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Mar. Drugs 2018, 16(4), 105; https://doi.org/10.3390/md16040105

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

1
School of Biomaterial Science and Technology, College of Applied Life Sciences, Jeju National University, Jeju 63243, Korea
2
Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju 63243, Korea
3
Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
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)
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Abstract

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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