Mannotriose-containing extract of Streptomyces sennicomposti GMY01 induces the apoptosis of HeLa cells and exhibits binding affinity with BCL-2 and MCL-1 proteins

Streptomyces sennicomposti (S. sennicomposti) GMY01 is known to exhibit anticancer activity and mannotriose has been identified as an active compound. The present study aimed to determine the anticancer activity of a mannotriose-containing fraction of GMY01 on cervical cancer and apoptosis regulatory proteins (BCL-2 and MCL-1). For this purpose, an in vitro assay was conducted using HeLa cells as a cancer cell line and C2C12 cells as a normal cell line. In addition, in silico molecular docking was performed to determine the binding of mannotriose of S. sennicomposti GMY01 with BCL-2 and MCL-1. Methanol extract (ME) containing mannotriose was extracted from the cell-free supernatant of GMY01 fermentation culture and the n-hexane-free methanol fraction (HMF) was obtained by the fractionation of the methanol extract using n-hexane solvent. The results revealed that the IC50value of the HMF was lower than that of the ME; however, the difference was not statistically significant (78.82 compared to 93.75 µg/ml; P=0.843). The selectivity index of HMF was higher than ME (117.04 compared to 6.23). Moreover, the apoptotic index of the HMF was lower than that of the ME; however, the difference was not statistically significant (2.32±0.48 compared to 2.33±0.44 at 0.5xIC50levels, P=0.99; and 2.99±0.27 compared to 4.01±0.39 at 1xIC50levels, P=0.151). In the In silico molecular docking analysis, mannotriose of S. sennicomposti GMY01 was found to bind to BCL-2 and MCL-1 (highest affinity: -1.10 and -1.33 kcal/mol, respectively). On the whole, the present study demonstrates that HMF containing mannotriose exerts a moderate cytotoxic effect and a high selectivity index on HeLa cells and binds to apoptotic regulatory proteins. Copyright © 2025 Pasala et al. This work is licensed under a Creative Commons Attribution 4. 0 International (CC BY 4.0) License.