PT - JOURNAL ARTICLE AU - NATTANAN LOSUWANNARAK AU - BOONCHOO SRITULARAK AU - PITHI CHANVORACHOTE TI - Cycloartobiloxanthone Induces Human Lung Cancer Cell Apoptosis <em>via</em> Mitochondria-dependent Apoptotic Pathway DP - 2018 Jan 01 TA - In Vivo PG - 71--78 VI - 32 IP - 1 4099 - http://iv.iiarjournals.org/content/32/1/71.short 4100 - http://iv.iiarjournals.org/content/32/1/71.full SO - In Vivo2018 Jan 01; 32 AB - 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.