Lipophilic Grape Seed Proanthocyanidin Exerts Anti-Cervical Cancer Effects in HeLa Cells and a HeLa-Derived Xenograft Zebrafish Model

Lipophilic grape seed proanthocyanidin (LGSP) synthesized from GSP and lauric acid exhibits an excellent antioxidant and anti-inflammatory effect. However, its anti-cervical cancer activity is still unknown. In this study, the in vitro anti-cervical cancer activity of LGSP on HeLa cell lines was investigated by MTT assay, flow cytometry and Western blot analysis, and its effect was explored by a HeLa-derived xenograft zebrafish model. LGSP exhibited an excellent anti-proliferative effect on HeLa cells by increasing the level of reactive oxygen species, which further induced cell apoptosis and blocked cell cycle progression in the G2/M phase. LGSP-treated HeLa cells showed a reduction in mitochondrial membrane potential, upregulation of the Bax/Bcl-2 ratio, release of cytochrome c into the cytoplasm, and activation of cleaved caspase-9/3 and cleavage of PARP, thus indicating that LGSP induced apoptosis through the intrinsic mitochondrial/caspase-mediated pathway. In the zebrafish model, LGSP effectively suppressed the growth of a HeLa xenograft tumor. These data suggest that LGSP may be a good candidate for the prevention or treatment of cervical cancer.