Anticancer Effect of Marine Sponge-Associated Bacillus pumilus AMK1 Derived Dipeptide Cyclo (-Pro-Tyr) in Human Liver Cancer Cell Line Through Apoptosis and G2/M Phase Arrest

The present study was initiated to identify a novel cytotoxic bioactive molecule from marine sponge Callyspongia fistularis symbionts and to investigate its apoptotic role on human liver cancer cell line (HepG2). The extracts of all the isolated strains (AMK1–AMK12) from sponge Callyspongia fistularis were screened based on cytotoxicity on HepG2 cell line, among them AMK1 showed the significant cytotoxic activity. The strain AMK1 was identified as Bacillus pumilus based on 16S rRNA sequencing and biochemical tests. Further purifying the bio-molecules responsible for the cytotoxic activity by different spectral analysis led to the identification of dipeptide Cyclo(-Pro-Tyr), that showed promising cytotoxic activity and apoptotic inducing activity on HepG2 liver cancer cell line with an IC50 value of 42.98 µg/mL. The effect of Cyclo(-Pro-Tyr) induced apoptosis of HepG2 cells was indicated by nuclear morphology, PI staining, AO/EB staining and cell cycle arrest by flow cytometry analysis. These findings suggest that Cyclo(-Pro-Tyr) isolated from B.pumilus AMK1 may contribute as a novel anticancer molecule, forming an important strategy for developing alternative therapies to treat liver cancer with natural molecule without affecting the normal cells.