Abstract
Cis-diammine dichloroplatinum (CDDP) is one of the most important chemotherapeutic agents for cancer treatment. Nonetheless, its notable side effect, nephrotoxicity, undermines its clinical use. The current study was undertaken to evaluate the protective potential of the aqueous extract (AEC) of Cinnamomum cassia (cinnamon) against the cytotoxic effect of CDDP in vitro and to elaborate the molecular mechanism underlying protection. MTT assay was performed to assess viability of the normal kidney Vero cells treated with CDDP and/or AEC. Cells were stained with Coomassie blue, acridine orange and ethidium bromide to highlight morphological features of apoptosis. Caspase-3 activity, DNA fragmentation and reactive oxygen species (ROS) level were monitored to assess biochemical hallmarks of apoptosis. Quantitative RT-PCR and Western blot analyses were performed to elucidate expression of cellular molecules underlying the protective potential of AEC. CDDP-treated Vero cells exhibited hallmarks of apoptosis; these hallmarks were significantly suppressed in the presence of AEC. AEC did not alter activity of CDDP-induced cytotoxicity of breast and liver cancer cells. AEC treatment of Vero cells prevented CDDP-induced increased expression of mitochondrial Bax protein, release of mitochondrial cytochrome c, caspase-3 activation, DNA fragmentation and generation of ROS. AEC up-regulated expression of the cytoprotective gene (heme oxygenase (HO)-1). These findings suggest AEC has protective effects against CDDP-induced toxicity via preventing the activation of various cellular mechanisms mediating apoptotic cell death, without compromising the anticancer efficiency of CDDP. Thus, cinnamon may represent one of the most feasible ways to reduce the risk of CDDP-induced toxicity.
Highlights
Cis-diamminedichloroplatinum, Cisplatin (CDDP), is one of the most widely used chemotherapeutic agents for the treatment of several human malignancies
Cinnamon may represent one of the most feasible ways to reduce the risk of Cis-diammine dichloroplatinum (CDDP)-induced toxicity
Constituents of aqueous extract (AEC) resulting from the Gas chromatography–mass spectrometry (GC-MS) and High-performance liquid chromatography (HPLC) analysis
Summary
Cis-diamminedichloroplatinum, Cisplatin (CDDP), is one of the most widely used chemotherapeutic agents for the treatment of several human malignancies. Various approaches have been attempted to curtail these side effects such as using the novel CDDP analogues and hydrating the patients during CDDP treatment[2] Despite these efforts, CDDP-induced nephrotoxicity remains a major obstacle that limits its use and efficacy in cancer therapy[3]. On the activation of the latter caspase, the cleavage of cellular machineries essential for cell viability cascades This results in shrinkage of the cell and fragmentation into membrane-bound apoptotic bodies, which are eventually subjected to rapid phagocytosis by the surrounding cells[6]. New approaches, such as novel effective drugs with mild toxicities or excellent combination regimens, are needed to ameliorate CDDP side effects
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