The current study was designed to evaluate the affect of the flavonoid phloretin's antitumor activity when combined with paclitaxel for treatment of human Hep G2 liver cancer cells. Phloretin, which is a component of apples, apple juice, and apple cider, is known to inhibit type II glucose transporter. In the study, liver cancer cells were first shown to have elevated expression (greater than five-fold) of type II glucose transporter mRNA compared to nonmalignant hepatocytes. In vitro and in vivo experiments were then performed to assess phloretin's antitumor activity when combined with paclitaxel. Phloretin's inhibition of type II glucose transporter was found to potentiate the anticancer effects of paclitaxel, resensitizing Hep G2 liver cancer cells to the drug. Further analysis demonstrated that caspases 3, 8, and 9 were involved in the apoptosis. A SCID mouse model was used to evaluate the antitumor therapeutic efficacy of phloretin (10 mg/kg body weight) plus paclitaxel (1 mg/kg body weight) compared to paclitaxel alone. Hep G2-xenografted tumor volume in the mice was found to be reduced more than fivefold in the phloretin plus paclitaxel-treated mice compared to the group treated with paclitaxel alone. The authors conclude that phloretin may be useful for cancer chemotherapy and chemoprevention.

Rats were given the whole apple extracts starting 2 weeks prior to the administration of a substance which normally causes such rats to develop mammary tumors. The apple extracts inhibited the formation of mammary tumors and this effect was dose-dependent.

Apples are a major dietary source of polyphenols. Apple extracts were shown to inhibit hormone receptor positive breast cancer cell growth in vitro using both estrogen-dependent and estrogen-independent human breast cancer cell lines. Cyclin D1 and Cdk4 proteins decreased in a dose-dependent manner after exposure to apple extracts. The study authors conclude that the antiproliferative activities of apple extracts toward human breast cancer cells might be due to the modulation effects of apple phytochemicals on cell cycle machinery.

Apple polyphenols and procyanidins were found to inhibit the growth of mouse mammary tumor cells in vitro and in vivo. The oral administration of apple procyanidins was found to have an antiproliferative effect on tumor cells by causing apoptosis.

Thirteen triterpenoids isolated from apple peels were evaluated. Most were found to have potent antiproliferative activity against hormone receptor positive human breast cancer cells. The authors conclude that triterpenoids may be partially responsible for the anticancer properties of whole apples.

Nuclear factor κB (NF-κB) is a transcription factor that plays a significant role in cell inflammation, proliferation, and apoptosis. In cancer cells, NF-κB facilitates resistance to chemotherapy by promoting cell proliferation and inhibiting apoptosis. The study examined the effects of selected phytochemicals and apple extracts on NF-κB activation in hormone receptor positive human breast cancer cells. Apple extracts and curcumin both were found to inhibit NF-κB activation of breast cancer cells.

The authors analyzed data from studies of various cancers conducted in Italy during the period 1991 to 2002. The studies included 2569 breast cancer cases. The results were adjusted for age, study center, education, body mass index, tobacco smoking, alcohol drinking, total energy intake, vegetable consumption and physical activity. There was found to be a consistent inverse relationship between the consumption of apples and the risk of breast cancer.

Food frequency questionnaires were given to 90,630 women in the Nurses Health Study II in 1991 and 1995 to evaluate the association of flavonol intake with breast cancer risk in premenopausal women who were between 26 and 46 years at baseline in 1991. During eight years of follow-up, there were 710 cases of invasive breast cancer. There were no associations seen between consumption of individual flavonols such as kaempferol, quercetin or myricetin and breast cancer risk. The multivariate RR, comparing highest to lowest quintiles of cumulative average flavonol intake, was 0.94 for sum of flavonol-rich foods. Among the major food sources of flavonols, the authors found a significant inverse association of breast cancer with intake of beans and lentils but not with tea, onions, apples, string beans, broccoli, green pepper or blueberries.

Total and individual polyphenolics differed significantly among eight apple cultivars tested, and the peels had higher concentrations than the fleshes. Red Delicious and Northern Spy had the highest concentrations and Empire the lowest. Sixteen distinct polyphenolic compounds were found, of which some were found almost exclusively in the peel.