A Comparative Study of the Anticancer Activity and PARP-1 Inhibiting Effect of Benzofuran–Pyrazole Scaffold and Its Nano-Sized Particles in Human Breast Cancer Cells

Abstract

Breast cancer is considered the most common and deadly cancer among women worldwide. Nanomedicine has become extremely attractive in the field of cancer treatment. Due to the high surface to volume ratio and other unique properties, nanomaterials can be specifically targeted to certain cells and tissues to interact with the living systems. The strategic planning of this study is based on using the nanoprecipitation method to prepare nanoparticles BZP-NPs (3.8–5.7 nm) of the previously prepared benzofuran–pyrazole compound (IV) BZP which showed promising cytotoxic activity. The capacity of BZP and BZP-NPs to suppress the growth of human breast tumor MCF-7 and MDA-MB-231 cells was evaluated using MTT assay. The IC50 doses of BZP and BZP-NPs targeting normal breast cells MCF-12A exceeded those targeting the cancer cells by >1000-fold, demonstrating their reasonable safety profiles in normal cells. Furthermore, cell cycle analysis, apoptosis induction detection, assessment of p53, Bcl-2, caspase-3, and PARP-1 levels of BZP and its nano-sized-BZP-NPs particles were also evaluated. Although the obtained results were in the favor of compound IV in its normal-sized particles, BZP-NPs appeared as a hit compound which showed improved cytotoxicity against the tested human breast cancer cells associated with the induction of pre-G1 apoptosis as well as cell cycle arrest at G2/M phase. The increase in caspase-3 level, upregulation of p53, and downregulation of Bcl-2 protein expression levels confirmed apoptosis. Furthermore, ELISA results exhibited that BZP-NPs produced a more favorable impact as a PARP-1 enzyme inhibitor than the parent BZP.

RETRACTED: Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells

“…Therefore, augmentation of cytotoxicity by formulating ICA into phytosomes is further supported by these data. Enhancement of caspase-3 by nanostructured formulations has been previously reported [37,57,58]. In addition, caspase-3 results are consistent in that the observed MMP disturbances that initiate caspase-3 activation promote typical apoptotic features.…”

“…Thus, pre-G1 apoptosis and cell cycle arrest at the G2-M phase could explain the enhanced cytotoxic effect of ICA-phytosome. This is supported by other observations on nanoparticles [37]. Encapsulation of silver nanoparticles in lipids has been reported to enhance apoptosis [54].…”

“…Therefore, it is considered an excellent marker of apoptosis. [37]. Therefore, augmentation of cytotoxicity by formulating ICA into phytosomes is further supported by these data.…”

“…Cell cycle analysis was studied by flow cytometry experiments following reported methods [37,38]. The cells were incubated with the samples: ICA-phytosomes, pure drug, and placebo-phytosomes.…”

RETRACTED: Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells

“…The cell cycle analysis was carried out using flow cytometry experiments following previously-described methods [ 24 , 25 ]. The cells were incubated for 24 h with 2.1 µM of the optimized TQ-loaded phytosomes, free-TQ, and blank phytosomes.…”