Abstract
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.
Highlights
Cervical cancer is the fourth most common cancer in women with approximately570,000 new cases and 311,000 deaths reported worldwide in 2018 [1]
The IC50 values of Lipophilic grape seed proanthocyanidin (LGSP) and Grape seed proanthocyanidin (GSP) for anti-proliferative effect on HeLa cells were 57.97 ± 1.23 and 111.16 ± 1.02 μg/mL, respectively, after 48 h of treatment, indicating that LGSP had stronger anti-cervical cancer activity compared to GSP
The cytochrome c released from the mitochondria activated the caspase apoptosis pathway, and we explored whether LGSP activated it
Summary
Cervical cancer is the fourth most common cancer in women with approximately570,000 new cases and 311,000 deaths reported worldwide in 2018 [1]. Significant progress has been made in the treatment of cervical cancer, they are costly and unbearable. A large number of epidemiologic studies have investigated the relation between dietary polyphenols and cancer [3], and these have demonstrated that phenolic compounds can reduce the risk of chronic diseases, including cancer, diabetes, cardiovascular and neurodegenerative diseases [4,5]. Phenolic compounds, which are widely distributed in food, are regarded as an important source of antioxidants in the daily diet. Grape seed proanthocyanidin (GSP), the major polyphenol component in grape seed, has been widely used as a dietary supplement and food additive due to its various biological activities [6]: antioxidant [7], anti-tumor [8], anti-inflammatory [9] and anti-cardiovascular disease [10]. The hydrophilicity of GSP with its low solubility in lipid systems limits its application in lipidic food matrices and hinders its bioactivity [11]
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