Inhibitory Effects of Combination of Lycopene and Genistein on 7,12- Dimethyl Benz(a)anthracene-Induced Breast Cancer in Rats

Abstract

Breast cancer is one of the most common cancers in women. Carotenoids and soy isoflavones have been postulated to have breast cancer preventive effects. We investigated the potential preventive effects of lycopene and genistein, alone and in combination, on breast cancer development in female Wistar rats treated with 7,12-dimethylbenz[a]anthracene (DMBA), a carcinogen known to induce breast tumors. Mammary carcinogenesis was initiated by a single, oral gavage of DMBA (80 mg/kg body weight) at 55 days of animal age. Fifty female Wistar rats were divided into 5 experimental groups having 10 animals per group: Group 1 (normal control), Group 2 (DMBA control), Group 3 (DMBA + lycopene), Group 4 (DMBA + genistein), and Group 5 (DMBA + lycopene and genistein). Rats were fed either lycopene (20 mg /kg bw) or genistein (2 mg /kg bw) by oral gavage (3 times per week) starting 2 wk prior to DMBA injection. Treatment was continued for 20 wk. Rats treated with DMBA developed mammary tumors with 100% tumor incidence during the 20-wk study. Inhibition of mammary cancer incidence by lycopene (70%), genistein (60%) and their combination (40%) was observed. Tumor weight decreased by 48%, 61%, and 67%, and mean tumor volume decreased by 18%, 35%, and 65% with lycopene, genistein, and lycopene + genistein, respectively (P < 0.01 for the combination). The proportions of adenocarcinoma masses decreased with lycopene and genistein combination (P < 0.05). Administration of lycopene and genistein combination suppressed breast cancer development and was associated with a decrease in MDA, 8-isoprostane, and 8-OhdG levels and with an increase in serum lycopene and genistein levels. Animals administered DMBA developed breast cancer, which was associated with increased expression of Bcl-2 and decreased expression of Bax, caspase 3, and caspase 9 in mammary tissues. Administration of genistein and lycopene in combination was more effective in inhibiting DMBA-induced breast tumors and modulating the expression of apoptosis associated proteins than the administration of each agent alone. Our results suggest that lycopene and genistein are potent antioxidants and, when given in combination, offer maximum protection against DMBA-induced mammary carcinogenesis.

<em>Ulva lactuca</em> polysaccharides prevent Wistar rat breast carcinogenesis through the augmentation of apoptosis, enhancement of antioxidant defense system, and suppression of inflammation

“…On the other hand, the amount of expressed p53 was potentially decreased in DMBA-administered rats, whereas the amount of expressed bcl-2 was potentially increased as compared to normal control. These findings are supported by the findings of Sahin et al46 who reported that animals administered DMBA had an increased expression of bcl-2 in mammary tissues, and various subtypes of breast cancer have an elevated expression of bcl-2 among them 47. In addition, a recent study48 indicated that the DBMA-induced tumors are apparently the result of p53 inactivation as well as bcl-2 expression activation.…”

Chemopreventive Activity of Honokiol against 7, 12 - Dimethylbenz[a]anthracene-Induced Mammary Cancer in Female Sprague Dawley Rats

“…In the present study, honokiol treatment was started 2 weeks prior to the DMBA administration and continued to till the end of the study period. Chemopreventive potential of several natural products were established using similar model and was the basis for present study (Sahin et al, 2011; Bishayee et al, 2013; Mandal and Bishayee, 2015) Among the several animal models of examining promiscuous nature of breast cancer, we chose DMBA model (Barros et al, 2004). The DMBA-induced mammary cancer in rats is one of the standard preclinical animal models for studying chemopreventive drug development against breast cancer.…”

Combination of metformin and curcumin targets breast cancer in mice by angiogenesis inhibition, immune system modulation and induction of p53 independent apoptosis

“…3 Traditional disease treatments which include surgery, chemotherapy, radiotherapy and hormone therapies are not fully effective in treating breast cancer, especially in patients with an advanced stage of the disease. 3,4 Therefore, recent studies have focused on identifying alternative agents that reduce the incidence of the disease and cure it. Synthetic drugs or natural products that are highly selective and less toxic and show anticancer activity can be potential agents in breast cancer treatment.…”