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Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Systemic study of selected histone deacetylase inhibitors in cardiac complications associated with cancer cachexia
Vivek Bora1, Dhwani Patel1, Kaid Johar2
1Department of Pharmacology, Institute of Pharmacy, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad, Gujarat 382481, India.
Abstract:
Cancer cachexia is mainly characterized by wasting of skeletal muscles and fat and body weight loss, along with severe complications of major organs like liver, heart, brain and bone. There can be diminishing performance of these major organs as cancer cachexia progresses, one such drastic effect on the cardiac system. In the present study, differential effect of histone deacetylase inhibitors (HDACi) on cardiac complications associated with cancer cachexia is studied. Two models were used to induce cancer cachexia: B16F1 induced metastatic cancer cachexia and Lewis lung carcinoma cell - induced cancer cachexia. Potential of Class I HDACi entinostat, Class II HDACi MC1568, and nonspecific HDACi sodium butyrate on cardiac complications were evaluated using the cardiac hypertrophy markers, hemodynamic markers, and cardiac markers along with histopathological evaluation of heart sections by Periodic acid-Schiff staining, Masson's trichrome staining, Picro-sirius red staining, and haematoxylin and eosin staining. Immunohistochemistry evaluation by vimentin and caspase 3 protein expression was evaluated. Entinostat showed promising results by attenuating the cardiac complications, and MC1568 treatment further exacerbated the cardiac complications, while non-conclusive effect were recorded after treatment with sodium butyrate. This study will be helpful in evaluating other HDACi for potential in cardiac complications associated with cancer cachexia.
Insights
Histone deacetylase inhibitors (HDACi) show differential effects on cancer cachexia cardiac complications. Entinostat attenuated cardiac issues, while MC1568 worsened them, indicating potential therapeutic strategies.
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- Cancer cachexia leads to significant weight loss and organ dysfunction, particularly affecting the heart.
- Cardiac complications in cancer cachexia can diminish major organ performance.
Purpose of the Study:
- To investigate the differential effects of histone deacetylase inhibitors (HDACi) on cardiac complications in cancer cachexia models.
- To evaluate the therapeutic potential of specific HDAC inhibitors in mitigating cancer-related cardiac dysfunction.
Main Methods:
- Utilized two cancer cachexia models: B16F1 metastatic and Lewis lung carcinoma.
- Assessed cardiac hypertrophy, hemodynamic, and cardiac markers, alongside histopathological and immunohistochemical analyses (Periodic acid-Schiff, Masson's trichrome, Picro-sirius red, H&E, vimentin, caspase 3).
- Tested Class I HDACi (entinostat), Class II HDACi (MC1568), and a non-specific HDACi (sodium butyrate).
Main Results:
- Entinostat (Class I HDACi) demonstrated promising results in attenuating cardiac complications.
- MC1568 (Class II HDACi) treatment exacerbated cardiac complications.
- Sodium butyrate (non-specific HDACi) showed non-conclusive effects on cardiac complications.
Conclusions:
- Entinostat exhibits potential as a therapeutic agent for cardiac complications in cancer cachexia.
- Targeting specific HDAC classes may offer distinct outcomes in managing cancer cachexia-related cardiac dysfunction.
- Further evaluation of HDAC inhibitors is warranted for their role in cancer cachexia cardiac complications.
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