Zerumbone reduces proliferation of HCT116 colon cancer cells by inhibition of TNF-alpha.

Zerumbone is a known anti-cancer herbal compound. However, the actual protein target is not fully understood or known. This investigation focus on the association of zerumbone in HCT116 colon cancer cell proliferation and its link with TNF-alpha. The study shows that with the increasing concentration of zerumbone, there was a reduction of HCT116 cells proliferation based on the cell line study and hence higher TNF-alpha inhibition based on the TNF-alpha assay. The study also emphasizes on the computational aspect by investigating the molecular docking analysis of zerumbone against TNF-alpha. The docked complex was further validated using molecular dynamics simulation studies. The docking analysis observed that alpha-beta unsaturated carbonyl scaffold is an important moiety for the anti-cancer activity of zerumbone. Furthermore, the DFT analysis also confirms the reactivity nature of zerumbone based on the frontier molecular orbital analysis.

Topical (+)-catechin emulsified gel prevents DMBA/TPA-induced squamous cell carcinoma of the skin by modulating antioxidants and inflammatory biomarkers in BALB/c mice.

An emulsified gel of (+)-catechin was developed and evaluated topically against 7,12-dimethylbenz(a)anthracene-induced and 12-O-tetradecanoylphorbol-13-acetate-promoted (DMBA-induced and TPA-promoted) squamous cell carcinoma of the skin in BALB/c mice. The biological evaluation outcome indicated that the (+)-catechin emulsified gel increased the activity of oxidative stress biomarkers glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx), whereas it decreased the level of malondialdehyde (MDA). The mechanistic study showed that genes implicated in the inflammation and cancer, such as cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-κB), and inducible nitric-oxide synthase (iNOS), were down-regulated by (+)-catechin emulsified gel while inhibiting an inflammatory mediator prostaglandin E2 (PGE2). The (+)-catechin emulsified gel further suppressed the activity of pro-inflammatory cytokines, viz. tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6). The in vitro permeation study revealed that release of (+)-catechin from an emulsified gel base reached a steady state after 6 h, while pH of the entire emulsified gel was found to be between 6.2 and 6.5 that falls well within the normal pH range of the skin.

Novel dual inhibitors of nuclear factor-kappa B (NF-κB) and cyclooxygenase- 2 (COX-2): synthesis, in vitro anticancer activity and stability studies of lantadene-non steroidal anti-inflammatory drug (NSAID) conjugates.

The activation of transcription factors nuclear factor-kappa B (NF-κ B) and cyclooxygenase-2 (COX-2) is critical in cancer; they act synergistically in promoting tumor growth, survival, and resistance to chemotherapy. Thus, combined targeting of NF-κ B and COX-2 present an opportunity for synergistic anticancer efficacy. The ester prodrugs of pentacyclic triterpenoids reduced lantadene A (3), B (4), and its congener 22ß-hydroxyoleanonic acid (5) with various non steroidal anti-inflammatory drugs (NSAIDs) present a novel approach. The ester prodrugs of 3 and 4 with diclofenac showed promising dual inhibition of NF-κ B and COX-2. The lead prodrugs 14 and 15 exhibited inhibition of inhibitor of nuclear factor-kappa B kinaseß (IKKß) in the single-digit micromolar range and at the same time, prodrugs 14 and 15 showed marked cytotoxicity against A549 lung cancer cell line with IC(50s) 0.15 and 0.42 µM, respectively. The prodrugs 14 and 15 exhibited stability in the acidic pH and were hydrolyzed readily in the human blood plasma to release the active parent moieties. Thus, we have synthesized novel hybrid compounds to target both NF-κ B and COX-2 via a prodrug approach, leading to promising anticancer candidates.