Damayanti, Ema and Nisa, Khoirun and Handayani, Sri and Dewi, Rizna Triana and Mustofa, M. and Dinoto, Achmad and Widada, Jaka (2021) Cytotoxicity and Molecular Mechanism of Marine-derived Streptomyces Sp. Gmy01 on Human Lung Cancer Cell Line A549. Journal of Applied Pharmaceutical Science, 11 (6). 046 – 055. ISSN 22313354
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Marine-derived Streptomyces sp. GMY01 is a biotechnologically potential bacterium which has anticancer activity. This research aimed to investigate the anticancer activity of GMY01 extract on human lung cancer cell line A549 and its mechanism using Western blot analysis and in silico molecular docking. Ethyl acetate extract was obtained from the supernatant of an 11-day fermented product and it was fractionated using flash chromatography. An in vitro assay of the selected fractions (F5, F6, F7, F8, and F14) on the A549 cell line showed moderate activity (IC50value of 18.41–231.6 μg/ml), whereas the IC50value of the crude extract (CE) was 34.26 μg/ml. Western blot analysis revealed the mode of action of GMY01 fractions F6 and F7 to be that of an autophagy induction mechanism, similar to that of the CE. Targeted liquid chromatography high-resolution mass spectrometry analysis of GMY01 extract detected eight compounds: herboxidiene (C25H42O6), vazabitide A (C12H21N3O4), albaflavenone (C15H22O), grincamycin (C49H62O18), isorenieratene (C40H48), geosmin (C12H22O), hopene (C30H50), and saframycin A (C60H68N10O14). A molecular docking study on target proteins of antiapoptotic proteins (BCL-2 and BCL-XL) and autophagy proteins mammalian target of rapamycin (mTOR-C1 and mTORC2) showed that these compounds had a high affinity. Among all the compounds, grincamycin (C49H62O18) had the highest affinity on antiapoptotic proteins (−11.8 and −10.4) and on autophagy proteins (−12.1 and −11.5) within all binding domains. These results indicate that Streptomyces sp. GMY01 has a promising anticancer agent, grincamycin, for human lung cancer. © 2021 Ema Damayanti et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Item Type: | Article |
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Additional Information: | Cited by: 6; All Open Access, Gold Open Access |
Uncontrolled Keywords: | Anticancer; lung cancer cell; marine Streptomyces; targeted LC-HRMS; molecular docking |
Subjects: | R Medicine > RS Pharmacy and materia medica |
Divisions: | Faculty of Pharmacy |
Depositing User: | Sri JUNANDI |
Date Deposited: | 24 Sep 2024 08:19 |
Last Modified: | 24 Sep 2024 08:19 |
URI: | https://ir.lib.ugm.ac.id/id/eprint/4716 |