Cytotoxic activity of isoniazid derivative in human breast cancer cells
Background/Aim: Isoniazid is an antibiotic used for the treatment of tuberculosis. Previously, we found that the isoniazid derivative (E)-N'-(2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) could be developed as novel antimycobacterial agent by lead optimization. We further explored t...
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my.um.eprints.285812022-03-28T07:08:07Z http://eprints.um.edu.my/28581/ Cytotoxic activity of isoniazid derivative in human breast cancer cells Barathan, Muttiah Zulpa, Ahmad Khusairy Vellasamy, Kumutha Malar Mariappan, Vanitha Shivashekaregowda, Naveen Kumar Hawala Ibrahim, Zaridatul Aini Vadivelu, Jamuna QR Microbiology R Medicine RM Therapeutics. Pharmacology Background/Aim: Isoniazid is an antibiotic used for the treatment of tuberculosis. Previously, we found that the isoniazid derivative (E)-N'-(2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) could be developed as novel antimycobacterial agent by lead optimization. We further explored the ability of this compound compared to zerumbone in inhibiting the growth of MCF-7 breast cancer cells. Materials and Methods: Cytotoxicity was measured by the MTT assay and further confirmed via apoptosis, ROS, cell cycle, DNA fragmentation and cytokine assays. Results: ITHB4 demonstrated a lower IC50 compared to zerumbone in inhibiting the proliferation of MCF-7 cells. ITHB4 showed no toxicity against normal breast and human immune cells. Apoptosis assay revealed that ITHB4, at a concentration equal to the IC50, induces apoptosis of MCF-7 cells and cell cycle arrest at the sub-G1 and G(2)/M phases. ITHB4 triggered accumulation of intracellular ROS and nuclear DNA fragmentation. Secretion of pro-inflammatory cytokines induced inflammation and potentially immunogenic cell death. Conclusion: ITHB4 has almost similar chemotherapeutic properties as zerumbone in inhibiting MCF-7 growth, and hence provide the basis for further experiments in animal models. INT INST ANTICANCER RESEARCH 2021 Article PeerReviewed Barathan, Muttiah and Zulpa, Ahmad Khusairy and Vellasamy, Kumutha Malar and Mariappan, Vanitha and Shivashekaregowda, Naveen Kumar Hawala and Ibrahim, Zaridatul Aini and Vadivelu, Jamuna (2021) Cytotoxic activity of isoniazid derivative in human breast cancer cells. In Vivo, 35 (5). pp. 2675-2685. ISSN 0258-851X, DOI https://doi.org/10.21873/invivo.12551 <https://doi.org/10.21873/invivo.12551>. 10.21873/invivo.12551 |
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QR Microbiology R Medicine RM Therapeutics. Pharmacology Barathan, Muttiah Zulpa, Ahmad Khusairy Vellasamy, Kumutha Malar Mariappan, Vanitha Shivashekaregowda, Naveen Kumar Hawala Ibrahim, Zaridatul Aini Vadivelu, Jamuna Cytotoxic activity of isoniazid derivative in human breast cancer cells |
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Background/Aim: Isoniazid is an antibiotic used for the treatment of tuberculosis. Previously, we found that the isoniazid derivative (E)-N'-(2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) could be developed as novel antimycobacterial agent by lead optimization. We further explored the ability of this compound compared to zerumbone in inhibiting the growth of MCF-7 breast cancer cells. Materials and Methods: Cytotoxicity was measured by the MTT assay and further confirmed via apoptosis, ROS, cell cycle, DNA fragmentation and cytokine assays. Results: ITHB4 demonstrated a lower IC50 compared to zerumbone in inhibiting the proliferation of MCF-7 cells. ITHB4 showed no toxicity against normal breast and human immune cells. Apoptosis assay revealed that ITHB4, at a concentration equal to the IC50, induces apoptosis of MCF-7 cells and cell cycle arrest at the sub-G1 and G(2)/M phases. ITHB4 triggered accumulation of intracellular ROS and nuclear DNA fragmentation. Secretion of pro-inflammatory cytokines induced inflammation and potentially immunogenic cell death. Conclusion: ITHB4 has almost similar chemotherapeutic properties as zerumbone in inhibiting MCF-7 growth, and hence provide the basis for further experiments in animal models. |
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Article |
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Barathan, Muttiah Zulpa, Ahmad Khusairy Vellasamy, Kumutha Malar Mariappan, Vanitha Shivashekaregowda, Naveen Kumar Hawala Ibrahim, Zaridatul Aini Vadivelu, Jamuna |
author_facet |
Barathan, Muttiah Zulpa, Ahmad Khusairy Vellasamy, Kumutha Malar Mariappan, Vanitha Shivashekaregowda, Naveen Kumar Hawala Ibrahim, Zaridatul Aini Vadivelu, Jamuna |
author_sort |
Barathan, Muttiah |
title |
Cytotoxic activity of isoniazid derivative in human breast cancer cells |
title_short |
Cytotoxic activity of isoniazid derivative in human breast cancer cells |
title_full |
Cytotoxic activity of isoniazid derivative in human breast cancer cells |
title_fullStr |
Cytotoxic activity of isoniazid derivative in human breast cancer cells |
title_full_unstemmed |
Cytotoxic activity of isoniazid derivative in human breast cancer cells |
title_sort |
cytotoxic activity of isoniazid derivative in human breast cancer cells |
publisher |
INT INST ANTICANCER RESEARCH |
publishDate |
2021 |
url |
http://eprints.um.edu.my/28581/ |
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1735409559822925824 |
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13.160551 |