Abstract
During our previous investigation, bioactive compounds present in the extract of Streptomyces sp. strain 196 were characterized using LC–MS/MS and 1H NMR studies. These compounds were K-252-C aglycone indolocarbazole alkaloid, decoyinine, and cycloheximide; the study of these natural drugs against lung carcinoma is still limited. Focus of the current investigation was to study the anticancer effect of strain 196 extract on lung cancer cells (A549). During in vitro studies, anti-proliferative effect of extract was studied using MTT assay in A549 cells. Effect of extract on cell survival was further evaluated using colony assay. Cell death was qualitatively assessed using apoptosis assay. The aftereffect of extract treatment on metastatic potential of cancerous cells was studied using wound closure assay. Effect of extract on the morphology and cytoskeletal arrangement of A549 cells was studied using phalloidin staining. The extract demonstrated concentration and time-dependent cytotoxicity with IC50 value at 0.5 mg/ml (6 h) and 0.15 mg/ml (24 h). The proliferation and metastatic potential of cells, as characterized by MTT and migration assay, decreased over time in a concentration-dependent manner. Discrete changes in cellular morphology were noted as a result of the induced cytotoxicity. Apoptosis assay demonstrated 98.7% cell death at highest concentration of extract (1 mg/ml). During in silico studies, molecular docking revealed that strain 196 compounds are efficiently binding to mutant EGFR form (T790M/L858R) with release of binding energy (∆G) between − 5 and − 6.9 kcal/Mol. In conclusion, strain 196 extract could be a source of therapeutic drugs to treat lung carcinoma.
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Acknowledgements
We thank the National Centre for Cell Science (NCCS), Pune, for providing cell lines. Acharya Narendra Dev College (ANDC), University of Delhi is warmly acknowledged for providing infrastructural facilities. We are also thankful to Dr. Swati Midha (DST-Inspire faculty, Special Centre for Nanoscience, JNU), Km. Anjaly (JNU), Ms. Neha Verma (JNU), Mr. Ravi Kumar (JNU) and Mr. Shani Kumar (University of Delhi) for their valuable suggestions.
Funding
This study was funded by Council of Scientific & Industrial Research (CSIR), Government of India (grant numbers 08/529(0007)/2017-EMR-I and 08/529(0005)/2017-EMR-I).
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PK, AC, MK, BKK and MKK conceived and designed the experiments. PK and AC performed all experiments. PK analyzed the data reported in this study. PK, AC, MK, BKK, AK, RS, and MKK contributed in writing. All authors read and approved the manuscript.
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Kumar, P., Chauhan, A., Kumar, M. et al. In vitro and in silico anticancer potential analysis of Streptomyces sp. extract against human lung cancer cell line, A549. 3 Biotech 11, 254 (2021). https://doi.org/10.1007/s13205-021-02812-w
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DOI: https://doi.org/10.1007/s13205-021-02812-w