Role of Retinoids in Differentiation and Carcinogenesis* (original) (raw)
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Retinoids and their biological effects against cancer
International Immunopharmacology, 2014
There are more than 4000 natural and synthetic molecules structurally and/or functionally related to vitamin A. Retinoids are a class of these compounds that are structurally associated to vitamin A. The retinoids have a wide spectrum of functions. Retinoic acid, which is the active metabolite of retinol, regulates a wide range of biological processes including development, differentiation, proliferation and apoptosis. It suppresses carcinogenesis in tumorigenic animal models for the skin, oral, lung, breast, bladder, ovarian and prostate. It is important how major retinoids may act in cancer treatment or prevention. The reports have indicated that lower levels of vitamin A in humans may be associated with relative type 1 cytokine dominance and a higher proportion of NK cells. In addition, very low vitamin A levels would be undesirable explaining the essential role of vitamin A in epithelial and general cell maturation and function. However, the cytokine shifts associated with moderately low levels of vitamin A may be in some ways beneficial in an environment where HIV infection, M. tuberculosis infection, or other type 1 infections are highly prevalent and/or when acquired immunity is cooperated. In this review, we intend to describe the biochemical and immunological functions of retinoids against cancer.
Cancer, 1980
The effects of various retinoids on the proliferative capacities and on the synthesis of DNA, RNA, and protein have been investigated in MCF-7 mammary carcinoma cells in culture. Of the various retinoids tested, retinoic acid revealed maximum activity in inhibiting cell proliferation and thymidine incorporation. The degree of inhibition of cell proliferation by the various retinoids paralleled their capacity to inhibit thymidine incorporation, suggesting suppression of DNA synthesis as a primary cause of restriction of cell growth by these compounds. Two nonepithelial human cell lines were tested for sensitivity to retinoids, and showed diminished responses compared with MCF-7 cells. This suggests a correlation between the ability of retinoids to exert control of differentiation and cell proliferation for a given cell type. Reversibility of the effect of retinoid treatment, high cell viability, and lack of retinoidinduced lysosomal enzyme release, as shown in our studies, indicate that cytotoxicity may be excluded as a cause of decreased cell proliferation and inhibition of thymidine incorporation by retinoids. Cancer 46:2203-2209, 1980. ETINOIDS ARE KNOWN to regulate the differ-R entiation of normal epithelial tissue.'.""."' There have been numerous studies of the prophylactic effects of retinoids on epithelial tumors such as chemically induced tumors of mammary glands,12 skin,' urinary bladder,:'2 and prostate. l 5 Retinoids have also been shown to enhance the antitumor effects of x-rays and chemotherapeutic agents.'.".' The effects of retinoids on cultured tumor cells have been investigated. Dion et u/.$I showed that retinoic acid restored density-dependent inhibition of growth in mouse L-929 cells. Various investigators have examined the inhibitory effects of retinoic acid and retinyl acetate on untransformed and transformed cells in
Cancer research, 1988
We have examined the effects of dietary retinoids upon the growth and differentiation of seven embryonal carcinoma lines in mice. The control diet contained 4000 IU/mg retinyl palmitate; the other diets contained 2 x 10(5) IU/mg retinyl palmitate, 50 mg/kg all-trans-retinoic acid (RA), 100 mg/kg RA, and no retinoid. The RA-containing diets had little influence on tumor latency or incidence but did suppress growth of many of the tumors. Decreased tumor mass was, in most but not all instances, accompanied by an increased proportion of differentiated cells. Increased differentiation was most commonly quantitative rather than qualitative; i.e., there was a larger proportion of the same types of differentiated cells seen in tumors from the control diet group rather than an increase in the spectrum of cell types observed. Notably, tumors from two differentiation-defective embryonal carcinoma lines were refractory to both the differentiation-inducing and growth-suppressing properties of di...
High concentrations of retinoids induce differentiation and late apoptosis
Cancer Biology & Therapy, 2005
Background: Our previous investigations showed that retinoids, at specific concentrations, can inhibit cell proliferation. In this investigation, we hypothesize that high concentrations of retinoids can induce phenotypic changes (differentiation) and late apoptosis in pancreatic cancer cells in vitro.