Cycloartobiloxanthone Induces Human Lung Cancer Cell Apoptosis via Mitochondria-dependent Apoptotic Pathway.

Abstract

BACKGROUND:

Lung cancer is one of most malignant types of cancer and new anticancer agents are still required. Cycloartobiloxanthone, a flavonoid isolated from stem bark of Artocarpus gomezianus, has potential for being developed for anticancer therapy.

MATERIALS AND METHODS:

Cytotoxicity of cycloartobiloxanthone was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay against four human lung cancer cell lines (H23, H460, H292 and A549) and their half-maximal inhibitory concentrations (IC50) were assessed. Apoptotic induction in H460 cells was investigated by Hoechst 33342/propidium iodide (PI) staining assay and protein hallmarks of mitochondria-dependent apoptotic pathway were examined by western blot analysis.

RESULTS:

Cycloartobiloxanthone exhibited potent cytotoxic effect on both small and non-small cell lung cancer cells. Nuclear Hoechst/PI staining revealed that apoptotic cell death was the main mechanism of toxicity of cycloartobiloxanthone. The apoptosis-inducing potency of cycloartobiloxanthone was comparable to those of standard anticancer drugs cisplatin and etoposide at the same concentration. Protein analysis further showed that apoptosis was mediated via mitochondria-dependent pathway. p53 was activated in cells treated with cycloartobiloxanthone. Subsequently, pro-apoptotic protein B-cell lymphoma 2 (BCL2)-associated X protein (BAX) was found to be significantly increased, concomitantly with the decrease of anti-apoptotic proteins BCL2 and myeloid cell leukemia 1 (MCL1). Moreover, markers of the intrinsic apoptosis pathway, namely activated caspase-9, activated caspase-3, and cleaved poly(ADP-ribose)polymerase (PARP), dramatically increased in cycloartobiloxanthone-treated cells compared to the non-treated controls.

CONCLUSION:

Cycloartobiloxanthone has anticancer activity against human lung cancer cells by triggering mitochondrial apoptotic caspase-dependent mechanism. This compound might have promising effects for cancer therapy.

• Authors: Nattanan Losuwannarak, Boonchoo Sritularak, Pithi Chanvorachote
• Journal: In vivo (Athens, Greece) (In Vivo) 2018 Jan-Feb Vol. 32 Issue 1 Pg. 71-78 ISSN: 1791-7549 [Electronic] Greece
• PMID: 29275301 (Publication Type: Journal Article)
• Copyright: Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Antineoplastic Agents
• Apoptosis Regulatory Proteins
• Flavonoids
• cycloartobiloxanthone
• Caspases

Topics

• A549 Cells
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Artocarpus (chemistry)
• Blotting, Western
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Flavonoids (chemistry, pharmacology)
• Humans
• Lung Neoplasms (metabolism, pathology)
• Mitochondria (drug effects, metabolism)
• Molecular Structure
• Signal Transduction (drug effects)