Phoyunnanin E

Phoyunnanin E Induces Apoptosis of Non-small Cell Lung Cancer Cells via p53 Activation and Down-regulation of Survivin.[Pubmed:30396948]

Anticancer Res. 2018 Nov;38(11):6281-6290.

BACKGROUND/AIM: Lung cancer is by far the most common cause of cancer mortality, accounting for nearly 20% of all global cancer deaths. Therefore, potent and effective compounds for treatment of this cancer type are essential. Phoyunnanin E, isolated from Dendrobium venustum (Orchidaceae), has promising pharmacological activities; however, it is unknown if Phoyunnanin E affects apoptosis of lung cancer cells. MATERIALS AND METHODS: The apoptosis-inducing activity of Phoyunnanin E on H460 lung cancer cells was investigated by Hoechst 33342, and annexin V-fluorescein isothiocyanate/propidium iodide staining. The underlying mechanism was determined via monitoring apoptosis-regulatory proteins by western blot analysis. The apoptotic effect of the compound was confirmed in H23 lung cancer cells. RESULTS: Phoyunnanin E significantly induced apoptotic cell death of H460 lung cancer cells, as indicated by condensed and fragmented nuclei with the activation of caspase-3 and -9 and poly (ADP-ribose) polymerase cleavage. Phoyunnanin E mediated apoptosis via a p53-dependent pathway by increasing the accumulation of cellular p53 protein. As a consequence, anti-apoptotic proteins including induced myeloid leukemia cell differentiation protein (MCL1) and B-cell lymphoma 2 (BCL2) were found to be significantly depleted, while pro-apoptotic BCL-2-associated X protein (BAX) protein was up-regulated. Furthermore, it was found that expression of an inhibitor of apoptosis, survivin, markedly reduced in response to Phoyunnanin E treatment. The apoptosis-inducting effect was also found in Phoyunnanin E-treated H23 lung cancer cells. CONCLUSION: These results indicate the promising effect of Phoyunnanin E in induction of apoptosis, that may be useful for the development of novel anticancer agents.

Phoyunnanin E inhibits migration of non-small cell lung cancer cells via suppression of epithelial-to-mesenchymal transition and integrin alphav and integrin beta3.[Pubmed:29284478]

BMC Complement Altern Med. 2017 Dec 29;17(1):553.

BACKGROUND: The conversion of the epithelial phenotype of cancer cells into cells with a mesenchymal phenotype-so-called epithelial-mesenchymal transition (EMT)-has been shown to enhance the capacity of the cells to disseminate throughout the body. EMT is therefore becoming a potential target for anti-cancer drug discovery. Here, we showed that Phoyunnanin E, a compound isolated from Dendrobium venustum, possesses anti-migration activity and addressed its mechanism of action. METHODS: The cytotoxic and proliferative effects of Phoyunnanin E on human non-small cell lung cancer-derived H460, H292, and A549 cells and human keratinocyte HaCaT cells were investigated by MTT assay. The effect of Phoyunnanin E on EMT was evaluated by determining the colony formation and EMT markers. The migration and invasion of H460, H292, A549 and HaCaT cells was evaluated by wound healing assay and transwell invasion assay, respectively. EMT markers, integrins and migration-associated proteins were examined by western blot analysis. RESULTS: Phoyunnanin E at the concentrations of 5 and 10 muM, which are non-toxic to H460, H292, A549 and HaCaT cells showed good potential to inhibit the migratory activity of three types of human lung cancer cells. The anti-migration effect of Phoyunnanin E was shown to relate to the suppressed EMT phenotypes, including growth in anchorage-independent condition, cell motility, and EMT-specific protein markers (N-cadherin, vimentin, slug, and snail). In addition to EMT suppression, we found that Phoyunnanin E treatment with 5 and 10 muM could decrease the cellular level of integrin alphav and integrin beta3, these integrins are frequently up-regulated in highly metastatic tumor cells. We further characterized the regulatory proteins in cell migration and found that the cells treated with Phoyunnanin E exhibited a significantly lower level of phosphorylated focal adhesion kinase (p-FAK) and phosphorylated ATP-dependent tyrosine kinase (p-AKT), and their downstream effectors (including Ras-related C3 botulinum (Rac-GTP); Cell division cycle 42 (Cdc42); and Ras homolog gene family, member A (Rho-GTP)) in comparison to those of the non-treated control. CONCLUSIONS: We have determined for the first time that Phoyunnanin E could inhibit the motility of lung cancer cells via the suppression of EMT and metastasis-related integrins. This new information could support further development of this compound for anti-metastasis approaches.

Chemical constituents of Dendrobium venustum and their antimalarial and anti-herpetic properties.[Pubmed:25115090]

Nat Prod Commun. 2014 Jun;9(6):825-7.

A MeOH extract from the whole plant Dendrobium venustum exhibited significant antimalarial and anti-herpetic activities. Bioassay-guided isolation of the plant extract resulted in the isolation of seven known phenolic compounds. Densiflorol B (3) and Phoyunnanin E (6) showed the strongest antimalarial activity and a high selectivity index, whereas gigantol (2), batatasin III (5) and phoyunnanin C (7) exhibited moderate activity. Compounds 2 and 5 also showed weak activity against the Herpes simplex virus. This study is the first report on the chemical and biological activities of D. venustum.

New stilbenoids from Pholidota yunnanensis and their inhibitory effects on nitric oxide production.[Pubmed:16394543]

Chem Pharm Bull (Tokyo). 2006 Jan;54(1):21-5.

Six new stilbenoids, a (bibenzyldihydrophenanthrene) ether designated phoyunnanin D (1), a bis(dihydrophenanthrene) ether designated Phoyunnanin E (2), and four stilbenes designated phoyunbene A-D (3-6), were isolated from the air-dried whole plant of Pholidota yunnanensis ROLFE. The new compounds were identified as 7-[2-(3-hydroxyphenethyl)-4-hydroxy-6-methoxyphenoxy]-4-hydroxy-2-methoxy-9,10-di hydrophenanthrene (1), 1-[(9,10-dihydro-4-hydroxy-2-methoxy-7-phenanthrenyl)oxy]-4,7-dihydroxy-2-methoxy -9,10-dihydrophenanthrene (2), trans-3,3'-dihydroxy-2',4',5-trimethoxystilbene (3), trans-3,4'-dihydroxy-2',3',5-trimethoxystilbene (4), trans-3,3'-dihydroxy-2',5-dimethoxystilbene (5), and trans-3-hydroxy-2',3',5-trimethoxystilbene (6) based on spectroscopic evidence. Furthermore, the inhibitory effects of compounds 1-6 on nitric oxide production in a murine macrophage-like cell line (RAW 264.7) activated by lipopolysaccharide and interferon-gamma were examined.