Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer

Top Cited Papers
Publisher Website
Google Scholar
Abstract
Synthetic oleanane triterpenoids are a new class of non-cytotoxic and highly multifunctional drugs that have applications for the prevention and treatment of not only cancer, but also of many other diseases with an inflammatory component. Synthetic oleanane triterpenoids are anti-inflammatory and cytoprotective, induce the differentiation of tumour cells, suppress the growth of tumour cells and are effective agents for the induction of apoptosis in cancer cells that are resistant to conventional chemotherapeutic agents. Synthetic oleanane triterpenoids have been shown to be highly effective in many in vivo models for the prevention and treatment of cancer. These studies include the suppression of tumour growth in immunocompromised mice, as well as the prevention of primary lung cancer induced by a chemical carcinogen. Molecular targets of synthetic oleanane triterpenoids include KEAP1 (the inhibitor of the transcription factor, NRF2), IκB kinase, transforming growth factor-β signalling and signal transducer and activator of transcription (STAT) signalling. The molecular mechanism of action of the triterpenoids is believed to be mediated by Michael addition with active nucleophilic groups on proteins, such as the -SH groups on cysteine residues. Rexinoids are molecules that selectively bind to the nuclear receptors known as retinoid X receptors. These receptors interact heterodimerically with many other members of the nuclear steroid receptor superfamily, and therefore have the ability to modulate the action of many steroid-like hormonal agents. Great advances have been made in the synthesis of new rexinoids. These agents are highly potent, non-cytotoxic and do not have many of the toxic effects associated with classical retinoids, making them safer agents to use in the clinic. Both synthetic oleanane triterpenoids and rexinoids exert their effects through multiple signalling pathways and have the potential to be used synergistically to control the inflammatory process, as well as deregulated growth associated with cancer.