Calotropin from Asclepias curasavica induces cell cycle arrest and apoptosis in cisplatin-resistant lung cancer cells

Autor: Jun Xu, Huan Zhang, Qiu-Tong Tan, Shaohui Cai, Ren-Wang Jiang, Enpan Mo, Rong-Rong Zhang, Xiao-Xiong Wang, Fang-Lan Liu
Rok vydání: 2016
Předmět:
0301 basic medicine
Cell cycle checkpoint
MAP Kinase Kinase 4
Apoptosis
Biochemistry
0302 clinical medicine
Caspase
Cyclin
bcl-2-Associated X Protein
chemistry.chemical_classification
Membrane Potential
Mitochondrial
biology
Caspase 3
Caspase 9
Cyclin-Dependent Kinases
Cell biology
Mitochondria
G2 Phase Cell Cycle Checkpoints
Gene Expression Regulation
Neoplastic
Cardenolides
Proto-Oncogene Proteins c-bcl-2
030220 oncology & carcinogenesis
Poly(ADP-ribose) Polymerases
Signal Transduction
Cyclin-Dependent Kinase Inhibitor p21
Poly ADP ribose polymerase
Biophysics
03 medical and health sciences
CDC2 Protein Kinase
Humans
Molecular Biology
Asclepias
Reactive oxygen species
Cyclin-dependent kinase 1
Plant Extracts
Cyclin-dependent kinase 2
Cyclin-Dependent Kinase 2
Cell Biology
Antineoplastic Agents
Phytogenic
030104 developmental biology
chemistry
A549 Cells
Drug Resistance
Neoplasm
Proteolysis
biology.protein
Cancer research
Cisplatin
Tumor Suppressor Protein p53
Reactive Oxygen Species
Zdroj: Biochemical and biophysical research communications. 478(2)
ISSN: 1090-2104
Popis: Calotropin (M11), an active compound isolated from Asclepias curasavica L., was found to exert strong inhibitory and pro-apoptotic activity specifically against cisplatin-induced resistant non-small cell lung cancer (NSCLC) cells (A549/CDDP). Molecular mechanism study revealed that M11 induced cell cycle arrest at the G2/M phase through down-regulating cyclins, CDK1, CDK2 and up-regulating p53 and p21. Furthermore, M11 accelerated apoptosis through the mitochondrial apoptotic pathway which was accompanied by increase Bax/Bcl-2 ratio, decrease in mitochondrial membrane potential, increase in reactive oxygen species production, activations of caspases 3 and 9 as well as cleavage of poly ADP-ribose polymerase (PARP). The activation and phosphorylation of JNK was also found to be involved in M11-induced apoptosis, and SP610025 (specific JNK inhibitor) partially prevented apoptosis induced by M11. In contrast, all of the effects that M11 induce cell cycle arrest and apoptosis in A549/CDDP cells were not significant in A549 cells. Drugs with higher sensitivity against resistant tumor cells than the parent cells are rather rare. Results of this study supported the potential application of M11 on the non-small lung cancer (NSCLC) with cisplatin resistance.
Databáze: OpenAIRE
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