Abstract
It is supposed that plant functional foods, rich in phytochemicals, may potentially have preventive effects in carcinogenesis. In this study, the anticancer effects of cloves in the in vivo and in vitro mammary carcinoma model were assessed. Dried flower buds of cloves (CLOs) were used at two concentrations of 0.1% and 1% through diet during 13 weeks after the application of chemocarcinogen. After autopsy, histopathological and immunohistochemical analyses of rat mammary carcinomas were performed. Moreover, in vitro evaluation using MCF‐7 cells was carried out. Dietary administered CLO caused the dose‐dependent decrease in tumour frequency by 47.5% and 58.5% when compared to control. Analysis of carcinoma cells in animals showed bcl‐2, Ki67, VEGFA, CD24 and CD44 expression decrease and Bax, caspase‐3 and ALDH1 expression increase after high‐dose CLO administration. MDA levels were substantially decreased in rat carcinomas in both CLO groups. The evaluation of histone modifications revealed increase in lysine trimethylations and acetylations (H4K20me3, H4K16ac) in carcinomas after CLO administration. TIMP3 promoter methylation levels of CpG3, CpG4, CpG5 islands were altered in treated cancer cells. An increase in total RASSF1A promoter methylation (three CpG sites) in CLO 1 group was found. In vitro studies showed antiproliferative and pro‐apoptotic effects of CLO extract in MCF‐7 cells (analyses of cytotoxicity, Brdu, cell cycle, annexin V/PI, caspase‐7, Bcl‐2 and mitochondrial membrane potential). This study showed a significant anticancer effect of clove buds in the mammary carcinoma model in vivo and in vitro.
Highlights
It is well documented that regular consumption of phytochemicals from whole foods is linked with a risk reduction of the diseases of civilization, including cancer [1]
Several recent epidemiological studies revealed that long-term consumption of plant-derived functional foods is linked with a decreased risk of breast carcinoma [5,6,7]
Despite the fact that single phytochemicals demonstrated significant antioxidant and anticancer effects in several studies using different cancer cell lines [19,20,21], we have found that resveratrol administered alone did not indicate any anticancer effects in two repeated studies using the same model of mammary carcinogenesis in rats [22, 23]
Summary
It is well documented that regular consumption of phytochemicals from whole foods (functional foods) is linked with a risk reduction of the diseases of civilization, including cancer [1]. Plethora of studies demonstrated that phenolics, carotenoids and other plant chemicals display anticancer and several other biological activities, for example antioxidant, anti-inflammatory or immunomodulatory [2]. Several recent epidemiological studies revealed that long-term consumption of plant-derived functional foods is linked with a decreased risk of breast carcinoma [5,6,7]. CLOs (Syzygium aromaticum L.) are spices which consist of a mixture of phytochemicals —phenolic acids, flavonol glucosides, tannins and phenolic volatile oils (eugenol, acetyl eugenol) with the highest antioxidant activity among plant functional foods [8, 9]. The positive activity of clove’s extract in terms of anticancer effects in breast carcinoma has been documented in only a few in vitro studies. Different extracts of CLOs (S. aromaticum) demonstrated significant cytotoxic activity against several cancer cell lines, including MDA-MB-231 and MCF-7 breast carcinoma cell lines [10]. Authors concluded that CLOs showed excellent cytotoxicity towards MCF-7 cells [8]
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