The cytotoxic activity of Taxol in primary cultures of tumour cells from patients is partly mediated by Cremophor EL

Nygren, Peter; Csòka, Katalin; Jönsson, Bertil; Fridborg, H; Bergh, Jonas; Hagberg, Hans; Glimelius, Bengt; Brodin, Ola; Tholander, Bengt; Kreuger, A

doi:10.1038/bjc.1995.97

Cited by 41 publications

(8 citation statements)

References 18 publications

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“…Values are means + SD of six mice (Ht hematocrit, WBC white blood cells, BUN blood urea nitrogen, SCr serum creatinine) Saline CR CDDP CDDP + CR Ht (%) 41 ±2.5 42 ±3.0 31 ±3.0* , ** 38 ±3.5*** WBC (10 -3 mm 3 ) 9.56±1.0 8.07±0.7 6.57±0.5* , ** 8.30±0.7*** BUN (mg/dl) 22 ±3.5 21 ±4.0 55 ±6.0* , ** 51 ±4.7* , ** SCr (mg/dl) 0.6 ±0.09 0.55±0.07 1.3 ±0.2* , ** 1.1 ±0.17* , ** * , ** , ***Significant difference from saline, CR or CDDP groups at P<0.05, respectively, using ANOVA followed by Tukey-Kramer multiple comparison test In vitro experiments showed that CR enhanced the cytotoxicity of CDDP against cultured EAC cells, an effect that was not associated with a parallel increase in CDDP cellular accumulation. This observation is in accordance with several studies demonstrating that CR can significantly enhance the cytotoxicity of doxorubicin (DOX; Badary et al 1998) and paclitaxel (Nygren et al 1995) in primary cultures of tumor cells. It could be suggested that CR makes tumor cells more vulnerable to the action of CDDP and hence enhances its cytotoxicity.…”

Section: Discussionsupporting

confidence: 93%

Differential alteration of cisplatin cytotoxicity and myelotoxicity by the paclitaxel vehicle cremophor EL

Badary

Abdel-Naim

Khalifa

et al. 2000

Naunyn-Schmiedeberg's Arch Pharmacol

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Cremophor EL (CR), the paclitaxel vehicle, has previously been reported to alter the pharmacokinetics and/or pharmacodynamics of some anticancer drugs including paclitaxel. Several experimental and clinical studies suggested that cisplatin (CDDP) in combination with paclitaxel results in less hematological toxicity than anticipated. To reveal the role of CR in this important pharmacological interaction, we evaluated the interaction of CR with CDDP in vitro and in vivo using experimental Ehrlich ascites carcinoma (EAC) tumor. CR (1 microg/ml) significantly enhanced the in vitro cytotoxicity of CDDP in cultured EAC cells. This enhancement was not associated with a parallel increase in CDDP cellular uptake. In tumor-bearing mice, CR (2.5 ml/kg, i.v.) given in combination with CDDP (7 mg/kg, i.v.) did not significantly change CDDP pharmacokinetics, antitumor activity or nephrotoxicity. On the other hand, CDDP-induced hematological toxicity was significantly reduced by CR. This protective effect was related to CR-induced inhibition of cellular CDDP accumulation in bone marrow. This study presents evidence that CR may play an important role in the pharmacological interaction between CDDP and paclitaxel. The present data may suggest formulation of CDDP with CR for systemic treatment. Further studies are yet necessary to establish the clinical value of CR as a modifier for CDDP therapeutic index.

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Section: Discussionsupporting

confidence: 93%

Differential alteration of cisplatin cytotoxicity and myelotoxicity by the paclitaxel vehicle cremophor EL

Badary

Abdel-Naim

Khalifa

et al. 2000

Naunyn-Schmiedeberg's Arch Pharmacol

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“…sociated with peroxidation of polyunsaturated fatty acids and with direct disturbing effect in the cell membrane (Nygren et al 1995, Burton 1991, Bégin et al 1988). …”

Section: Strain Genotypementioning

confidence: 99%

Cremophor EL stimulates mitotic recombination in uvsH//uvsH diploid strain of Aspergillus nidulans

Busso

Castro-Prado

2004

An. Acad. Bras. Ciênc.

