Abstract
Cis-diamminedichloroplatinum (II) (cisplatin) is the most widely used chemotherapeutic drug for various cancers, but its effectiveness is limited by tumor cell resistance and the severe side effects it causes. Since high level of cisplatin is cytotoxic to both cancer and normal cells, the goal of the present study was to explore the effectiveness of prolonged low doses of cisplatin in the management of leukemia. To achieve our goal, human leukemia (HL-60) cells were treated with different doses (1, 2, or 3 µM) of cisplatin for 24, 48, 72 and 96 hours. Cell viability was assessed by MTS assay. Both oxidative stress damage and genotoxicity were estimated by antioxidants, lipid peroxidation, and comet assays, respectively. Data obtained from the MTS assay demonstrated that cisplatin treatment decreased the number of viable tumor cells by direct cell killing or by simply decreasing the rate of cellular proliferation in a dose- and time-dependent fashion. The results of the lipid peroxidation showed a significant increase (p<0.05) of malondialdehyde levels with increasing cisplatin doses. Results obtained from super oxide dismutase and catalase assays showed a gradual increase in antioxidant enzyme activity in cisplatin-treated cells compared to control cells. Data generated from the Comet assay demonstrated a significant dose-dependent increase in genotoxicity with respect to DNA damage as a result of cisplatin treatment. Taken together, our research demonstrated that cisplatin-induced cytotoxicity in HL-60 cells is mediated at least in part via induction of oxidative stress and oxidative damage.
Highlights
Cisplatin, cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug and is one of the most widely used drugs for the treatment of various cancers [1,2]
Cell survival was measured in HL60 cells treated with 1, 2, or 3 μM cisplatin for 24, 48, 72, and 96 h incubation periods compared to the respective controls (Figure 1)
The results indicate that the cell viability was decreased with increased cisplatin dose and incubation period
Summary
Cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug and is one of the most widely used drugs for the treatment of various cancers [1,2]. Cisplatin is known to bind cellular components such as DNA and proteins, and to form DNA and protein adducts as a result of cross links with DNA and protein molecules that hamper transcription and translation mechanisms [6,7]. Those DNA adducts impact cell cycle progression check points and determine whether the cell has to die or survive with the help of repair mechanisms [8]. In addition to the formation of DNA adducts, cisplatin induces oxidative stress, and modulates calcium signaling, and cell apoptosis [9,10]. Cisplatin mediates the mitogen activated protein kinases (MAPK) and jun amino-terminal kinase (JNK) pathways that coordinate various extra cellular signals to regulate cell growth, survival, and apoptosis [13,14]
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