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 (IC 50 value of 18.41-231.6 µg/ml), whereas the IC 50 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 (C 25 H 42 O 6 ), vazabitide A (C 12 H 21 N 3 O 4 ), albaflavenone (C 15 H 22 O), grincamycin (C 49 H 62 O 18 ), isorenieratene (C 40 H 48 ), geosmin (C 12 H 22 O), hopene (C 30 H 50 ), and saframycin A (C 60 H 68 N 10 O 14 ). 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 (C 49 H 62 O 18 ) 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.

Marine-Derived Streptomyces sennicomposti GMY01 with Anti-Plasmodial and Anticancer Activities: Genome Analysis, In Vitro Bioassay, Metabolite Profiling, and Molecular Docking

“…Mannotriose, and N-acetylneuraminyl-(2,6)-galactose have a higher affinity to autophagy proteins. These results were similar to the anticancer activity of S. sennicomposti GMY01 on the lung cancer cell line in the previous study [ 69 ]. The analysis of protein expression using Western blot after treatment with GMY01 extract showed that the LC3-I and LC3-II autophagy-related protein expressions were higher than PARP apoptosis-related proteins [ 69 ].…”

Isolation of active compounds from Streptomyces sennicomposti GMY01 and cytotoxic activity on breast cancer cells line

“…bacteria which was cultured in SNB media produced sericin compounds that were proven to have cytotoxic activity in several cancer cell cultures, which were Caco-2, MCF-7, and A549 cells [ 21 ]. In a previous study, an extract of S. sennicomposti GMY01 which was fermented using SNB medium showed anticancer activity on human cancer cell line A549 [ 12 ].…”

“…A total of 30 mL (10 % v/v) of 3 days inoculum culture was inoculated in 300 mL of Starch Nitrate Broth (SNB) media using a 500 mL Erlenmeyer tube, then incubated on a rotary shaker incubator at 200–250 rpm for 11 days at room temperature (25–30 °C). The SNB medium contained 0.5 g of NaCl, 1 g of KNO3, 0.5 g of K2HPO4, 0.5 g of MgSO4·7H2O, 0.01 g of FeSO4·7H2O, and 20 g of soluble starch in 1000 mL of distilled water [ 12 ]. The secondary metabolite was obtained by separating the cell biomass from the liquid culture using centrifugation at 3000 rpm for 15 min.…”

Draft Genome Sequence of the Marine-Derived, Anticancer Compound-Producing Bacterium Streptomyces sp. Strain GMY01

“…The novel Streptomyces strain GMY01 was isolated from a marine sediment sample from Krakal Beach (Yogyakarta, Indonesia; 8°8′44″S, 110°35′59″E) ( 5 ). Strain GMY01 has high anticancer activity in lung cancer cells (A549) ( 6 ). In this study, we present the annotated genome sequence of the bacterium GMY01 and report the potential active compounds encoded by its biosynthetic gene clusters.…”