Apple procyanidins induce tumor cell apoptosis through mitochondrial pathway activation of caspase-3
Tomisato Miura1, Mitsuru Chiba, Kosuke Kasai
1Department of Pathologic analysis, Hirosaki University Graduate School of Health Sciences, 66-1, Hon-cho, Hirosaki, Aomori 036-8564, Japan. tomisato@cc.hirosaki-u.ac.jp
Abstract:
Various epidemiologic and experimental in vivo and in vitro studies have suggested that polyphenols derived from fruits, vegetables and beverages might decrease the risk of developing lifestyle diseases, such as cardiovascular disorders and cancer. Apples are a major dietary source of polyphenols. Here we investigated the antitumor activity of apple polyphenols (APs) and procyanidins, namely condensed tannins, both in vitro and in vivo studies. APs and procyanidins inhibited the growth of transplanted B16 mouse melanoma cells and BALB-MC.E12 mouse mammary tumor cells, and increased the survival rate of the host mice-transplanted B16 cells. Among the APs, the apple procyanidins specifically, rather than other polyphenols such as chlorogenic acid, (-)-epicatechin, phloridzin and procyanidin B2, had a major effect on cell proliferation and induced apoptosis in vitro. The apple procyanidins increased mitochondrial membrane permeability and cytochrome c release from mitochondria and activated caspase-3 and caspase-9 within the tumor cells. In addition, we separated eight procyanidin fractions according to the degree of polymerization using normal-phase chromatography, and detected strong anti-tumor activity in the procyanidin pentamer and higher degree fractions. Our results indicate that the oral administration of apple procyanidins inhibits the proliferation of tumor cells by inducing apoptosis through the intrinsic mitochondrial pathway.
Insights
Apple procyanidins, a type of polyphenol, show significant antitumor activity. These compounds inhibit tumor cell growth and promote apoptosis, offering potential for cancer prevention and treatment strategies.
Area of Science:
- Nutritional Biochemistry
- Cancer Research
- Pharmacology
Background:
- Polyphenols from fruits and vegetables are linked to reduced risk of lifestyle diseases like cancer.
- Apples are a rich dietary source of polyphenols, including procyanidins.
Purpose of the Study:
- To investigate the antitumor activity of apple polyphenols (APs) and procyanidins.
- To determine the specific mechanisms by which apple procyanidins exert their anti-cancer effects.
Main Methods:
- In vitro and in vivo studies using B16 mouse melanoma and BALB-MC.E12 mouse mammary tumor cells.
- Separation of procyanidin fractions based on polymerization degree.
- Analysis of apoptosis-related markers, including mitochondrial membrane permeability and caspase activation.
Main Results:
- Apple procyanidins, but not other tested polyphenols, significantly inhibited tumor cell proliferation and induced apoptosis in vitro.
- Oral administration of apple procyanidins increased survival rates in tumor-bearing mice.
- Higher degree procyanidin fractions (pentamer and above) exhibited potent anti-tumor activity.
- Procyanidins induced apoptosis via the intrinsic mitochondrial pathway, involving cytochrome c release and caspase-3/9 activation.
Conclusions:
- Apple procyanidins possess significant antitumor properties.
- The anti-proliferative and pro-apoptotic effects are mediated through the mitochondrial pathway.
- Apple procyanidins, particularly higher polymers, represent a promising natural compound for cancer prevention and therapy.
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