Cytotoxicity and Molecular Mechanism of Marine-derived Streptomyces Sp. Gmy01 on Human Lung Cancer Cell Line A549

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 (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.