Dipyridamole increases the cytotoxicity of cisplatin in human larynx cancer cells in vitro

Rodrigues, Michele; Júnior, Forgiarini; Perussi, Janice Rodrigues

doi:10.1590/s0100-879x2004000400017

Cited by 14 publications

(9 citation statements)

References 22 publications

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“…We have previously reported that the inhibition of PDE5 by vardenafil and sildenafil increases the concentrations of chemotherapeutics in brain tumors (7, 8). Moreover, others have reported that dipyridamole increases cisplatin concentrations and toxicity in breast carcinoma cells (18), larynx cancer cells (19), and ovarian carcinoma cells (20). In this study, we have extended those previous findings by demonstrating the desirable effects of PDE inhibitors on chemoresponse in a variety of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Modulation of Cytotoxicity and Cellular Uptake of Anti-cancer Drugs by PDE5 Inhibitors in Lung Cancer Cells

Shu

2013

Pharm Res

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Purpose Previous research has led to the recognition of a cGMP signaling pathway governing drug transport. This study is to investigate whether inhibitors of phosphodiesterase type 5 (PDE5), which increase intracellular cGMP levels, modulate the cytotoxicity and uptake of anti-cancer drugs in cancer cells. Methods The experiments were conducted with and without PDE5 inhibitors: dipyridamole, vardenafil, and/or sildenafil. The cytotoxicity of doxorubicin, cisplatin and oxaliplatin was determined in multiple cancer cell lines derived from different tissues. The cellular uptake of structurally diverse compounds was further examined in lung cancer cells with and without various endocytotic inhibitors. The tumor accumulation and the anti-tumor effect of trastuzumab were examined in a lung cancer xenograft mouse model. Results Dipyridamole could modulate the cytotoxicity of doxorubicin, cisplatin, and oxaliplatin in cancer cells. Particularly, PDE5 inhibitors increased cellular uptake of structurally diverse compounds into lung cancer cells both in vitro and in vivo. The effect of vardenafil on drug uptake could be blocked by endocytotic inhibitors. The growth of lung cancer xenograft in nude mice was significantly suppressed by addition of vardenafil to trastuzumab treatment. Conclusion PDE5 inhibitors may increase the efficacy of anti-cancer drugs by increasing endocytosis-mediated cellular drug uptake, and thus serve as adjuvant therapy for certain cancers such as lung cancer.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Modulation of Cytotoxicity and Cellular Uptake of Anti-cancer Drugs by PDE5 Inhibitors in Lung Cancer Cells

Shu

2013

Pharm Res

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“…These results were in accordance with the previously published results. 16,17 The results of treatments with AdCMV-p21, chemotherapeutics and combination treatments are shown in Figure 3. The combined treatment with AdCMV-p21 at an MOI of 40 and cisplatin (0.25-5 mg ml…”

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confidence: 99%

A dual role of p21waf1/cip1 gene in apoptosis of HEp-2 treated with cisplatin or methotrexate

2008

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We investigated the effects of p21 waf1/cip1 gene overexpression in human laryngeal squamous carcinoma cells HEp-2 lacking p53protein expression on apoptosis induction upon the treatment with two commonly used chemotherapeutic agents, cisplatin and methotrexate. For that purpose, we employed cDNA arrays and qPCR to monitor gene expression upon treatment with AdCMV-p21 alone or in combination with the chemotherapeutic compounds. We found that p21 waf1/cip1 gene overexpression provoked apoptosis of HEp-2 through the induction of the TNFRSF9 gene and activation of caspase 7. In addition, we have proved that p21 waf1/cip1 can assume a dual role in apoptosis in the same cell system depending on the chemotherapeutic agent: its overexpression enhances apoptosis in cisplatin-treated cells and attenuates apoptotic signals in methotrexate-treated cells. The observed dual role of p21 waf1/cip1 was in direct correlation with the modulation of caspases 3 and 7 activation and changes in the expression of GADD45a gene. The results presented herein encourage future use of targeted p21 waf1/cip1 gene therapy in cancer treatment in a well-defined therapeutic and genetic context.

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“…This human cell line was originally obtained from a 57-year-old man with a primary tumor of the larynx. Its biological and chemical sensitivity has been very well documented [20][21][22][23].…”

Section: Cell Linesmentioning

confidence: 99%

Cytotoxic and inhibitory activity of ceramide on cancer cell lines

Maleek¹

2010

JBiSE

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The inhibitory activity of ceramide on cancer cells was evaluated and its cytotoxicity on different cancer cell lines was measured. Ceramide was separated from bovine brain and spinal cord, and extracted by organic solvents. The crude extract was purified by using silicic acid column. Detection and identification of purified extract were carried out by using three assays: visualization, spectrophotometry and infrared. Cytotoxic effect of different concentrations (7, 15, 30 and 60 μM) of ceramide on HEp-2, RD , AMGM5, REFAM3 and AMN3 cancer cell lines was studied. Results showed that ceramide at 30 μM imposed cytotoxic activity on all cancer cell lines especially on AMGM5. Effect of ceramide at 30 μM on cell division of human lymphocyte was also examined. Significant reductions in mitotic and blast indices were observed. In addition, No genotoxic effects or chromosomal aberration were detected in lymphocyte chromosomes when ceramide was tested in vitro.

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Dipyridamole increases the cytotoxicity of cisplatin in human larynx cancer cells in vitro

Cited by 14 publications

References 22 publications

Pharmacological Modulation of Cytotoxicity and Cellular Uptake of Anti-cancer Drugs by PDE5 Inhibitors in Lung Cancer Cells

Pharmacological Modulation of Cytotoxicity and Cellular Uptake of Anti-cancer Drugs by PDE5 Inhibitors in Lung Cancer Cells

A dual role of p21waf1/cip1 gene in apoptosis of HEp-2 treated with cisplatin or methotrexate

Cytotoxic and inhibitory activity of ceramide on cancer cell lines

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