Anti-Cancer Activity of a 5-Aminopyrazole Derivative Lead Compound (BC-7) and Potential Synergistic Cytotoxicity with Cisplatin against Human Cervical Cancer Cells

Abstract

The use of some very well-known chemotherapeutic agents, such as cisplatin, is limited by toxicity in normal tissues and the development of drug resistance. In order to address drug resistance and the side-effects of anti-cancer agents, recent research has focused on finding novel combinations of anti-cancer agents with non-overlapping mechanisms of action. The cytotoxic effect of the synthetic 5-aminopyrazole derivative N-[[3-(4-bromophenyl)-1H-pyrazol-5-yl]-carbamothioyl]-4-chloro-benzamide (BC-7) was evaluated by the bis-Benzamide H 33342 trihydrochloride/propidium iodide (Hoechst 33342/PI) dual staining method against HeLa, MeWo, HepG2, Vero, and MRHF cell lines. Quantitative fluorescence image analysis was used for the elucidation of mechanism of action and synergism with cisplatin in HeLa cells. BC-7 displayed selective cytotoxicity towards HeLa cells (IC50 65.58 ± 8.40 μM) and induced apoptosis in a mitochondrial- and caspase dependent manner. This was most likely preceded by cell cycle arrest in the early M phase and the onset of mitotic catastrophe. BC-7 increased the cytotoxic effect of cisplatin in a synergistic manner with combination index (CI) values less than 0.9 accompanied by highly favourable dose reduction indices. Therefore, the results obtained support the implication that BC-7 has potential anti-cancer properties and that combinations of BC-7 with cisplatin should be further investigated for potential clinical applications.

Inhibition of TMEM16A by Natural Product Silibinin: Potential Lead Compounds for Treatment of Lung Adenocarcinoma

“…The anticancer mechanism of silibinin was varied, including cell proliferation, invasion, and apoptosis. This work showed that silibinin was different from other anticancer drugs which were only cytotoxicity to cell death (Swanepoel et al, 2019). It also prevented the protein phosphorylation of MEK1/2 and ERK1/2 through inhibiting TMEM16A expression and finally arrested the cancer cells in G0/G1.…”

Cannabinoid Combination Induces Cytoplasmic Vacuolation in MCF-7 Breast Cancer Cells

“…Assays were conducted in 96-well plates and 9 sites per well were imaged, covering an area of approximately 63.5% of the total well area. The number of cells imaged was dependent on the cytotoxicity of the treatment [ 105 ].…”

Association of the Epithelial–Mesenchymal Transition (EMT) with Cisplatin Resistance

“…A very good example of its effectiveness has been shown when combined with Clarithromycin to suppress the invasion and proliferation of ovarian cancer cells, which elevates apoptotic cell death by increasing the production of reactive oxygen species (ROS) [43]. A combination of CP and a 5-aminopyrazole derivative lead compound (BC-7) stimulates M-phase arrest and prevents the proliferation of cervical cancer cells [44]. It is worth mentioning that CP and docetaxel (DOX) can be administered prior to surgery to increase the survival resection rate, reduce intraoperative blood loss, and extend the patient's survival time.…”