Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468

Ashourpour, Maryam; Mostafavi Hosseini, Fatemeh; Amini, Mohsen; Saeedian Moghadam, Ebrahim; Kazerouni, Faranak; Arman, Seyed Yousef; Shahsavari, Zahra

doi:10.31557/APJCP.2021.22.7.2079

Pyrazole Derivatives Induce Apoptosis via ROS Generation in the Triple Negative Breast Cancer Cells, MDA-MB-468

Document Type : Research Articles

Authors

¹ Department of Laboratory Medicine, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

² Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran.

³ School of Chemistry, Australian Centre for Nano Medicine and the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of New South Wales, Kensington, New South Wales, Australia.

⁴ Department of Clinical Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

10.31557/APJCP.2021.22.7.2079

Abstract

Background: Triple-negative breast cancer accounts for approximately 15–20% of all breast carcinomas and is associated with earlier age of onset, aggressive clinical course, and dismal prognosis. A series of 1,3-diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1 H-Pyrazole and 1,3-diaryl-5- (3,4,5-trimethoxyphenyl)- 1 H-Pyrazole were evaluated for their anticancer activity against MDA-MB-468, human triple negative breast cancer cell line. Methods: The cytotoxic effects of Pyrazole derivatives on the growth of MDA-MB-468 and AGO1522 were determined using MTT assay. Annexin-V-FITC and PI staining were performed to detect apoptosis and cell cycle distribution using Flow cytometry. The level of Reactive oxygen species (ROS) formation and caspase 3 activity were determined accordingly. Results: Pyrazole derivatives induced a dose and time-dependent cell toxicity in MDA-MB-468 compared with untreated cells. The results showed that 3-(4-methoxyphenyl)-1-(p-tolyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-Pyrazole (3f) was the most active compound with IC50 values 14.97 μM and 6.45 μM compared with Paclitaxel with IC50 values 49.90 μM and 25.19 μM, after 24 and 48 hours, respectively. Upon treatment with 14.97 μM of 3f after 24 h, the compound induced cell cycle arrest in S phase. 3f provoked apoptosis was accompanied by the elevated level of ROS and increased caspase 3 activity in MDA-MB-468 cells compared with untreated cells. Conclusion: The overall results of the present study provided evidence for the cytotoxicity of compound 3f against MDA-MB-468 cells in comparison to reference standard, Paclitaxel. It proves that compound 3f can trigger apoptosis through ROS production and caspase 3 activation. These bring supportive data for future investigations that will lead to their use in cancer therapy.

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