Brtko J, Thalhamer J
Institute of Experimental Endocrinology, Slovak Acacemy of Sciences, Bratislava, Slovak Republic.
Curr Pharm Des. 2003;9(25):2067-77. doi: 10.2174/1381612033454144.
Vitamin A and its biologically active derivatives are involved in a complex arrangements of physiological and developmental responses in many tissue of higher vertebrates. Retinoids are natural and synthetic compounds related to retinoic acid that act through interaction with two basic types of nuclear receptors: retinoic acid receptors (RAR alpha, RARbeta and RARgamma) and retinoid X receptors (RXRalpha, RXRbeta and RXRgamma) as retinoid-inducible transcription factors. Thus, the retinoid receptors are considered to be ligand-activated, DNA-binding, trans-acting, transcription-modulating proteins involved in a general molecular mechanism responsible for transcriptional responses in target genes. They exert both beneficial and detrimental activity; they have tumor-suppressive activity but on the other hand they are teratogenic. Retinoids inhibit carcinogenesis, suppress premalignant epithelial lesions and tumor growth and invasion in a variety of tissues. Natural and synthetic retinoids have therapeutical effects due to their antiproliferative and apoptosis-inducing effects. They are known to cause redifferentiation or to prevent further dedifferentiation of various neoplastic tissues. A number of novel chemical compounds, receptor selective retinoids and rexinoids, have been synthesized up to now and tested both in vitro and in vivo, using animal models against different cancer cells. In spite of that progress, there is still an urgent call for novel synthetic retinoids and rexinoids with greater retinoid receptor selectivity, reasonable chemotherapeutic or chemopreventive effects and reduced toxicity and side effects. This article summarizes selected effects of biologically active natural or synthetic retinoids and rexinoids, acting through their cognate nuclear receptors, and their use in chemotherapy and chemoprevention of various types of cancer.
维生素A及其生物活性衍生物参与高等脊椎动物许多组织中复杂的生理和发育反应。类视黄醇是与视黄酸相关的天然和合成化合物，它们通过与两种基本类型的核受体相互作用发挥作用：视黄酸受体（RARα、RARβ和RARγ）和类视黄醇X受体（RXRα、RXRβ和RXRγ），作为类视黄醇诱导型转录因子。因此，类视黄醇受体被认为是配体激活、DNA结合、反式作用、转录调节蛋白，参与负责靶基因转录反应的一般分子机制。它们既具有有益活性，也具有有害活性；它们具有肿瘤抑制活性，但另一方面它们具有致畸性。类视黄醇抑制致癌作用，抑制各种组织中的癌前上皮病变以及肿瘤生长和侵袭。天然和合成类视黄醇由于其抗增殖和诱导凋亡的作用而具有治疗效果。已知它们会导致各种肿瘤组织重新分化或防止其进一步去分化。到目前为止，已经合成了许多新型化合物、受体选择性类视黄醇和视黄酸X受体激动剂，并使用动物模型针对不同癌细胞进行了体外和体内测试。尽管取得了这些进展，但仍迫切需要具有更高类视黄醇受体选择性、合理化疗或化学预防效果以及更低毒性和副作用的新型合成类视黄醇和视黄酸X受体激动剂。本文总结了通过其同源核受体发挥作用的生物活性天然或合成类视黄醇和视黄酸X受体激动剂的选定作用，以及它们在各种癌症化疗和化学预防中的应用。
