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  • Title: Cycloartobiloxanthone Induces Human Lung Cancer Cell Apoptosis via Mitochondria-dependent Apoptotic Pathway.
    Author: Losuwannarak N, Sritularak B, Chanvorachote P.
    Journal: In Vivo; 2018; 32(1):71-78. PubMed ID: 29275301.
    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.
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