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

Abstract

Synthetic oleanane triterpenoids and rexinoids are two new classes of multifunctional drugs. They are neither conventional cytotoxic agents, nor are they monofunctional drugs that uniquely target single steps in signal transduction pathways. Synthetic oleanane triterpenoids have profound effects on inflammation and the redox state of cells and tissues, as well as being potent anti-proliferative and pro-apoptotic agents. Rexinoids are ligands for the nuclear receptor transcription factors known as retinoid X receptors. Both classes of agents can prevent and treat cancer in experimental animals. These drugs have unique molecular and cellular mechanisms of action and might prove to be synergistic with standard anti-cancer treatments.

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

“…In transgenic AD mouse models intrahippocampal injections of the lentiviral vector expressing Nrf2 decreased Aβ plaque, reduced learning deficits, and protected against Aβ-induced cell death [158,159]. Synthetic triterpenoids have been demonstrated to induce expression of Nrf2 and to protect against cell death in both in vitro and in vivo experiments [160,161]. Development of strategies that target this Nrf2/antioxidant response element pathway are at an early stage and require substantial translational research.…”

“…MeDi, opposed to the Western diet, is characterized by the abundant consumption of plant foods such as vegetables, fruits, breads, potatoes, legumes, nuts, [160,161] AD = Alzheimer's disease; mTOR = mammalian target of rapamycin; Aβ = β-amyloid; Nrf2 = nuclear response factor 2 and seeds; olive oil as the source of fat; moderate amounts of dairy, fish, poultry, and eggs; low intake of red meats; and wine during normal meals [173,174,195]. The nutrients within the MeDi influence biological mechanisms affecting vascular, antioxidant, and inflammatory pathways [175,176].…”

CDDO-Me, a synthetic triterpenoid, inhibits expression of IL-6 and Stat3 phosphorylation in multi-drug resistant ovarian cancer cells

“…CDDO-Me, also known as RTA-402, NSC713200, is a novel C-28 methyl ester synthetic oleanane triterpenoid. When CDDO-Me applied to macrophages at low concentrations, it demonstrates a variety of anti-inflammatory effects; at higher concentrations the compound inhibits cancer cell growth and proliferation in a wide variety of cell lines [17]. CDDO-Me is consistently more active than the parental compound, CDDO [15].…”

“…CDDO-Me-induced apoptosis is associated with activation of caspase 3 and 8, cytochrome c, SOCS-1, and SHP-1, and inhibition of NF-kB, Cox2, and VEGF. SOCS-1 and SHP-1 have been shown to inhibit Stat3 phosphorylation [17,24,28]. To date, however, the effect of triterpenoids on multidrug resistant ovarian cancer cells is undefined.…”

Ursolic acid in cancer prevention and treatment: Molecular targets, pharmacokinetics and clinical studies

“…To date, $20,000 triterpenoids, including dammarane, ergostane, friedelane, lupane, oleanane, taraxastane, and ursane, have been identified from the various parts of medicinal plants. These emphasize the potential of various plant-derived cyclosqualenoid molecules to be used as anti-inflammatory, anticancer and antimicrobial agents [5]. Among various terpenoids, pentacyclic triterpenoids have been shown from various studies to be having wide ranging anti-inflammatory, chemopreventive, and anticancer activities and have been extensively studied previously [6][7][8][9].…”