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

• Main Authors: Manal M. Anwar, Somaia S. Abd El-Karim, Ahlam H. Mahmoud, Abd El-Galil E. Amr, Mohamed A. Al-Omar
• Format: Article
• Language: English
• Published: MDPI AG 2019-06-01
• Series: Molecules
• Subjects: breast cancer; benzofuran–pyrazole; nanoparticles; cytotoxic activity; apoptosis; PARP-1 inhibition
• Online Access: https://www.mdpi.com/1420-3049/24/13/2413

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 <b>BZP-NPs</b> (3.8–5.7 nm) of the previously prepared benzofuran–pyrazole compound (<b>IV</b>) <b>BZP</b> which showed promising cytotoxic activity. The capacity of <b>BZP</b> and <b>BZP-NPs</b> to suppress the growth of human breast tumor MCF-7 and MDA-MB-231 cells was evaluated using MTT assay. The IC₅₀ doses of <b>BZP</b> and <b>BZP-NPs</b> targeting normal breast cells MCF-12A exceeded those targeting the cancer cells by &gt;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 <b>BZP</b> and its nano-sized-<b>BZP-NPs</b> particles were also evaluated. Although the obtained results were in the favor of compound <b>IV</b> in its normal-sized particles, <b>BZP-NPs</b> 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 <b>BZP-NPs</b> produced a more favorable impact as a PARP-1 enzyme inhibitor than the parent <b>BZP</b>.