Liposomal vitamin C as a modulator of the efficacy of ceralasertib therapy in ovarian cancer.

Liposomal Vitamin C as a Modulator of the Efficacy of Ceralasertib Therapy in Ovarian Cancer.

Patrycja Gralewska-Zając, Aleksandra Przybylska, Marek Langner, Magdalena Przybyło, Agnieszka Marczak, Aneta Rogalska

Int J Mol Sci

Mar 13, 2026

Sources

0:00 / 0:00

Sign in to access this feature

Create a free account or sign in to use AI summaries, listen to articles, download PDFs, and save to your library.

203 views

Abstract

Clinical evidence suggests that vitamin C (VitC) may enhance the efficacy of cancer chemotherapy. However, its high oxidating and reducing activity results in low stability in physiological fluids, which may compromise its supportive role in cancer therapies. VitC stability improves when located in a region where water activity is reduced and exposure to a limited amount of ferrous ions. This can be achieved when VitC is encapsulated in liposomes. Here, we present a novel combinatorial effect of a liposomal formulation of vitamin C (LVC, liposomal VitC) and an ataxia-telangiectasia and Rad3-related (ATR) kinase inhibitor (ATRi, ceralasertib) on cancer cells. The cytotoxic effects of vitamin C, LVC and ATRi were evaluated using spectrophotometric and spectrofluorimetric assays, flow cytometry and Western blot. Lipid peroxidation was assessed via fluorescence microscopy and quantified by spectrofluorimetric assays. DNA damage was examined by Western blot. The combination has higher efficacy than ceralasertib alone in genetically diverse ovarian cancer cell lines. LVC offers protective effects when used as an adjuvant during anticancer therapy. We found that the inhibition of the ATR pathway in the presence of LVC results in increased intracellular calcium levels, elevated lipid peroxidation, and higher Feconcentrations. The upregulation of ROS, together with the increased expression of long-chain-fatty-acid-CoA ligase 4 (ACSL4) following co-treatment with ATRi and LVC, indicates the activation of ferroptotic pathways. The formation of DNA double-strand breaks suggests replication fork collapse. Our findings demonstrates that this synthetic targeted therapy, combining a novel liposomal formulation of VitC with an ATR inhibitor, not only enhances DNA damage and the cytotoxic efficacy of ceralasertib but also effectively drives ovarian cancer cells toward cell death.