Abstract
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 (IC50 value of 18.41–231.6 µg/ml), whereas the IC50 value 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 (C12H21N3 O4 ), 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.
Highlights
Lung cancer is a type of cancer with the highest incidence after prostate cancer in men and after breast cancer in women (Dela Cruz et al, 2011)
We studied the cytotoxicity of Streptomyces sp
Human lung cancer cell line A549 was obtained from the Department of Cancer Cell Biology, Faculty of Pharmaceutical Sciences, University of Toyama, Japan
Summary
Lung cancer is a type of cancer with the highest incidence after prostate cancer in men and after breast cancer in women (Dela Cruz et al, 2011). The Streptomyces bacteria are the main source of medicinal compounds derived from microbes for nearly 80% of drugs, especially antibiotics (Weber et al, 2015) and anticancer agents (Dhaneesha et al, 2017; Nguyen et al, 2020). GMY01, which has a very high potential active principle to be Damayanti et al / Journal of Applied Pharmaceutical Science 11 (06); 2021: 046-055 developed as a therapeutic agent (Herdini et al, 2015). This bacterial extract was found to contain anticancer activities against T47D and MCF7 breast cancer cell lines (Farida et al, 2007; Werdyani et al, 2017)
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