S-Nitroso-N-acetylcysteine inhibits proliferation and survival of multiple MM cells. It acts by the S-nitrosylation-dependent inhibition of STAT3 and NF-κB.
The nuclear factor-κB (NF-κB) regulates the expression of numerous genes involved in immunity and inflammation, cellular stress responses, growth, and apoptosis. Resveratrol, a polyphenolic trans-stilbene, is a known inhibitor of the activation of NF-κB and exhibits activity against a wide variety of cancer cells. CAY10512 is a substituted trans-stilbene analog of resveratrol that is 100-fold more potent as measured by antioxidant activity. The IC50 value for inhibition of TNFα-induced activation of NF-κB by CAY10512 is 0.15 μM compared to 20 μM by resveratrol.
C18 Phytoceramide (t18:0 18:0) (Cer(t18:0 18:0)) is a bioactive sphingolipid found in S. cerevisiae, wheat grains, and the stratum corneum layer of mammalian epidermis. Cer(t18:0 18:0) is composed of a phytosphingosine backbone amine-linked to a C18 fatty acid chain. Cer(t18:0 18:0) has a role in regulation of apoptosis, cell differentiation, proliferation of smooth muscle cells, and inhibition of the mitochondrial respiratory chain. It also inhibits expression of the allergic cytokines IL-4, TNF-α, and transcription factors c-Jun and NF-κB in histone-stimulated murine skin tissue. Formulations containing cer(t18:0 18:0) have been used used in cosmetics as a skin protectants as they reduce water loss to prevent epidermal dehydration and irritation.
Potent inhibitor of NF-κB activation (IC50 = 85 nM); decreases IκBα phosphorylation. Attenuates LPS-induced nitric oxide production and expression of TNF-α, IL-6 and MCP. Suppresses proliferation of HeLa and HCT116 cells. Anti-inflammatory and antitumor. Hu et al (2007) Regulation of c-Src nonreceptor tyrosine kinase activity by bengamide A through inhibition of methionine aminopeptidases. Chem.Biol. 14 764 PMID:17656313 |Johnson et al (2012) Myxobacteria versus sponge-derived alkaloids: the bengamide family identified as potent immune modulating agents by scrutiny of LC-MS ELSD libraries. Bioorg.Med.Chem. 20 4348 PMID:22705020 |Kinder et al (2001) Synthesis and antitumor activity of ester-modified analogues of bengamide B. J.Med.Chem. 44 3692 PMID:11606134