Liarozole potentiates the cancer chemopreventive activity of and the up-regulation of gap junctional communication and connexin43 expression by retinoic acid and beta-carotene in 10T1/2 cells.

  title={Liarozole potentiates the cancer chemopreventive activity of and the up-regulation of gap junctional communication and connexin43 expression by retinoic acid and beta-carotene in 10T1/2 cells.},
  author={P Acevedo and John S. Bertram},
  volume={16 9},
Liarozole has been reported to inhibit P450 enzymes responsible for the catabolism of retinoic acid. This suggests that it may increase the effectiveness of cancer chemopreventive agents, such as retinoic acid, and pro-vitamin A carotenoids, such as beta-carotene, which may yield retinoids. To test this we have utilized the 10T1/2 cell assay system of neoplastic transformation. Simultaneous treatment with Liarozole (10(-5) M) potentiated by a factor of 1000 the ability of low concentrations of… 

Cancer prevention by retinoids and carotenoids: independent action on a common target.

The antiproliferative activity of all-trans-retinoic acid catabolites and isomers is differentially modulated by liarozole-fumarate in MCF-7 human breast cancer cells.

Findings show that liarozole-fumarate acts as a versatile inhibitor of retinoid catabolism in that it not only blocks the breakdown of ATRA, but also inhibits the catabolic pathway of 4-oxo-ATRA and 5,6-epoxy-ATra, thereby enhancing their antiproliferative activity.

Lycopene inhibits proliferation and enhances gap-junction communication of KB-1 human oral tumor cells.

The hypothesis that carotenoids in general, and lycopene in particular, may be effective anticarcinogenic agents in oral carcinogenesis is further supported.

Upregulation of Connexin 43 by Retinoids but Not by Non-Provitamin A Carotenoids Requires RARs

Simultaneous treatment with the maximally effective concentration of a retinoid and with β-carotene or the non-provitamin A carotenoid astaxanthin resulted in supraadditive upregulation of Cx43 expression, again indicating separate mechanisms of gene regulation by these two cancer preventive agents.

Proposed role of gap junctional communication in retinoid-induced suppression of proliferation and inhibition of neoplastic transformation

Effects of retinoids on gap junctional communication and the potential role of enhanced communication in decreasing proliferation of target cells and thus reducing their potential for neoplastic progression are described.

Transcriptional regulation of connexin 43 expression by retinoids and carotenoids: Similarities and differences

The retinoic acid receptor antagonist Ro 41‐5253 was capable of suppressing retinoid‐induction Cx43 luciferase reporter construct in F9 cells, but did not suppress reporter activity induced by the non‐pro‐vitamin A carotenoids astaxanthin or lycopene, indicating that retinoids have separate mechanisms of gene activation than non‐ pro‐v vitamin A carOTenoids.

Comparative Effects of All-trans β-Carotene vs. 9-cis β-Carotene on Carcinogen-Induced Neoplastic Transformation and Connexin 43 Expression in Murine 10T1/2 Cells and on the Differentiation of Human Keratinocytes

It is suggested that 9-cis retinoic acid is, in general, much more potent than the all-trans isomer, and that little or no conversion from the carotenoid to the retinoid under these culture conditions is suggested.

Study on Cytochrome P-450 Dependent Retinoic Acid Metabolism and its Inhibitors as Potential Agents for Cancer Therapy

A wide range of established P-450 inhibitors has been screened to examine their inhibitory activity on all-trans-Retinoic acid (ATRA) metabolism and results indicate that mostly azoles with substituents in positions other than the 1-position on the ring are very weak inhibitors of RA metabolism.

Differential effects of TPA and retinoic acid on cell-cell communication in human bronchial epithelial cells.

The studies show that an uncoupling of GJC and cell proliferation is associated with a differential response to the growth inhibitory effects of RA and phorbol esters in immortalized compared to primary human bronchial epithelial cells.

Retinoids and their receptors in cancer development and chemoprevention.