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Effects of the Combination of Gliotoxin and Adriamycin on the Adriamycin-Resistant Non-Small-Cell Lung Cancer A549 Cell Line

School of Biomaterial Science and Technology, College of Applied Life Sciences, Jeju National University, Jeju 63243, Korea
Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju 63243, Korea
Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Mar. Drugs 2018, 16(4), 105;
Received: 7 February 2018 / Revised: 17 March 2018 / Accepted: 24 March 2018 / Published: 27 March 2018
(This article belongs to the Collection Marine Compounds and Cancer)
PDF [12896 KB, uploaded 3 May 2018]


Acquired drug resistance constitutes an enormous hurdle in cancer treatment, and the search for effective compounds against resistant cancer is still advancing. Marine organisms are a promising natural resource for the discovery and development of anticancer agents. In this study, we examined whether gliotoxin (GTX), a secondary metabolite isolated from marine-derived Aspergillus fumigatus, inhibits the growth of adriamycin (ADR)-resistant non-small-cell lung cancer (NSCLC) cell lines A549/ADR. We investigated the effects of GTX on A549/ADR cell viability with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the induction of apoptosis in A549/ADR cells treated with GTX via fluorescence-activated cell sorting analysis, Hoechst staining, annexin V/propidium iodide staining, tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and western blotting. We found that GTX induced apoptosis in A549/ADR cells through the mitochondria-dependent pathway by disrupting mitochondrial membrane potential and activating p53, thereby increasing the expression levels of p21, p53 upregulated modulator of apoptosis (PUMA), Bax, cleaved poly (ADP-ribose) polymerase (PARP), and cleaved caspase-9. More importantly, we discovered that GTX works in conjunction with ADR to exert combinational effects on A549/ADR cells. In conclusion, our results suggest that GTX may have promising effects on ADR-resistant NSCLC cells by inducing mitochondria-dependent apoptosis and through the combined effects of sequential treatment with ADR. View Full-Text
Keywords: gliotoxin; NSCLC; adriamycin resistance; apoptosis gliotoxin; NSCLC; adriamycin resistance; apoptosis

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Manh Hung, L.V.; Song, Y.W.; Cho, S.K. Effects of the Combination of Gliotoxin and Adriamycin on the Adriamycin-Resistant Non-Small-Cell Lung Cancer A549 Cell Line. Mar. Drugs 2018, 16, 105.

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