Cytotoxic Effects of Novel Pyrazole Derivatives (BK-35 & HEXUR-1) on MDA-MB-231 Breast Cancer Cells

Ahmad Baijuri, Nur Hanis Adni (2021) Cytotoxic Effects of Novel Pyrazole Derivatives (BK-35 & HEXUR-1) on MDA-MB-231 Breast Cancer Cells. [Project Paper] (Submitted)

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Abstract

Breast cancer is the most frequently diagnosed neoplasm and the leading cause of cancer death among females worldwide. According to LOBOCAN 2020, breast cancer has caused 684 996 deaths in 2020, ranking as the fifth leading cause of cancer mortality, and about 2 261 419 females were iagnosed with breast cancer making it the most common cancer in the world. Extensive efforts have been made in finding and developing new therapies to treat patients with breast cancer. However, patients undergoing treatment particularly chemotherapy often presenting some adverse side effects. Therefore, the development of new anticancer drugs with less side effects are needed to treat patients with breast cancer. Novel pyrazole molecules containing fivemembered heterocyclic chains has been reported to possess anticancer properties. The current study investigates the effects of two novel pyrazole derivatives (BK-35 and HEXUR-1) on the MDA-MB-231 breast cancer cell line. Objectives: This study aims to determine the cytotoxic effects and the morphology of MDA-MB-231 cells treated with BK-35 and HEXUR-1 by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and inverted microscope, respectively. Methodology: MDA-MB- 231 cells were grown in a complete growth media which consisted of Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% of Fetal Bovine Serum (FBS) together with 1% Penicillin-Streptomycin and cells were cultured at 37ºC in a humidified incubator with 5% CO2. The cytotoxic effects of BK-35 and HEXUR-1 were then determined using MTT assay at three different incubation time which were at 24-, 48- and 72-hours. The morphological changes of MDA-MB-231 cells were observed at each concentration and incubation time point. Results: From MTT assay, the IC50 values of BK-35 for MDA-MB-321 cells at 48- and 72-hours were 184μM and 130μM, respectively. No cytotoxic effect shown after 24-hours incubation period with IC50 more than 200μM for BK-35. The IC50 values of HEXUR-1 for MDA-MB-231 cells ranging from 58 to 116μM at 24-,48- and 72-hour time points. The morphological characteristics of apoptosis such as nuclear fragmentation, membrane blebbing, cell shrinkage and also apoptotic bodies were seen in MDA-MB-231 cells treated with BK-35 and HEXUR-1. Discussion: Both novel pyrazole derivatives were shown to be cytotoxic towards the MDA-MB-231 cells as the cells reduced throughout the incubation period. Morphological characteristics of apoptosis such as cell shrinkage, membrane blebbing, nuclear fragmentation, and apoptotic bodies were noticed, implying that the mode of cell death induced by BK-35 and HEXUR-1 on MDA-MB-231 cells could be due to apoptosis. Conclusion: Both novel pyrazole derivatives, BK-35 and HEXUR-1 have demonstrated cytotoxic effects against MDA-MB-231 breast cancer cells. This suggests that these two pyrazole derivatives can potentially be developed as novel anticancer drug candidates for the treatment of breast cancer.

Item Type:	Project Paper
Faculty:	Faculty of Medicine and Health Science
Depositing User:	Ms. Nor Safa'aton Saidin
Date Deposited:	22 Aug 2023 07:10
Last Modified:	22 Aug 2023 07:10
URI:	http://psaspb.upm.edu.my/id/eprint/1008

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