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01-11-2024 | Original Paper

Polydatin inhibits histone deacetylase 1 and shows an anti-angiogenic action in head and neck squamous cell carcinoma

Authors: Aadil Manzoor Baba, Altaf Ahmad Shah, Imren Bayil, Satyabrata Nayak, Ritis Kumar Shyanti, Najma Nissa, Mansha Muzaffar, Mohammad Amin Hajam, Rezwan Akhtar, Bashir Ahmad Malla, Salman Akhtar, Rana P. Singh, Nazir Ahmad Dar

Published in: Medical Oncology | Issue 11/2024

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Abstract

Polydatin, a natural derivative of resveratrol, has shown many anticancer properties. However, the underlying mechanisms of its anticancer properties including its effect on the epigenetic landscape are not well understood. Here, we explored the effect of polydatin on histone deacetylase 1 (HDAC1) activity. We used in silico approaches to assess the possible binding of polydatin to the active site pockets of HDAC1 and in vitro approaches to test the potential effects of the interaction on its enzymatic activity. As compared to SAHA, an approved drug, the polydatin showed stronger and stable binding to the HDAC1. The binding energy, conformational changes, formation of extra hydrogen bonding, and other interactions within and outside the active site all favour largely stable and strong polydatin binding to the enzyme. Further, the ADME and toxicity prediction values are encouraging for the evaluation of polydatin as a drug. The laboratory leg of the study substantiated that the polydatin binding was strong and stable enough to inhibit HDAC1 activity in UMS-CC-22B cells as demonstrated by an increase in H3K9 acetylation. In addition, polydatin treated cells showed attenuated proliferation. The in vitro tube formation and migration by HUVEC and UM-SCC-22B cells were inhibited by polydatin. The decreased tube formation due to HDAC1 inhibition is possibly due to up-regulation of the anti-angiogenic gene - TSP1 in UM-SCC-22B cells. As compared to SAHA, more promising results were shown both in its computational calculations and on the cell physiology features. Stronger and stable binding, more anti-proliferative and anti-angiogenic potential were observed with respect to polydatin. Further, the cell death was more pronounced with SAHA treatment. Therefore, polydatin might be a better anticancer drug and can have a potential to replace SAHA in combinational therapeutic regimen.
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Metadata
Title
Polydatin inhibits histone deacetylase 1 and shows an anti-angiogenic action in head and neck squamous cell carcinoma
Authors
Aadil Manzoor Baba
Altaf Ahmad Shah
Imren Bayil
Satyabrata Nayak
Ritis Kumar Shyanti
Najma Nissa
Mansha Muzaffar
Mohammad Amin Hajam
Rezwan Akhtar
Bashir Ahmad Malla
Salman Akhtar
Rana P. Singh
Nazir Ahmad Dar
Publication date
01-11-2024
Publisher
Springer US
Published in
Medical Oncology / Issue 11/2024
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-024-02490-7

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