Clopidogrel in a combined therapy with anticancer drugs-effect on tumor growth, metastasis, and treatment toxicity: Studies in animal models.
Agnieszka DenslowMarta ŚwitalskaJoanna JaroszDiana PapiernikKseniia PorshnevaMarcin NowakJoanna WietrzykPublished in: PloS one (2017)
Clopidogrel, a thienopyridine derivative with antiplatelet activity, is widely prescribed for patients with cardiovascular diseases. In addition to antiplatelet activity, antiplatelet agents possess anticancer and antimetastatic properties. Contrary to this, results of some studies have suggested that the use of clopidogrel and other thienopyridines accelerates the progression of breast, colorectal, and prostate cancer. Therefore, in this study, we aimed to evaluate the efficacy of clopidogrel and various anticancer agents as a combined treatment using mouse models of breast, colorectal, and prostate cancer. Metastatic dissemination, selected parameters of platelet morphology and biochemistry, as well as angiogenesis were assessed. In addition, body weight, blood morphology, and biochemistry were evaluated to test toxicity of the studied compounds. According to the results, clopidogrel increased antitumor and/or antimetastatic activity of chemotherapeutics such as 5-fluorouracil, cyclophosphamide, and mitoxantrone, whereas it decreased the anticancer activity of doxorubicin, cisplatin, and tamoxifen. The mechanisms of such divergent activities may be based on the modulation of tumor vasculature via factors, such as transforming growth factor β1 released from platelets. Moreover, clopidogrel increased the toxicity of docetaxel and protected against mitoxantrone-induced toxicity, which may be due to the modulation of hepatic enzymes and protection of the vasculature, respectively. These results demonstrate that antiplatelet agents can be useful but also dangerous in anticancer treatment and therefore use of thienopyridines in patients undergoing chemotherapy should be carefully evaluated.
Keyphrases
- acute coronary syndrome
- prostate cancer
- percutaneous coronary intervention
- antiplatelet therapy
- transforming growth factor
- patients undergoing
- body weight
- cardiovascular disease
- oxidative stress
- squamous cell carcinoma
- radical prostatectomy
- epithelial mesenchymal transition
- mouse model
- small cell lung cancer
- coronary artery disease
- low dose
- stem cells
- type diabetes
- endothelial cells
- bone marrow
- combination therapy
- mesenchymal stem cells
- drug induced
- breast cancer cells
- red blood cell
- cancer therapy
- smoking cessation
- cell therapy