## 4 Role of Triterpenoids in Cancer Prevention
### Role of Triterpenoids in Inflammation
Momordin inhibited the activation of NF-kB as well as AP-1 in receptor activator of NF-kB ligand (RANKL)-induced RAW264.7 cells, in which momordin appeared to target IxB degradation and c-Fos expression, but not MAPK signaling pathways [104]. Saikosaponins are triterpenepe saponins derived from the medicinal plant _Bupleurum falcatum_ L. (Umbelliferae) that have shown various pharmacological and immunomodulatory activities including anti-inflammatory, antibacterial, antiviral and anticancer effects in ACHN, C32, Caco-2, A375, A549, and Huh-7D12 cell lines [170]. Studies demonstrated that saikosaponins not only suppressed the proliferation of human T cells costimulated with OKT3 and CD28 but also inhibited PMA-, PMA/ionomycin-, and concanavalin A-induced mouse T-cell activation _in vitro_. This inhibitory effect of saikosaponins on PMA-induced T-cell activation was associated with the downregulation of NF-kB signaling through the suppression of IKK and Akt activities. Saikosaponins also suppressed both the DNA binding activity and the nuclear translocation of nuclear factor of activated T cells (NF-AT) and AP-1 in the PMA/ionomycin-stimulated T cells. In addition, the cell surface markers like IL-2 receptor (CD25) were also downregulated, and the production of proinflammatory cytokines such as IL-6, TNF-\(\alpha\), and interferon (IFN)-\(\gamma\) was decreased. These results indicate that the NF-kB, NF-AT, and AP-1 (c-Fos) signaling pathways are involved in the T cell inhibition evoked by saikosaponins, demonstrating their potential for treating T cell-mediated autoimmune conditions [123]. Another study showed that saikosaponins have direct involvement in p53-, NF-kB- and Fas/Fas ligand-mediated induction of apoptosis and cell cycle arrest in human hepatoma cell lines. Saikosaponins also inhibited cell survival signaling by enhancing the amount of IxB\(\alpha\) in the cytoplasm and reducing the level and activity of NF-kB in the nucleus, and subsequently attenuated the expression of bcl-xL in HepG2 and HepG3B cells. Saikosaponins therefore decreased cell proliferation and induced apoptosis both in p53-positive HepG2 and p53-negative HepG3B cells [121]. Diosgenin, a steroidal triterpenoid having two pentacyclic rings, is present in _Trigonella foenum graecum_ and other plants and has been shown to suppress inflammation, inhibit proliferation, and induce apoptosis in a variety of tumor cells. Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, IKK activation, and NF-kB-regulated gene expression. Diosgenin suppresses NF-kB through direct DNA binding, activation of IKK, IxB\(\alpha\) phosphorylation, IxB\(\alpha\) degradation, p65 phosphorylation, and p65 nuclear translocation by inhibitingAkt activation. NF-kB-dependent reporter gene expression was also abrogated by diosgenin [64]. Similar activity was found in _Withania somifera_, also known as Indian ginseng, which is widely used in the Ayurvedic system of medicine to treat tumors, inflammation, arthritis, asthma, and hypertension. Chemical investigation of the roots and leaves of this plant has yielded bioactive withanolides, a group of C28-steroidal lactone triterpenoids. _Withania somifera_ inhibits COX enzymes, lipid peroxidation, and proliferation of tumor cells, and it potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis through the suppression of NF-kB activation and NF-kB-regulated gene expression [135]. Ursolic acid is a pentacyclic triterpene compound isolated from many types of medicinal plants and widely present in the human diet. It has been reported to possess a wide range of pharmacological properties and is one of the most promising chemoprevertive agents for cancer. It has been shown to suppress the expression of several genes associated with tumorigenesis. It suppressed NF-kB activation induced by various carcinogens including TNF, PMA, okadaic acid, hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)), and cigarette smoke condensate. Ursolic acid inhibited DNA binding of NF-kB.