Effect of procyanidin-rich extract from natural cocoa powder on cellular viability, cell cycle progression, and chemoresistance in human epithelial ovarian carcinoma cell lines

Abstract

Background:Over the last 400 years, cocoa and chocolate have been described as having potential medicinal value, being consumed as a beverage or eaten as food. Concentration–dependant, antiproliferation, and cytotoxic effects of some of their polyphenolic constituents have been demonstrated against various cancers. Such an effect remains to be demonstrated in ovarian cancerObjective:To investigate the effect of cocoa procyanidins against ovarian cancer in vitro using OAW42 and OVCAR3 cell lines.Materials and Methods:Cocoa procyanidins were extracted and enriched from non alkalized cocoa powder. The polyphenolic content and antioxidant activity were determined. Effect on cell viability was determined after the treatment with ≤1000 μg/mL cocoa procyanidin-rich extract on OAW42 and OVCAR3 and normal human dermal fibroblasts. Similarly, chemosensitization effect was determined by pretreating cancer cell lines with extract followed by doxorubicin hydrochloride treatment. The effect of treatment on cell cycle and P-glycoprotein (P-gp) expression was determined using flow cytometry.Results:The cocoa extract showed high polyphenolic content and antioxidant activity. Treatment with extract caused cytotoxicity and chemosensitization in OAW42 and OVCAR3 cell lines. Normal dermal fibroblasts showed an increase in cell viability post treatment with extract. Treatment with extract affected the cell cycle and an increasing percentage of cells in hypodiploid sub-G1/G0 phase was observed. Treatment of OVCAR3 with the extract caused reduction of P-gp expression.Conclusion:Cocoa procyanidins were found to be selectively cytotoxic against epithelial ovarian cancer, interfered with the normal cell cycle and sensitized cells to subsequent chemotherapeutic treatment. Chemosensitization was found to be associated with P-gp reduction in OVCAR3 cells.SUMMARY Among the naturally occurring flavonoids, procyanidins have been shown to be effective against cancersNon alkalized cocoa powder is one of the richest sources of procyanidinsCocoa procyanidin-rich extract (CPRE) caused cytotoxicity and chemosensitization in ovarian carcinoma cell lines OAW42 and OVCAR3CPRE affected normal cell cycle progressionCPRE also downregulated P-glycoprotein, which mediates chemoresistance in multidrug-resistant OVCAR3 cell line. Abbreviations used: P-gp: P-glycoprotein, CPRE: Cocoa procyanidin rich extract, DMAC: 4-dimethylaminocinnamaldehyde, DPPH: Diphenylpicrylhydrazyl, ABTS: 2,2’;-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid), PI: Propidium iodide, FITC: Fluorescein isothiocyanate, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, TLC: Thin layer chromatography, HPTLC: High-performance thin layer chromatography.

A Chitosan-PLGA based catechin hydrate nanoparticles used in targeting of lungs and cancer treatment

“…Polyphenol structure is characterized by the presence of multiphenol units, which might contribute to oxidative stability of plant tissue and other organoleptic characteristics, such as color, flavor, and odor ( Pandey and Rizvi, 2009 ). Due to favorable safety profile and profound antioxidant activity, polyphenolic phytochemicals have been intensively studied as anticancer adjuvants ( Lai et al, 2017 , Akowuah et al, 2009 , Taparia and Khanna, 2016 ). Particularly, in mice‑harboring mammary carcinoma 4T1, green tea polyphenols dramatically suppressed cancer development and inhibited tumor metastasis ( Baliga et al, 2005 ).…”

Cancer Chemopreventive Potential of Procyanidin

“…Procyanidin treatment increased the G1 cell population in BxPC-3 ( 45 ), OVCAR ( 46 ), oral squamous cell carcinoma 25 (SCC-25) ( 11 ), and Caco-2 cells ( 23 ), which is demonstrative of its apoptotic effects. Earlier studies suggest that the procyanidin-induced arrest of the cell cycle might be mediated by the induction of p21 expression ( 19 , 47 ).…”

“…Taparia et al . ( 46 ) reported that procyanidin is cytotoxic to QAW42 and OVCAR3 epithelial ovarian cancer cells via several mechanisms, inducing apoptosis with DNA damage and caspase-3 mediation. Downregulation of pro-MMP-2 and reduction in active MMP-2 levels imply a decreased invasive potential of the cells ( 51 ).…”

“…Procyanidin is cytotoxic to ovarian cancer cells, OAW42 and OVCAR3 cells, and sensitizes them to doxorubicin. Chemosensitization was accompanied with decreased P-gp levels, and an increased cell population in the hypodiploid sub-G0 phase after treatment with procyanidin ( 46 ). Regarding the approaches to overcome chemo-resistance conferred by P-gp, Zhao et al .…”

Anti-cancer effects of polyphenolic compounds in epidermal growth factor receptor tyrosine kinase inhibitor-resistant non-small cell lung cancer

“…[ 6 ] Due to favorable safety profile and profound antioxidant activity, polyphenolic phytochemicals have been intensively studied as anticancer adjuvants. [ 8 9 10 ] Particularly, in mice-harboring mammary carcinoma 4T1, green tea polyphenols dramatically suppressed cancer development and inhibited tumor metastasis. [ 11 ] Furthermore, a clinical study on patients with intestinal premalignant lesions showed that 6-month treatment of quercetin and curcumin inhibited the development of polyps both in number and size.…”