Interactions of imidazole antifungal agents with purified cytochrome P-450 proteins

Rodrigues, A. David; Gibson, Gordon; Ioannides, Costas; Parke, Dennis V.

doi:10.1016/0006-2952(87)90670-8

Cited by 116 publications

(43 citation statements)

References 34 publications

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“…Cip1 is involved in cell cycle exit and terminal cell differentiation (Rodrigues et al, 1987). In agreement with these findings, our results showed that the inhibition of PCa cell growth induced by the IK Ca1 inhibitor was likely to involve the accumulation of p21…”

Section: Discussionsupporting

confidence: 91%

Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

et al. 2009

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Accumulating data point to K þ channels as relevant players in controlling cell cycle progression and proliferation of human cancer cells, including prostate cancer (PCa) cells. However, the mechanism(s) by which K þ channels control PCa cell proliferation remain illusive. In this study, using the techniques of molecular biology, biochemistry, electrophysiology and calcium imaging, we studied the expression and functionality of intermediate-conductance calcium-activated potassium channels (IK Ca1 ) in human PCa as well as their involvement in cell proliferation. We showed that IK Ca1 mRNA and protein were preferentially expressed in human PCa tissues, and inhibition of the IK Ca1 potassium channel suppressed PCa cell proliferation. The activation of IK Ca1 hyperpolarizes membrane potential and, by promoting the driving force for calcium, induces calcium entry through TRPV6, a cation channel of the TRP (Transient Receptor Potential) family. Thus, the overexpression of the IK Ca1 channel is likely to promote carcinogenesis in human prostate tissue.

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Section: Discussionsupporting

confidence: 91%

Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

et al. 2009

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“…23593-75-1), our model EDC pollutant, was obtained from Sigma-Aldrich (98% pure). Clotrimazole is a widely used imidazole fungicide, which inhibits the enzyme P450(CYP)51 lanosterol 14α-demethylase and the conversion of lanosterol to ergosterol in fungal cell wall synthesis (81). The compound is also a potent ligand and inhibitor of P450(CYP)19 aromatase, which catalyses the conversion of androgens to estrogens in vertebrates, including fish (56).…”

Section: Methodsmentioning

confidence: 99%

Climate change and pollution speed declines in zebrafish populations

Brown

Owen

Peters

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Endocrine disrupting chemicals (EDCs) are potent environmental contaminants, and their effects on wildlife populations could be exacerbated by climate change, especially in species with environmental sex determination. Endangered species may be particularly at risk because inbreeding depression and stochastic fluctuations in male and female numbers are often observed in the small populations that typify these taxa. Here, we assessed the interactive effects of water temperature and EDC exposure on sexual development and population viability of inbred and outbred zebrafish (Danio rerio). Water temperatures adopted were 28°C (current ambient mean spawning temperature) and 33°C (projected for the year 2100). The EDC selected was clotrimazole (at 2 μg/L and 10 μg/L), a widely used antifungal chemical that inhibits a key steroidogenic enzyme [cytochrome P450(CYP19) aromatase] required for estrogen synthesis in vertebrates. Elevated water temperature and clotrimazole exposure independently induced maleskewed sex ratios, and the effects of clotrimazole were greater at the higher temperature. Male sex ratio skews also occurred for the lower clotrimazole exposure concentration at the higher water temperature in inbred fish but not in outbred fish. Population viability analysis showed that population growth rates declined sharply in response to male skews and declines for inbred populations occurred at lower male skews than for outbred populations. These results indicate that elevated temperature associated with climate change can amplify the effects of EDCs and these effects are likely to be most acute in small, inbred populations exhibiting environmental sex determination and/or differentiation.

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“…Sahai et al [4] have reported that fluconazole increased ZDV serum concentrations and decreased its apparent oral clearance. In addition, imidazole agents are well-known potent inhibitors of cytochrome P-450 isozymes [5][6][7][8] whereas their effect on UGT (uridine diphosphoglucuronosyltransferase) is relatively unknown.…”

Section: Introductionmentioning

confidence: 99%

Comparative effects of antifungal agents on zidovudine glucuronidation by human liver microsomes.

Sampol¹,

Lacarelle²,

Rajaonarison³

et al. 1995

Brit J Clinical Pharma

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Zidovudine (ZDV) is extensively metabolised by the liver to an inactive glucuronide (GZDV). Since ZDV is often administered with antimycotic drugs, we studied the effect of six systemic antifungal agents on the in vitro glucuronidation of ZDV by human liver microsomes. 5-fluorocytosine and itraconazole had no inhibitory effect whereas amphotericine B, ketoconazole, miconazole and fluconazole inhibited in vitro GZDV formation (Ki values were 0.13, 0.08, 0.18 and 1.4 mm respectively).

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Interactions of imidazole antifungal agents with purified cytochrome P-450 proteins

Cited by 116 publications

References 34 publications

Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

Climate change and pollution speed declines in zebrafish populations

Comparative effects of antifungal agents on zidovudine glucuronidation by human liver microsomes.

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