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Analysis of the Anticancer Mechanism of OR3 Pigment from Streptomyces coelicolor JUACT03 Against the Human Hepatoma Cell Line Using a Proteomic Approach

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Abstract

This study assessed OR3 pigment, derived from Streptomyces coelicolor JUACT03, for its anticancer potential on HepG2 liver cancer cells and its safety on HEK293 normal cells. OR3 induced apoptosis and inhibited HepG2 cell proliferation, confirmed by caspase activation, Sub-G1 phase cell cycle arrest, and reduced colony formation. Proteomic analysis revealed altered expression of proteins associated with ribosomal function, mRNA processing, nuclear transport, proteasome activity, carbohydrate metabolism, chaperone function, histone regulation, and vesicle-mediated transport. Downregulation of proteins in MAPKAP kinase1, EIF2, mTOR, and EIF4 pathways contributed to apoptosis and cell cycle arrest. Changes in c-MYC, FUBP1 target proteins and upregulation of Prohibitin-1 (PHB1) were also noted. Western blot analysis supported alterations in eIF2, mTOR, and RAN pathways, including downregulation of RAB 5, c-MYC, p38, MAPK1, and MAPK3. OR3 exhibited significant anti-angiogenic activity in the in ovo CAM assay. In summary, OR3 demonstrated strong anticancer effects, inducing apoptosis, hindering proliferation, and displaying antiangiogenic properties. These findings highlight OR3’s potential as an anticancer drug candidate, warranting further in vivo exploration.

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Data Availability

All the data that support the findings of this current study are included in this article and the mass spectrometry-based proteomics data have been deposited in the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD043439.

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Acknowledgements

The JRF fellowship granted to the research scholar, S.D., by Council of Scientific and Industrial Research (CSIR), India is greatly acknowledged. The authors would like to acknowledge the infrastructural facilities provided by JAIN (Deemed to be University), Bengaluru, for carrying out the research work.

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Conceptualization: V.K.N.; Methodology: V.K.N. and S.D.; Formal analysis and investigation: S.D.; Supervision: V.K.N.; Writing—original draft preparation: S.D.; Writing—review and editing: V.K.N.; all authors reviewed and approved the manuscript.

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Correspondence to Varalakshmi Kilingar Nadumane.

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Derangula, S., Nadumane, V.K. Analysis of the Anticancer Mechanism of OR3 Pigment from Streptomyces coelicolor JUACT03 Against the Human Hepatoma Cell Line Using a Proteomic Approach. Cell Biochem Biophys (2024). https://doi.org/10.1007/s12013-024-01258-0

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