Chlorogenic Acid and Cinnamaldehyde in Combination Inhibit Metastatic Traits and Induce Apoptosis via Akt Downregulation in Breast Cancer Cells.

Most reported breast cancer-associated deaths are directly correlated with metastatic disease. Additionally, the primary goal of treating metastatic breast cancer is to prolong life. Thus, there remains the need for more effective and safer strategies to treat metastatic breast cancer. Recently, more attention has been given to natural products (or phytochemicals) as potential anticancer treatments. This study aimed to investigate the synergistic effects of the combination of the phytochemicals chlorogenic acid and cinnamaldehyde (CGA and CA) toward inhibiting metastasis. The hypothesis was that CGA and CA in combination decrease the metastatic potential of breast cancer cells by inhibiting their invasive and migratory abilities as well as the induction of apoptosis via the downregulation of the Akt, disrupting its signal transduction pathway. To test this, wound-healing and Transwell™ Matrigel™ assays were conducted to assess changes in the migration and invasion properties of the cells; apoptosis was analyzed by fluorescence microscopy for Annexin V/propidium iodide; and immunoblotting and FACSort were performed on markers for the epithelial-to-mesenchymal transition status. The results show that CGA and CA significantly downregulated Akt activation by inhibiting phosphorylation. Consequently, increased caspase 3 and decreased Bcl2-α levels were observed, and apoptosis was confirmed. The inhibition of metastatic behavior was demonstrated by the attenuation of N-cadherin, fibronectin, vimentin, and MMP-9 expressions with concomitant increased expressions of E-cadherin and EpCAM. In summary, the present study demonstrated that CGA and CA in combination downregulated Akt activation, inhibited the metastatic potential, and induced apoptosis in different breast cancer cell lines.

Cadmium and nickel co-exposure exacerbates genotoxicity and not oxido-inflammatory stress in liver and kidney of rats: Protective role of omega-3 fatty acid.

The present study examined the influence of co-exposure to cadmium (Cd) and nickel (Ni) on hepatorenal function as well as the protective role of omega-3 polyunsaturated fatty acids (ω-3FA) in rats. The animals were exposed to Cd (5 mg/kg) and Ni (150 µg/L in drinking water) singly or co-exposed to both metals and ω-3FA at 20 mg/kg for 14 consecutive days. Results showed that hepatorenal injury resulting from individual exposure to Cd or Ni was not aggravated in the co-exposure group. Moreover, ω-3FA markedly abrogated the reduction in the antioxidant enzyme activities, the increase in reactive oxygen and nitrogen species, and lipid peroxidation induced by Cd and Ni co-exposure. Additionally, ω-3FA administration markedly suppressed the increase in hepatic and renal myeloperoxidase activity, nitric oxide, tumor necrosis factor alpha, and interleukin-1 ß levels in the co-exposure group. Genotoxicity resulting from individual exposure to Cd or Ni was intensified in the co-exposure group. However, ω-3FA administration markedly ameliorated the genotoxicity and histological lesions in the co-exposure group. Taken together, co-exposure to Cd and Ni aggravated genotoxicity and not oxido-inflammatory stress in the liver and kidney of rats. ω-3FA abated hepatorenal injury and genotoxicity induced by Cd and Ni co-exposure in rats.

Natural Compounds and Breast Cancer: Chemo-Preventive and Therapeutic Capabilities of Chlorogenic Acid and Cinnamaldehyde.

Globally, breast cancer is not only the most frequently diagnosed cancer but also the leading cause of cancer death in women. Depending on breast cancer histotype, conventional breast cancer treatment options vary greatly in efficacy and accompanying side effects. Thus, there is a need for more effective and safer strategies that impact breast cancer at all stages. Plant-based natural products are easily available, with them proving effective and inexpensive. Two such phytochemicals are chlorogenic acid and cinnamaldehyde. Studies have shown their efficacy against different molecular subtypes of breast cancers in vitro and in vivo. In this review, we discuss their current status in anticancer research with specific emphasis on chlorogenic acid and cinnamaldehyde. We describe their multiple mechanisms of action in destroying breast cancer cells, their potential uses, and the need for translational applications. We also include future directions for investigations to progress chlorogenic acid and cinnamaldehyde research from bench to bedside.