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Cremophor EL is a solubilizer and emulsifier agent used in the pharmaceutical and foodstuff industries. The solvent is the principal constituent of paclitaxel's clinical formulation vehicle. Since mitotic recombination plays a crucial role in multistep carcinogenesis, the study of the recombinagenic potential of chemical compounds is of the utmost importance. In our research genotoxicity of cremophor EL has been studied by using an uvsH//uvsH diploid strain of Aspergillus nidulans. Since it spends a great part of its cell cycle in the G2 period, this fungus is a special screening system for the study of mitotic recombination induced by chemical substances. Homozygotization Indexes (HI) for paba and bi markers from heterozygous B211//A837 diploid strain were determined for the evaluation of the recombinagenic effect of cremophor EL. It has been shown that cremophor EL induces increase in mitotic crossing-over events at nontoxic concentrations (0.05 and 0.075% v/v).

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“…Cytotoxicity of Cremophor EL was confirmed in doxorubicin-resistant human breast cancer cell lines and various human tumor samples. [21][22][23] It was postulated that formation of free radicals submit your manuscript | www.dovepress.com…”

Section: Cytotoxicity Of Blank Pmsmentioning

confidence: 99%

Lx2-32c–loaded polymeric micelles with small size for intravenous drug delivery and their inhibitory effect on tumor growth and metastasis in clinically associated 4T1 murine breast cancer

Chen

Huang

Gao

et al. 2016

IJN

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Lx2-32c is a novel taxane derivative with a strong antitumor activity. In this study, we developed Lx2-32c–loaded polymeric micelles (Lx2-32c-PMs) with small size and investigated their antitumor efficacy against tumor growth and metastasis on 4T1 murine breast cancer cell line with Cremophor EL–based Lx2-32c solution as the control. In this study, copolymer monomethoxy polyethylene glycol 2000 –polylactide 1300 was used to prepare Lx2-32c-PMs by film hydration method, and their physicochemical properties were characterized as well, according to morphology, particle size, zeta potential, in vitro drug release, and reconstitution stability. Under confocal laser scanning microscopy, it was observed that Lx2-32c-PMs could be effectively taken up by 4T1 cells in a time-dependent manner. Cell Counting Kit-8 assay showed that the IC 50 of Lx2-32c-PMs was 0.3827 nM. Meanwhile, Lx2-32c-PMs had better ability to promote apoptosis and induce G 2 /M cycle block and polyploidy formation, compared with Lx2-32c solution. More importantly, in vivo animal studies showed that compared to Lx2-32c solution, Lx2-32c-PMs possessed better ability not only to effectively inhibit the tumor growth, but also to significantly suppress spontaneous and postoperative metastasis to distant organs in 4T1 orthotopic tumor-bearing mice. Consequently, Lx2-32c-PMs have significantly prolonged the survival lifetime of tumor-bearing mice. Thus, our study reveals that Lx2-32c-PMs had favorable antitumor activity and exhibited a good prospect for application in the field of antitumor therapy.

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The cytotoxic activity of Taxol in primary cultures of tumour cells from patients is partly mediated by Cremophor EL

Cited by 41 publications

References 18 publications

Differential alteration of cisplatin cytotoxicity and myelotoxicity by the paclitaxel vehicle cremophor EL

Differential alteration of cisplatin cytotoxicity and myelotoxicity by the paclitaxel vehicle cremophor EL

Cremophor EL stimulates mitotic recombination in uvsH//uvsH diploid strain of Aspergillus nidulans

Lx2-32c–loaded polymeric micelles with small size for intravenous drug delivery and their inhibitory effect on tumor growth and metastasis in clinically associated 4T1 murine breast cancer

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The cytotoxic activity of Taxol in primary cultures of tumour cells from patients is partly mediated by Cremophor EL

Cited by 41 publications

References 18 publications

Differential alteration of cisplatin cytotoxicity and myelotoxicity by the paclitaxel vehicle cremophor EL

Differential alteration of cisplatin cytotoxicity and myelotoxicity by the paclitaxel vehicle cremophor EL

Cremophor EL stimulates mitotic recombination in uvsH//uvsH diploid strain of Aspergillus nidulans

Lx2-32c&ndash;loaded polymeric micelles with small size for intravenous drug delivery and their inhibitory effect on tumor growth and metastasis in clinically associated 4T1 murine breast cancer

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About

Lx2-32c–loaded polymeric micelles with small size for intravenous drug delivery and their inhibitory effect on tumor growth and metastasis in clinically associated 4T1 murine breast cancer