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Apoptotic mechanisms of myricitrin isolated from Madhuca longifolia leaves in HL-60 leukemia cells

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Abstract

Myricitrin, a naturally occurring flavonoid in Madhuca longifolia, possesses several medicinal properties. Even though our earlier work revealed its role against the proliferation of acute myelogenous leukemia cells (HL-60), its molecular mechanisms have not yet been revealed. The current study aims to explore the molecular mechanisms of myricitrin (isolated from an ethnomedicinal drug Madhuca longifolia) to induce apoptosis in HL-60 cells. Treatment with IC-50 dose of myricitrin (353 µM) caused cellular shrinkage and cell wall damage in HL-60 cells compared to untreated control cells. Myricitrin treatment reduced the mitochondrial membrane potential (22.95%), increased DNA fragmentation (90.4%), inhibited the cell survival proteins (RAS, B-RAF, & BCL-2) and also induced pro-apoptotic proteins (p38, pro-caspase-3, pro-caspase-9 and caspase-3) in the HL-60 cells. The present study provides scientific evidence for the apoptosis caused by myricitrin in HL-60 leukemia cells. Hence, the phytochemical myricitrin could be considered as a potential candidate to develop an anticancer drug after checking its efficacy through suitable pre-clinical and clinical studies.

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Data Availability

The data and materials of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

Authors are also grateful to the Honorable Vice-Chancellor, SASTRA Deemed University for provided the necessary support.

Funding

Authors are thankful to NMPB-AYUSH (Grant No. R&D/TN-03/2016–17) for the financial support.

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Authors

Contributions

Mr. MKS has performed the in vitro experiments, acquisition and analysis of data, and writing the manuscript draft. Ms. AK and Mr. AJ have provided technical support for in vitro experiments especially western blotting and acquisition of data. Mr. KS helped to perform in silico studies. Dr. VV has contributed in experimental design, supervision, conceptualization, project administration and manuscript writing. Dr. SKM has conceptualized and designed the experiments, analyzed the data, manuscript writing and contributed reagents/materials/analysis tools.

Corresponding authors

Correspondence to Vellingiri Vadivel or Santanu Kar Mahapatra.

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Sarkar, M.K., Kar, A., Jayaraman, A. et al. Apoptotic mechanisms of myricitrin isolated from Madhuca longifolia leaves in HL-60 leukemia cells. Mol Biol Rep 48, 5327–5334 (2021). https://doi.org/10.1007/s11033-021-06500-z

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