期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 22, 页码 -出版社
MDPI
DOI: 10.3390/ijms232214149
关键词
dieckol; autophagy; apoptosis; cell death; melanoma; antitumor activity
资金
- Pukyong National University Research Abroad Fund [C-D-2019-0004]
Dieckol, a natural polyphenol, inhibits the growth of melanoma cells by inducing apoptotic cell death through affecting lysosomal function and mitochondrial membrane. This suggests its potential value as a chemotherapeutic drug candidate for melanoma treatment.
Dieckol is a natural brown algal-derived polyphenol and its cytotoxic potential against various types of cancer cells has been studied. However, the effects of dieckol on autophagy in cancer cells remain unknown. Here, we show that dieckol inhibits the growth of A375 human melanoma cells by inducing apoptotic cell death, which is associated with lysosomal dysfunction and the inhibition of autophagic flux. Dieckol induces autophagosome accumulation by inhibiting autophagosome-lysosome fusion. Moreover, dieckol not only triggers lysosomal membrane permeabilization, followed by an increase in lysosomal pH and the inactivation of cathepsin B and D, but also causes the loss of mitochondrial membrane potential. Importantly, a cathepsin D inhibitor partially relieved dieckol-induced mitochondrial membrane impairment and caspase-mediated apoptosis. Collectively, our findings indicate that dieckol is a novel autophagy inhibitor that induces apoptosismediated cell death via lysosomal dysfunction and mitochondrial membrane impairment in A375 human melanoma cells. This suggests the novel potential value of dieckol as a chemotherapeutic drug candidate for melanoma treatment.
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