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 IC 50 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 IC 50, 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.Breast cancer is the most frequent cancer among women, impacting 2.1 million women each year (1). In 2020, the GLOBOCAN report indicated that 24.5% of cancer cases among females belong to breast cancer, and estimated that 684,996 women died from breast cancer (1). While breast cancer rates are higher among women in more developed regions, rates are predicted to increase in nearly every region globally. Early diagnosis and aggressive treatment/prevention strategies such as surgery in combination with chemotherapy and radiotherapy are the current clinical approaches to combat this disease (2). However, tumor recurrence remains a major problem in the treatment of breast cancer. Moreover, the broad-spectrum actions of chemotherapy and radiotherapy agents that are not selective in killing cancer cells cause many unwanted side effects in patients (3). Hence, these called for urgent measures and innovations in anti-cancer therapy to effectively treat this disease.In recent years, there is an emerging research on developing novel synthetic lead compounds from various plant and animal species as well as non-marine and marine microbes, as promising treatment modalities against cancer (4). These synthetic anti-cancer compounds are molecularly replicated to mimic the naturally-occurring compounds, with better properties, including more sustainable, cost effective, and with higher selectivity against cancer than normal cells (5). Some of the synthetic anticancer agents including sorafenib and methotrexate, act as tyrosine kinase inhibitors and antimetabolites, respectively, which are used in clinical practice (6). There is also new evidence indicating that antibiotics are effective not only in treating bacterial infections, but also in eradicating cancer stem cells without harming nor...
