Hypocrellin A-based photodynamic action induces apoptosis in A549 cells through ROS-mediated mitochondrial signaling pathway

Over recent decades, many studies have reported that hypocrellin A (HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in hum...

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Main Authors: Shanshan Qi (Author), Lingyuan Guo (Author), Shuzhen Yan (Author), Robert J. Lee (Author), Shuqin Yu (Author), Shuanglin Chen (Author)
Format: Book
Published: Elsevier, 2019-03-01T00:00:00Z.
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100 1 0 |a Shanshan Qi  |e author 
700 1 0 |a Lingyuan Guo  |e author 
700 1 0 |a Shuzhen Yan  |e author 
700 1 0 |a Robert J. Lee  |e author 
700 1 0 |a Shuqin Yu  |e author 
700 1 0 |a Shuanglin Chen  |e author 
245 0 0 |a Hypocrellin A-based photodynamic action induces apoptosis in A549 cells through ROS-mediated mitochondrial signaling pathway 
260 |b Elsevier,   |c 2019-03-01T00:00:00Z. 
500 |a 2211-3835 
500 |a 10.1016/j.apsb.2018.12.004 
520 |a Over recent decades, many studies have reported that hypocrellin A (HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy (PDT). A temporal quantitative proteomics approach by isobaric tag for relative and absolute quantitation (iTRAQ) 2D liquid chromatography with tandem mass spectrometric (LC-MS/MS) was introduced to help clarify molecular cytotoxic mechanisms and identify candidate targets of HA-induced apoptotic cell death. Specific caspase inhibitors were used to further elucidate the molecular pathway underlying apoptosis in PDT-treated A549 cells. Finally, down-stream apoptosis-related protein was evaluated. Apoptosis induced by HA was associated with cell shrinkage, externalization of cell membrane phosphatidylserine, DNA fragmentation, and mitochondrial disruption, which were preceded by increased intracellular reactive oxygen species (ROS) generations. Further studies showed that PDT treatment with 0.08 µmol/L HA resulted in mitochondrial disruption, pronounced release of cytochrome c, and activation of caspase-3, -9, and -7. Together, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation. KEY WORDS: Hypocrellin A, Photodynamic therapy, Reactive oxygen species, Proteomic, LC-MS/MS, iTRAQ 
546 |a EN 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Acta Pharmaceutica Sinica B, Vol 9, Iss 2, Pp 279-293 (2019) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S2211383518303186 
787 0 |n https://doaj.org/toc/2211-3835 
856 4 1 |u https://doaj.org/article/6fb65c84f29d4930baf2418d32264b4d  |z Connect to this object online.