Proanthocyanidin from grape seeds inactivates the PI3-kinase/PKB pathway and induces apoptosis in a colon cancer cell line

Engelbrecht, Anna‐Mart; Mattheyse, Mary; Ellis, Beverly; Loos, Ben; Thomas, Mark; Smith, Rob; Peters, Susanna; Smith, Carine; Myburgh, Kathryn H.

doi:10.1016/j.canlet.2007.08.020

Cited by 128 publications

(106 citation statements)

References 41 publications

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“…PAC-1 treatment lead to degradation of DNA repair factor PARP, the loss of ΔΨ m which is an indicator of irreversible apoptotic responses of drug-treated cells (39) and inactivation of pro-survival factor AKT. Similarly, B-type PACs from grape seeds have been shown to suppress Pi3K/ AKT signaling in skin and colon cancer cells (40,41). This pathway is particularly important in the drug response of tumor cells, such as ovarian cancer, that display activation of AKT and other components or low expression of tumor suppressors (e.g.…”

Section: Discussionmentioning

confidence: 99%

Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells

Kim

Singh²,

Singh³

et al. 2011

Int J Oncol

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Abstract. Cranberry extracts may provide beneficial health effects in the treatment of various diseases, including cancer. However, the underlying molecular mechanisms of antineoplastic properties are not understood. We report the effect of a proanthocyanidin (PAC)-rich isolate from cranberry (PAC-1) as a therapeutic agent with dual activity to target both ovarian cancer viability and angiogenesis in vitro. PAC-1 treatment of chemotherapy-resistant SKOV-3 cells blocked cell cycle progression through the G 2 /M phase, increased the generation of reactive oxygen species (ROS), and induced apoptosis through activation of intrinsic and extrinsic pathway components. Cytotoxicity of PAC-1 was partially based on ROS generation and could be blocked by co-treatment with antioxidant glutathione. PAC-1 reduced the cell viability of both SKOV-3 ovarian cancer cells and HUVEC endothelial cells in a dose-dependent manner and blocked the activation of the pro-survival factor AKT. Furthermore, PAC-1 blocked vascular endothelial growth factor (VEGF)-stimulated receptor phosphorylation in endothelial cells, which correlated with the inhibition of endothelial tube formation in vitro. Our findings suggest that PAC-1 exerts potent anticancer and anti-angiogenic properties and that highly purified PAC from cranberry can be further developed to treat ovarian cancer in combinational or single-agent therapy.

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Section: Discussionmentioning

confidence: 99%

Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells

Kim

Singh²,

Singh³

et al. 2011

Int J Oncol

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“…Recent interest in the natural plant components proanthocyanidins has been stimulated by their potential protective effects on normal cells and apoptosis-inducing effects on cancer cells (28,29). Until now, several kinds of proanthocyanidins, abundantly available in various parts of plants, such as seeds, fruits, bark, and berries, have been extracted from wide variety of plants such as grape, cocoa, apple, pine, sorghum, blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry, each of which has been claimed to exert anticarcinogenic activity in cellular models of cancer.…”

Section: Discussionmentioning

confidence: 99%

Pinus massoniana bark extract selectively induces apoptosis in human hepatoma cells, possibly through caspase-dependent pathways

Liu²,

Feng³

et al. 2010

Int J Mol Med

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Abstract. Pinus massoniana bark extract (PMBE) is a mixture of flavonoids, whose antioxidant and apoptosisinducing properties have been confirmed in vitro. In this study, the apoptotic effect and mechanism of PMBE in HepG2 human hepatoma cells were evaluated. PMBE exerted dose-and time-dependent cell growth inhibition on HepG2 cells, and selectively induced apoptosis without impact on normal liver L-02 cells. Apoptosis induced by PMBE in HepG2 cells was also confirmed by annexin-V/PI staining, transmission electron microscopy and sub-G1 phase accumulation. Moreover, PMBE also slightly blocked the cell cycle in the G2/M and S phases in HepG2 cells. The investigation of the mechanism by which PMBE induced apoptosis in HepG2 cells indicated that activation of extrinsic and intrinsic caspase, inhibition of NF-κB activation and decrease of the antiapoptotic protein Bcl-2 and the intact Bid protein were involved. Furthermore, the antitumor activity of PBME was demonstrated in vivo by a 42.88-69.94% reduction rate of tumor weight in H22 tumor-implanted mice. Taken together, these data indicate that PMBE selectively induces apoptosis in HepG2 cells through caspase-dependent pathways, and inhibits tumor growth in vivo, making it a potential candidate for anticancer therapeutics.

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“…GSP is of a diphenylpropane structure of C 6 -C 3 -C 6 . Most often found as a glycoside derivative, this compound class is composed of three monomer units of catechin, epicatechin, and epigallocatechin (Harborne and Mabry., 1982) GSP can clear off free radicals, protect the over-oxidative damage and prevent a range of diseases caused by free radicals, such as myocardial infarction, atherosclerosis, drug-induced liver and kidney injury more, it has functions of anti-thrombotic, anti-tumor, antimutagenic, anti-radiation, and anti-fatigue (Engelbrecht et al, 2007). GSP has been shown to inhibit lipid peroxidation, platelet aggregation, capillary permeability and fragility and to affect enzyme systems, including phospholipase A 2 , cyclooxygenase and lipooxygenase (Robert et al, 1990).…”

Section: +mentioning

confidence: 99%

Ameliorative effects of grape seed proanthocyanidins on cadmium induced metabolic alterations in rats

Bashir

Manoharan

Prabu

2014

International Journal of Biological Research

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Objective: To study the ameliorative effects of grape seed proanthocyanidins (GSP) against cadmium (Cd) induced hyperglycemia, hypercholesterolemia and hyperlipidemia in rats. Methods: Wistar rats, body weight 180-200g, were randomly divided into four groups, six rats in each group. First group (control) represented the control animal, the second group (Cd) was fed orally with Cd in the form of CdCl 2 (5mg/kg bw), the third group (GSP) was fed with GSP (200 mg/kg bw) and to the fourth group (Cd+GSP), CdCl 2 was administered orally at a dose of (5 mg/kg bw) and pretreated with GSP (200 mg/kg bw) 90 min before Cd intoxication for 4 weeks. At the end of experiment, rats were sacrificed; blood and liver samples were collected and used for analysis of various metabolic parameters. Results: The result of the present study revealed that Cd exposure caused significant reduction in food intake and body weight gain, but increased the liver weight. GSP administration significantly revert all these changes to normal level. Cd intoxication induced hyperglycemia, elevate plasma glucose and lipid profiles and decline in high density lipoprotein (HDL) -cholesterol respectively. The GSP pretreatment regimen was beneficial in the restoration of the increased serum levels of TC, TG and lipid profiles and of the suppressed insulin and total antioxidants on Cd exposure. Conclusion: From the present investigation, it may be concluded that Cd intoxication caused deleterious effects on the metabolism of rats which were successfully restored by GSP. Therefore, the present work suggests that GSP is a feasible therapeutic agent to improve and treat patients with hyperlipidemia, obesity, hyperglycemia in addition to its anti-oxidant properties and can be used as a component in food to promote the health of people.

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Proanthocyanidin from grape seeds inactivates the PI3-kinase/PKB pathway and induces apoptosis in a colon cancer cell line

Cited by 128 publications

References 41 publications

Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells

Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells

Pinus massoniana bark extract selectively induces apoptosis in human hepatoma cells, possibly through caspase-dependent pathways

Ameliorative effects of grape seed proanthocyanidins on cadmium induced metabolic alterations in rats

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