Hypocrellin A-based photodynamic action induces apoptosis in A549 cells through ROS-mediated mitochondrial signaling pathway.
10.1016/j.apsb.2018.12.004
- Author:
Shanshan QI
1
;
Lingyuan GUO
1
;
Shuzhen YAN
1
;
Robert J LEE
2
;
Shuqin YU
3
;
Shuanglin CHEN
1
Author Information
1. Jiangsu Province Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
2. College of Pharmacy, the Ohio State University, Columbus, OH 43210, USA.
3. Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
- Publication Type:Journal Article
- Keywords:
ACN, acetonitrile;
CLSM, confocal laser scanning confocal microscopy;
DCFH-DA, 2′,7′-dichlorofuorescin diacetate;
DMEM, Dulbecco׳s modified Eagle׳s medium;
Dox, doxorubicin;
ECL, enhanced chemiluminescence;
FCCP, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone;
FDR, false discovery rate;
GO, gene ontology;
HA, hypocrellin A;
HRP, horseradish peroxidase;
Hypocrellin A;
IAA, iodoacetamide;
IKK, IκB kinase complex;
JC-1, 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-benzimidazolcarbocyanine iodide;
LC–MS/MS;
MMP, mitochondrial membrane potential;
MPT, mitochondrial permeability transition;
NAC, N-acetyl-l-cysteine;
OCR, oxygen consumption rate;
PDT, photodynamic therapy;
PI, propidium iodide;
PS, photosensitizer;
Photodynamic therapy;
Proteomic;
ROS, reactive oxygen species;
Reactive oxygen species;
SCX, strong cation exchange;
TCM, traditional Chinese medicinal;
TEM, transmission electron microscope;
TFA, trifluoroacetic acid;
UA, urea;
iTRAQ;
iTRAQ, isobaric tag for relative and absolute quantitation;
z-IETD-fmk, z-Ile-Glu-Asp-fluoromethylketone;
z-LEHD-fmk, z-Leu-Glu(OMe)-His-Asp(OMe)-fluoromethylketone;
z-VAD-fmk, z-Val-Ala-Asp-fluoromethylketone
- From:
Acta Pharmaceutica Sinica B
2019;9(2):279-293
- CountryChina
- Language:English
-
Abstract:
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 , 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.
