Bishydroquinone Renieramycin M Induces Apoptosis of Human Lung Cancer Cells Through a Mitochondria-dependent Pathway.

Abstract

BACKGROUND:

Renieranycin M (RM), a bistetrahydro-isoquinolinequinone isolated from the Thai blue sponge, Xestospongia sp. was reported to be a potent anti-lung cancer agent. Modification at quinone ring enhanced apoptosis over necrosis. Thus, bishydroquinone renieramycin M (HQ-RM) was prepared and evaluated for apoptosis induction in lung cancer cells.

METHODS:

HQ-RM was examined for cytotoxicity and apoptosis induction in human lung cancer H292 cells by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazoliumbromide and Hoechst/propidium iodide staining, respectively. The key molecular markers of mitochondrial apoptosis pathway were determined by western blot analysis.

RESULTS:

HQ-RM exhibited stronger cytotoxicity than RM. HQ-RM reduced vitality of lung cancer cells in a dose-dependent manner. Nuclear staining assay indicated that apoptotic cell death was the main mechanism of toxicity caused by HQ-RM. Protein analysis revealed that HQ-RM-mediated apoptosis involved the increase of pro-apoptotic B-cell lymphoma 2 associated X (BAX) protein, and the decrease of anti-apoptosis myeloid cell leukemia 1 (MCL1) and B-cell lymphoma 2 (BCL2) proteins. Moreover, caspase-9 and -3 and Poly (ADP-ribose) polymerase (PARP) were dramatically cleaved in response to HQ-RM treatment.

CONCLUSION:

HQ-RM has highly potent anticancer activity, greater than its parental RM, and induces lung cancer cell apoptosis through a mitochondrial apoptosis caspase-dependent mechanism. This information benefits the development of this compound for cancer therapy.

• Authors: Tatchakorn Pinkhien, Arnatchai Maiuthed, Supakarn Chamni, Khanit Suwanborirux, Naoki Saito, Pithi Chanvorachote
• Journal: Anticancer research (Anticancer Res) Vol. 36 Issue 12 Pg. 6327-6333 (12 2016) ISSN: 1791-7530 [Electronic] Greece
• PMID: 27919953 (Publication Type: Journal Article)
• Copyright: Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Tetrahydroisoquinolines
• renieramycin M

Topics

• Apoptosis (drug effects)
• Cell Line, Tumor
• Humans
• Lung Neoplasms (pathology)
• Mitochondria (drug effects, metabolism)
• Tetrahydroisoquinolines (pharmacology)