Cytotoxic activity of isoniazid derivative in human breast cancer cells

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

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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.

Item Type: Article
Funders: Fundamental Research Grant Scheme (FRGS) from Ministry of Education (MOE)
Uncontrolled Keywords: Apoptosis; Synthetic compound; Reactive oxygen species; Cytokine; Zerumbone; Isoniazid; Breast cancer cells
Subjects: Q Science > QR Microbiology
R Medicine
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Medicine > School of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 28 Mar 2022 07:08
Last Modified: 28 Mar 2022 07:08

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