Abstract
Bioactive compounds from plants represent good candidate drugs for the prevention and treatment of various forms of cancer. Berries are rich sources of bioactive compounds, and there has been an increasing interest in the study of therapeutic action of wild berries. Oxidants are generated continuously in biological system as a result of physiological process. When there is an imbalance between oxidants and antioxidants, it leads to a condition called oxidative stress. Natural compounds as inducers of oxidative stress are able to modulate the physiological functions of cancer cells leading to cell death or survival. The aim of this study was to evaluate the induction of apoptosis by isolated bioactive compounds (1-(2-hydroxyphenyl)-4-methylpentan-1-one (C1) and 2-[(3-methylbutoxy) carbonyl] benzoic acid (C2)) from Rubus fairholmianus against MCF-7 breast cancer cells. The exposure of C1 and C2 reduced viability (IC50 of C1: 4.69; C2: 8.36 μg/mL) and proliferation. Cytochrome c release from mitochondria and changes in mitochondrial membrane potential of treated cells supported the intrinsic apoptotic cell death. Reactive oxygen species (ROS) production after treatment with C1 and C2 was found to be higher and induced nuclear damage. Expression of apoptotic proteins after the treatments was significantly upregulated as indicated using immunofluorescence (caspase 9, p53, and Bax), western blotting (p53, cleaved PARP, cytochrome c, and Bax), and ELISA (caspase 9) analysis. Overall, C1 was more cytotoxic, increased the ROS production in dichlorodihydrofluorescein diacetate assay, and induced apoptosis in breast cancer cells. These results illustrate that berry bioactive compounds have strong chemopreventive potential. In this article, we provide information on prooxidant and anticancer activities of Rubus bioactive compounds. Natural products have always demonstrated a significant contribution to the development of several cancer chemotherapeutic drugs. Most of these compounds are known to affect the redox state of the cell; and studies on these compounds have focused on their antioxidant property instead of prooxidant properties.
Highlights
Cancer is the leading cause of death in both developing and developed countries
Morphological variations in MCF-7 cells followed by the treatment with Compounds 1-(2-hydroxyphenyl)-4-methylpentan-1-one (C1) and C2 were compared with control cells (Figures 2(a)–2(g)) and WS1 fibroblast normal cells (Figures 3(a)–3(g))
Total loss of membrane integrity and detachment from the culture plate were observed in the cells treated with C1 and C2
Summary
Cancer is the leading cause of death in both developing and developed countries. Globally, cancers of the lung, breast, colon/rectum, and prostate are the most common types. Breast cancer is the most predominant, hormone-associated malignancy in women. The prevalence of breast cancer is growing in developing countries. Upregulation of growth hormone receptors such as estrogen in breast cells is the key reason and the stimulating factor for the development of breast cancer [1]. About 80-85% of worldwide population rely on traditional plant-based medicines for their health care needs. A number of plant extracts, isolated compounds, and their analogues have been used as effective anticancer drugs, and there has been an increasing interest in the study of therapeutic properties of plant-derived compounds [2]. The characterization and analysis of therapeutic values of plant extracts and the isolated bioactive compounds are a growing area of research. Epidemiological studies show that diets rich in plant-based foods protect against many diseases including
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