Open AccessRole of retinoids in the prevention and treatment of colorectal cancer
Author(s) -
Catherine C. Applegate,
Michelle A. Lane
Publication year - 2015
Publication title -
world journal of gastrointestinal oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 26
ISSN - 1948-5204
DOI - 10.4251/wjgo.v7.i10.184
Subject(s) - cancer research , retinoic acid , cell growth , wnt signaling pathway , retinoid , retinoic acid receptor , signal transduction , protein kinase b , colorectal cancer , medicine , pi3k/akt/mtor pathway , cellular differentiation , biology , cancer , microbiology and biotechnology , cell culture , biochemistry , genetics , gene
Vitamin A and its derivatives, retinoids, have been widely studied for their use as cancer chemotherapeutic agents. With respect to colorectal cancer (CRC), several critical mutations dysregulate pathways implicated in progression and metastasis, resulting in aberrant Wnt/β-catenin signaling, gain-of-function mutations in K-ras and phosphatidylinositol-3-kinase/Akt, cyclooxygenase-2 over-expression, reduction of peroxisome proliferator-activated receptor γ activation, and loss of p53 function. Dysregulation leads to increased cellular proliferation and invasion and decreased cell-cell interaction and differentiation. Retinoids affect these pathways by various mechanisms, many involving retinoic acid receptors (RAR). RAR bind to all-trans-retinoic acid (ATRA) to induce the transcription of genes responsible for cellular differentiation. Although most research concerning the chemotherapeutic efficacy of retinoids focuses on the ability of ATRA to decrease cancer cell proliferation, increase differentiation, or promote apoptosis; as CRC progresses, RAR expression is often lost, rendering treatment of CRCs with ATRA ineffective. Our laboratory focuses on the ability of dietary vitamin A to decrease CRC cell proliferation and invasion via RAR-independent pathways. This review discusses our research and others concerning the ability of retinoids to ameliorate the defective signaling pathways listed above and decrease tumor cell proliferation and invasion through both RAR-dependent and RAR-independent mechanisms.