The Cytotoxic and Anti-tumor Potential of Methanolic Extracts of Indian Marine Isolates in HCT116 Colorectal Cancer Cells

Introduction: The marine environment is a rich source of biodiversity, with several of its inhabitants producing unique and physiologically active substances. The use of marine bacterial-derived chemicals over traditional pharmaceuticals is gaining traction due to their larger variety of targets and modes of action. To circumvent the drawbacks of current therapy options, researchers have looked to marine microbes for novel and effective anti-cancer compounds. In this study, we examine one of India's least-examined coastal areas in search of novel bacterial sources of anti-cancer chemicals. Method: Soil sediments from the Indian south coast region were collected and microbes were isolated using standard methods. The microorganisms were identified using 16s rRNA sequencing, and cytotoxic extracts were further examined using GC-MS. MTT, clonogenic, and spheroid tests assessed the extract's cytotoxicity and anti-tumor efficacy. Results: Our results indicated that the bacterial isolates with potent cytotoxic activity were Bacillus drentensis and Bacillus haikouensis and had 10 and 12 potent anti-cancer and other bioactive compounds. The extracts had an IC50 of 30.08 and 109.4 μg/ml in the HCT116 cell line, respectively, and strongly inhibited colony formation. The cell cycle analysis indicated that the extract induced cell death as indicated by the subG0 peak. We also showed that these methanolic extracts induced toxicity in a 3D spheroid model indicating a strong anti-tumor activity. Furthermore, we performed molecular docking for the compounds present in the extracts to VEGFR and nucleolin and found that ergostane had favorable binding energy only to VEGFR. Conclusion: The results indicate that the ME of B. drentensis and B. haikouensis contains potent anti-cancer compounds to exhibit cytotoxic and anti-tumor activity in colorectal cancer cells.