Title:Modulation of k-Ras Signaling by Natural Products
VOLUME: 19 ISSUE: 14
Author(s): S.B. Bharate, B. Singh and R.A. Vishwakarma
Affiliation:Medicinal Chemistry Division, Indian Institute of Integrative Medicine, Council of Scientific and Industrial Research (CSIR), Canal Road, Jammu-180001, India.
Keywords:k-Ras, cancer, natural products, farnesyl transferase, isoprenyl cysteine methyl transferase
Abstract:Ras proteins regulate diverse cellular pathways that are important in the growth and spread of malignancies, including cell
proliferation, cell cycle regulation, cell survival, angiogenesis and cell migration. These proteins lack the conventional transmembrane or
hydrophobic domain typical of membrane associated proteins. Being small and hydrophilic in nature, these proteins undergo four-stage
post-translational lipid modifications viz. prenylation, AAX proteolysis, carboxymethylation and palmitoylation for membrane
localization which is important for their function. Therefore, enzymes involved in these modifications viz. farnesyl transferase (FTase),
geranylgeranyl transferase-I (GGTase-I), geranylgeranyl transferase-II (GGTase-II), Ras converting enzyme-1 (Rce-1) and isoprenyl
cysteine methyl transferase (ICMT) are emerging as potential therapeutic targets for the discovery of newer anticancer therapeutics.
Several natural products have shown modulation of these post-translational enzymes. In the present review, natural products isolated
from terrestrial as well as marine sources showing ability to modulate these k-Ras post-translational targets and their promise as potential
anticancer agents have been discussed. A total of 157 natural products with 141 corresponding references have been covered.
