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Πέμπτη 19 Αυγούστου 2021

Cytotoxic Activity of Isoniazid Derivative in Human Breast Cancer Cells

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In Vivo. 2021 Sep-Oct;35(5):2675-2685. doi: 10.21873/invivo.12551.

ABSTRACT

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 MC F-7 cells and cell cycle arrest at the sub-G1 and G2/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.

PMID:34410956 | DOI:10.21873/invivo.12551

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