Alizarin induces a multidirectional mechanism of anti-cancer action in cervical cancer and prostate cancer cells.

Abstract

Due to their multifaceted biological effects, anthraquinones have attracted increasing interest as potential anticancer agents. In this study alizarin has been analyzed for its activity against cervical and prostate cancer cell models, which represent malignancies with a high global disease burden. The effects of alizarin were studied in HeLa and DU145 cell lines using both two- and three-dimensional culture systems. Morphological and ultrastructural analyses revealed changes characteristic of apoptosis, accompanied by increased caspase-3/7 activity, phosphorylation of the antiapoptotic protein Bcl-2, activation of ATM and H2A.X in response to DNA damage, inhibition of the PI3K/MAPK signaling pathway, and alterations in mitochondrial morphology associated with elevated reactive oxygen species generation. Alizarin also induced features consistent with mitotic catastrophe and modulated autophagy-related processes. A synergistic proapoptotic effect was observed when alizarin was combined with Venetoclax, a selective Bcl-2 inhibitor, resulting in enhanced cytotoxicity in both cervical and prostate cancer cell models. The antiproliferative effects of alizarin were further associated with inhibition of cell migration, reduction of the mitotic index, and alterations in cell cycle progression, including accumulation of cells in the G2/M phase. Comparable cytotoxic effects were also observed in three-dimensional spheroid cultures. Overall, these findings indicate that alizarin affects multiple cellular pathways involved in cancer cell survival and proliferation and may be of interest in the context of combination anticancer strategies, although further studies are required to clarify the underlying molecular mechanisms.