Deoxyelephantopin from Elephantopus scaber Inhibits HCT116 Human Colorectal Carcinoma Cell Growth through Apoptosis and Cell Cycle Arrest.

Deoxyelephantopin (DET), one of the major sesquiterpene lactones derived from Elephantopus scaber was reported to possess numerous pharmacological functions. This study aimed to assess the apoptosis inducing effects and cell cycle arrest by DET followed by elucidation of the mechanisms underlying cell death in HCT116 cells. The anticancer activity of DET was evaluated by a MTT assay. Morphological and biochemical changes were detected by Hoescht 33342/PI and Annexin V/PI staining. The results revealed that DET and isodeoxyelephantopin (isoDET) could be isolated from the ethyl acetate fraction of E. scaber leaves via a bioassay-guided approach. DET induced significant dose- and time-dependent growth inhibition of HCT116 cells. Characteristics of apoptosis including nuclear morphological changes and externalization of phosphatidylserine were observed. DET also significantly resulted in the activation of caspase-3 and PARP cleavage. Additionally, DET induced cell cycle arrest at the S phase along with dose-dependent upregulation of p21 and phosphorylated p53 protein expression. DET dose-dependently downregulated cyclin D1, A2, B1, E2, CDK4 and CDK2 protein expression. In conclusion, our data showed that DET induced apoptosis and cell cycle arrest in HCT116 colorectal carcinoma, suggesting that DET has potential as an anticancer agent for colorectal carcinoma.

Kingianins O-Q: Pentacyclic polyketides from Endiandra kingiana as inhibitor of Mcl-1/Bid interaction.

A phytochemical study of the EtOAc-soluble part of the methanolic extract of the bark of Endiandra kingiana led to the isolation of three new pentacyclic kingianins as racemic mixtures, kingianins O-Q (1-3), together with the known kingianins A, F, K, L, M and N (4-9), respectively. The structures of the new kingianins 1-3 were determined by 1D and 2D NMR analysis in combination with HRESIMS experiments. Kingianins A-Q were assayed for Mcl-1 binding affinity. Kingianins G and H were found to be potent inhibitors of Mcl-1/Bid interaction. A structure-activity relationship study showed that potency is very sensitive to the substitution pattern on the pentacyclic core. In addition, in contrast with the binding affinity for Bcl-xL, the levorotatory enantiomers of kingianins G, H and J exhibited similar binding affinities for Mcl-1 than their dextrorotatory counterparts, indicating that the two anti-apoptotic proteins have slightly different binding profiles.

Mitigation of H(2)O(2)-Induced Mitochondrial-Mediated Apoptosis in NG108-15 Cells by Novel Mesuagenin C from Mesua kunstleri (King) Kosterm.

This study was aimed to isolate and evaluate neuroprotective compounds from the hexane extract of the bark of Mesua kunstleri (Clusiaceae) on H(2)O(2)-induced apoptosis in NG108-15 cells. Five 4-phenylcoumarins were isolated by using various chromatographic techniques via neuroprotective activity-guided fractionation and isolation from the active hexane extract. The chemical structures of the isolated compounds were confirmed by NMR spectroscopic data interpretation and comparison with literature values. Cell viability data demonstrated that mesuagenin C 3 significantly increased cell viability. Hoechst 33342/PI staining illustrated mesuagenin C 3 was able to abate the nuclear shrinkage, chromatin condensation and formation of apoptotic bodies. Pretreatment with mesuagenin C 3 reduced total annexin V positive cells and increased the level of intracellular glutathione (GSH). Mesuagenin C 3 attenuated membrane potential (Δψm), reduced Bax/Bcl-2 ratio and inactivated of caspase-3/7 and -9. These results indicated that mesuagenin C 3 could protect NG108-15 cells against H(2)O(2)-induced apoptosis by increasing intracellular GSH level, aggrandizing Δψm, and modulating apoptotic signalling pathway through Bcl-2 family and caspase-3/7 and -9. These findings confirmed the involvement of intrinsic apoptotic pathway in H(2)O(2)-induced apoptosis and suggested that mesuagenin C 3 may have potential therapeutic properties for neurodegenerative diseases.