Identification of Effective Retinoids for Inhibiting Growth and Inducing Apoptosis in Bladder Cancer Cells

Abstract

The results demonstrate that 4HPR is the most potent growth inhibitor and apoptosis inducer of the retinoids tested. Lack of retinoic acid receptor beta expression may be responsible for cell resistance to all-trans-retinoic acid but not to the other retinoids.

Inhibition of N-(4-hydroxyphenyl)retinamide-Induced Apoptosis in Breast Cancer Cells by Galectin-3

“…[1][2][3][4][5][6][7][8][9] 4HPR has been evaluated in clinical studies for prevention of breast, ovarian, cervical, oral, prostate and lung cancers. [10][11][12][13][14][15] Beneficial clinical effects of 4HPR have been observed in prevention of breast and ovarian cancers, and oral lesions, while little or no activity in treatment of high-grade squamous intraepithelial lesions in the cervix and lung or in the treatment of prostate cancer was observed.…”

“…It has been suggested that nuclear retinoid receptors, ROS, ceramide, disruption of mitochondrial transmembrane potential, and some not yet identified signals could mediate 4HPR-induced apoptosis. [3][4][5][6][7][8] Recent in vitro studies with several types of cancer cell lines suggested that ROS generation that results from perturbation in the mitochondrial respiratory chain is an important early event in 4HPR-induced apoptosis, which leads to release of cytochrome c, increased caspase-3 activity, and cell death. [4][5][6][7][8][9] It is thought that the reason for the lack of effect of 4HPR in some of the clinical trials is that the levels obtained at the 200 mg/day dose were too low to induce apoptosis.…”

“…[3][4][5][6][7][8] Recent in vitro studies with several types of cancer cell lines suggested that ROS generation that results from perturbation in the mitochondrial respiratory chain is an important early event in 4HPR-induced apoptosis, which leads to release of cytochrome c, increased caspase-3 activity, and cell death. [4][5][6][7][8][9] It is thought that the reason for the lack of effect of 4HPR in some of the clinical trials is that the levels obtained at the 200 mg/day dose were too low to induce apoptosis. 16 Indeed, the peak plasma levels reported in the clinical trials ranged from 0.2 to 1 µM, 17 whereas concentrations of >3 µM are usually required to induce apoptosis in cultured cancer cells.…”

“…16 Indeed, the peak plasma levels reported in the clinical trials ranged from 0.2 to 1 µM, 17 whereas concentrations of >3 µM are usually required to induce apoptosis in cultured cancer cells. [1][2][3][4][5][6][7][8][9]16 It is possible that higher doses are required to overcome endogenous resistance mechanisms. Among the mechanisms that render cancer cells resistant to proapoptotic agents is the increased expression of anti-apoptotic proteins such as certain members of the Bcl-2 family (e.g., Bcl-2, Bcl-xl, Bad, and Mcl-1).…”

4‐HPR modulates gene expression in ovarian cells

“…normal and high risk patients as well as cancer patients need to use specifics concentrations. 8,63,[65][66][67] Most of the clinical trials for prevention use the dose of 200 mg/day based on a breast cancer chemoprevention trial. 5 Compared with the bladder, cervix and ovary, the breast is fat tissue that stores retinoids; consequently, the local concentration of 4-HPR in the breast is conceivably higher than that in other organs and this local concentration varies from organ to organ.…”