Cephalochromin induces G0/G1 cell cycle arrest and apoptosis in A549 human non-small-cell lung cancer cells by inflicting mitochondrial disruption

Che Jen Hsiao, George Hsiao, Wei Lin Chen, Shih Wei Wang, Chun Ping Chiang, Li Ya Liu, Jih Hwa Guh, Zong-Huei Li, Chi Li Chung

Research output: Contribution to journalArticle

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Abstract

The fungus-derived compound cephalochromin, isolated from the fermented broth of Cosmospora vilior YMJ89051501, shows growth-inhibitory and apoptotic activity against human lung cancer A549 cells in a concentration-dependent manner with an IC50 value of 2.8 μM at 48 h. Cephalochromin induced cell cycle arrest at the G0/G1 phase through down-regulation of cyclin D1, cyclin E, Cdk 2, and Cdk 4 expressions. Cephalochromin markedly increased the hypodiploid sub-G1 phase (apoptosis) of the cell cycle at 48 h as measured by flow cytometric analysis. Reactive oxygen species generation and loss of the mitochondrial membrane potential (MMP) were also markedly induced by cephalochromin. Moreover, the immunoblotting assays showed that cephalochromin reduced survivin and Bcl-xL expression and induced the activation of caspase-8, -9, and -3 and the cleavage of poly(ADP-ribose) polymerase, indicating the involvement of a caspase signaling cascade. The caspase inhibitor Z-VAD-fmk significantly suppressed cephalochromin-induced apoptosis. Cephalochromin also triggered LC3 II, autophagic marker, expression. Taken together, this is the first report that cephalochromin induced an antiproliferative effect on human lung cancer cells through mitochondrial disruption and down-regulation of survivin, leading to cell cycle arrest at the G0/G1 phase, loss of MMP, and subsequently apoptotic cell death.

Original languageEnglish
Pages (from-to)758-765
Number of pages8
JournalJournal of Natural Products
Volume77
Issue number4
DOIs
Publication statusPublished - Apr 25 2014

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G1 Phase Cell Cycle Checkpoints
Non-Small Cell Lung Carcinoma
Cells
Apoptosis
G1 Phase
Cell Cycle Resting Phase
Mitochondrial Membrane Potential
Cell Cycle Checkpoints
Lung Neoplasms
Down-Regulation
Membranes
Cyclin E
Caspase Inhibitors
Poly(ADP-ribose) Polymerases
cephalochromin
Caspase 9
Caspase 8
Cyclin D1
Cell death
Caspases

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Pharmaceutical Science
  • Analytical Chemistry
  • Organic Chemistry
  • Molecular Medicine
  • Complementary and alternative medicine

Cite this

Cephalochromin induces G0/G1 cell cycle arrest and apoptosis in A549 human non-small-cell lung cancer cells by inflicting mitochondrial disruption. / Hsiao, Che Jen; Hsiao, George; Chen, Wei Lin; Wang, Shih Wei; Chiang, Chun Ping; Liu, Li Ya; Guh, Jih Hwa; Li, Zong-Huei; Chung, Chi Li.

In: Journal of Natural Products, Vol. 77, No. 4, 25.04.2014, p. 758-765.

Research output: Contribution to journalArticle

Hsiao, Che Jen ; Hsiao, George ; Chen, Wei Lin ; Wang, Shih Wei ; Chiang, Chun Ping ; Liu, Li Ya ; Guh, Jih Hwa ; Li, Zong-Huei ; Chung, Chi Li. / Cephalochromin induces G0/G1 cell cycle arrest and apoptosis in A549 human non-small-cell lung cancer cells by inflicting mitochondrial disruption. In: Journal of Natural Products. 2014 ; Vol. 77, No. 4. pp. 758-765.
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