P2Y12 receptor inhibition augments cytotoxic effects of cisplatin in breast cancer

Sarangi, Sasmit; Pandey, Ambarish; Papa, Anne Laure; Sengupta, Poulomi; Kopparam, Jawahar; Dadwal, Ushashi C.; Basu, Sudipta; Sengupta, Shiladitya

doi:10.1007/s12032-013-0567-y

Cited by 22 publications

(16 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Other authors also showed that 4T1 cells expressed P2Y12 receptors and when co-incubated in vitro with CDDP and P2Y12 inhibitor, significantly higher cytotoxic response in 4T1 cancer cell line was observed. However, CDDP in these studies increased P2Y12 receptor expression on cancer cells [ 34 ], which was found to be disadvantageous, because P2Y12 receptors agonists were shown to stimulate the proliferation of glioma cells [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Clopidogrel in a combined therapy with anticancer drugs—effect on tumor growth, metastasis, and treatment toxicity: Studies in animal models

et al. 2017

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Clopidogrel in a combined therapy with anticancer drugs—effect on tumor growth, metastasis, and treatment toxicity: Studies in animal models

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Second, DCA inhibits the four pyruvate dehydrogenase kinase isoforms to different extents, 68 therefore, the relative expression and distribution of these isoforms will determine DCA sensitivity, and 4T1 cells may have a pyruvate dehydrogenase kinase isoform distribution that is unfavorable for inhibition by DCA. Finally, it has been demonstrated that CP induces hypoxia-inducible factor 1-alpha (HIF1-a) in 4T1 cells 69 and that inhibition of HIF1-a is a requirement for sensitivity to DCA. 70 Therefore, induction of HIF1-a by CP in 4T1 cells may prevent DCA from sensitizing these cells to apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Dichloroacetate Prevents Cisplatin-Induced Nephrotoxicity without Compromising Cisplatin Anticancer Properties

Galgamuwa¹,

Hardy

Dahlstrom

et al. 2016

JASN

View full text Add to dashboard Cite

Cisplatin is an effective anticancer drug; however, cisplatin use often leads to nephrotoxicity, which limits its clinical effectiveness. In this study, we determined the effect of dichloroacetate, a novel anticancer agent, in a mouse model of cisplatin-induced AKI. Pretreatment with dichloroacetate significantly attenuated the cisplatin-induced increase in BUN and serum creatinine levels, renal tubular apoptosis, and oxidative stress. Additionally, pretreatment with dichloroacetate accelerated tubular regeneration after cisplatin-induced renal damage. Whole transcriptome sequencing revealed that dichloroacetate prevented mitochondrial dysfunction and preserved the energy-generating capacity of the kidneys by preventing the cisplatin-induced downregulation of fatty acid and glucose oxidation, and of genes involved in the Krebs cycle and oxidative phosphorylation. Notably, dichloroacetate did not interfere with the anticancer activity of cisplatin in vivo. These data provide strong evidence that dichloroacetate preserves renal function when used in conjunction with cisplatin.

show abstract

“…P2Y 12 has been found in glioma and astrocytoma cells [61,62]. P2Y 12 expression has been also described in breast cancer cell lines and was upregulated by cell treatment with cisplatin [63]. In those cells, co-administration of P2Y 12 inhibitor with cisplatin resulted in significantly higher cytotoxic response [63].…”

Section: Role Of Non-platelet P2y 12 Receptorsmentioning

confidence: 95%

P2Y12 Inhibition beyond Thrombosis: Effects on Inflammation

Gaussem

Bachelot‐Loza

Nesseler

et al. 2020

IJMS

View full text Add to dashboard Cite

The P2Y12 receptor is a key player in platelet activation and a major target for antithrombotic drugs. The beneficial effects of P2Y12 receptor antagonists might, however, not be restricted to the primary and secondary prevention of arterial thrombosis. Indeed, it has been established that platelet activation also has an essential role in inflammation. Additionally, nonplatelet P2Y12 receptors present in immune cells and vascular smooth muscle cells might be effective players in the inflammatory response. This review will investigate the biological and clinical impact of P2Y12 receptor inhibition beyond its platelet-driven antithrombotic effects, focusing on its anti-inflammatory role. We will discuss the potential molecular and cellular mechanisms of P2Y12-mediated inflammation, including cytokine release, platelet–leukocyte interactions and neutrophil extracellular trap formation. Then we will summarize the current evidence on the beneficial effects of P2Y12 antagonists during various clinical inflammatory diseases, especially during sepsis, acute lung injury, asthma, atherosclerosis, and cancer.

show abstract

P2Y12 receptor inhibition augments cytotoxic effects of cisplatin in breast cancer

Cited by 22 publications

References 22 publications

Clopidogrel in a combined therapy with anticancer drugs—effect on tumor growth, metastasis, and treatment toxicity: Studies in animal models

Clopidogrel in a combined therapy with anticancer drugs—effect on tumor growth, metastasis, and treatment toxicity: Studies in animal models

Dichloroacetate Prevents Cisplatin-Induced Nephrotoxicity without Compromising Cisplatin Anticancer Properties

P2Y12 Inhibition beyond Thrombosis: Effects on Inflammation

Contact Info

Product

Resources

About