Growth Inhibition of Two Prenylated Chalcones on Prostate Cancer Cells through the Regulation of the Biological Activity and Protein Translation of Bloom Helicase

Abstract

Bloom (BLM) helicase is an important member of the RecQ family of DNA helicases that plays a vital role in the maintenance of genomic stability. The defect of BLM helicase leads to a human genetic disorder called Bloom syndrome, characterized by genomic instability, specific phenotypic features, and a predisposition to many types of cancer. The predisposition to cancer caused by BLM helicase is due to defects in important DNA metabolic pathways such as replication, recombination, and repair. Therefore, the aim of this work was to investigate the effects of two prenylated chalcones, WZH-10 and WZH-43, on the expression of BLM helicase in prostate cancer cells, as well as the biological activity of the purified BLM helicase from cancer cells. This might lead to a better understanding of the role of BLM helicase in the aforementioned DNA metabolic pathways that directly influence chromosomal integrity leading to cancer. The results indicated that the two prenylated chalcones inhibited the growth of prostate cancer cells PC3 by inducing apoptosis and arresting the cell cycle. However, they only inhibited the protein expression of BLM helicase without regulating its transcriptional expression. In addition, they did not significantly regulate the expression of the homologous family members WRN and RECQL1, although the DNA unwinding and ATPase activity of BLM helicase were inhibited by the two prenylated chalcones. Finally, a negligible effect was found on the DNA-binding activity of this enzyme. These results demonstrated that prenylated chalcones can be an effective intervention on the expression and function of the BLM helicase protein in cancer cells to inhibit their growth. Therefore, they might provide a novel strategy for developing new anti-cancer drugs targeting the genomic stability and DNA helicase.