliable strategy to counteract resistance to standard therapy.
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