Mannotriose‑containing extract of <em>Streptomyces sennicomposti</em> GMY01 induces the apoptosis of HeLa cells and exhibits binding affinity with BCL‑2 and MCL‑1 proteins

Pasala,Metamalik; Damayanti,Ema; Widada,Jaka; Pratiwi,Woro Rukmi; Mustofa,Mustofa

doi:10.3892/wasj.2025.372

September-October 2025 Volume 7 Issue 5

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September-October 2025 Volume 7 Issue 5

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

Authors:
- Metamalik Pasala
- Ema Damayanti
- Jaka Widada
- Woro Rukmi Pratiwi
- Mustofa Mustofa
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Affiliations: Department of of Pharmacology and Therapy, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia, Research Center for Food Technology and Processing, National Research and Innovation Agency (BRIN), Gunungkidul, Yogyakarta 55861, Indonesia, Department of Agricultural Microbiology, Faculty of Agriculture, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia

Copyright: © Pasala et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
Article Number: 84
|
Published online on: July 4, 2025

https://doi.org/10.3892/wasj.2025.372
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Abstract

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 IC₅₀ value 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 0.5xIC₅₀ levels, P=0.99; and 2.99±0.27 compared to 4.01±0.39 at 1xIC₅₀ levels, 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.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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