Biography
Biography: Hu-Min David Wang
Abstract
This study assessed the use of astaxanthin as an anticancer agent for increasing inhibition to melanomacells (A375 and A2058). Wound healing and invasion assays presented that astaxanthin treatmentreduced melanoma cell migration in a dose-dependent manner. The effects on melanoma cell migrationwere conferred via suppressed expressionsof matrix metalloproteinases 1, 2 and 9. Dichlorofluoresceindiacetate assay further showed that astaxanthin treatment reduced production of cellular reactiveoxygen species. Cellular proliferation assay revealed potent dose-dependent inhibiting effects onmelanoma cells. One-dimensional flow cytometric analysis demonstrated that astaxanthin induced cellcycle arrest in G1 phase. Mechanisms of apoptosis were verified by double fluorescence staining withannexin V-fluorescein isothiocyanate and propidium iodide. The antitumor effects of astaxanthin significantlydecreased tumor size in a xenograft model. In summary, the experimental results showed thatastaxanthin has potent in vivo and in vitro inhibiting effects on melanoma tumor growth for developingas chemotherapeutic agents.
Equisetum ramosissimum, a genus of Equisetaceae, is a medicinal plant that can be separated into ethyl acetate (EA), dichloromethane (DM), n-hexane (Hex),methanol (MeOH), andwater extracts. EAextract was known to have potent antioxidativeproperties, reducing power, DPPH scavenging activity, and metal ion chelating activity. This study compared these five extractsin terms of their inhibiting effects on three human malignant melanomas: A375, A375.S2, and A2058. MTT assay presented thenotion that both EA and DMextracts inhibited melanoma growth but did not affect the viabilities of normal dermal keratinocytes (HaCaT) or fibroblasts. Western blot analyses showed that both EA and DM extracts induced overexpression of caspase proteinsin all three melanomas. To determine their roles in melanogenesis, this study analyzed their in vitro suppressive effects onmushroomtyrosinase.All extracts except for water revealedmoderate suppressive effects.None of the extracts affected B16-F10 cellsproliferation. EA extract inhibited cellular melanin production whereas DMextract unexpectedly enhanced cellular pigmentationin B16-F10 cells. Data for modulations of microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein 1and tyrosinase-related protein 2 showed that EA extract inhibited protein expression mentioned above whereas DMextract had theopposite effect. Overall, the experiments indicated that the biofunctional activities of EA extract contained in food and cosmeticsprotect against oxidation, melanoma, and melanin production.
Melanoma is the deadliest cancer. We identified 7-hydroxydehydronuciferine (7-HDNF) isolated from the leaves ofNelumbo nucifera Gaertn cv. Rosa-plena to be a bio-active agentthat antagonizes melanoma tumor growth in mice xenograftmodel in vivo. Cell proliferation assay demonstrated stronganticancer effects of 7-HDNF to exhibit a dose-dependentbehaviour and displayed minor cytotoxicities on normal humanskin cells, includingepidermal keratinocytes and melanocytes, and dermal fibroblasts. With acridine orange (AO) staining andflow analysis, we found 7-HDNF induced the formation ofintracellular vacuoles and the augmentation of acidic vesicularorganelles (AVO). The
apoptoticcell death ratio was measuredvia two-dimensional flow cytometry by annexin V-fluoresceinisothiocyanate (FITC)/propidium iodide (PI) double stained toconfirm the cellular membrane asymmetry lost. Onedimensionalflow cytometric analysis showed 7-HDNF increasedthe cellular arrest in cell cycle at the G2/M phase. ThroughWestern blot examinations, protein expressions were discoveredto verify autophagy and apoptosis response mechanisms sharingthe associated pathways. Finally, 7-HDNF presented ahigh-quality antimigratory activity in wound-healing assay. Overall, 7-HDNF presented high-quality anticancerbio-functions and inhibited melanoma tumor growth in vivoand in vitro.
Bromodomain-containing protein 4 (BRD4) has recently emerged as an attractive epigenetic target foranticancer therapy. In this study, an iridium(III) complex is reported as the first metal-based, irreversibleinhibitor of BRD4. Complex 1a is able to antagonize the BRD4-acetylated histone protein–proteininteraction (PPI) in vitro, and to bind BRD4 and down-regulate c-myc oncogenic expression in cellulo.Chromatin immunoprecipitation (ChIP) analysis revealed that 1a could modulate the interactionbetween BRD4 and chromatin in melanoma cells, particular at the MYC promoter. Finally, thecomplex showed potent activity against melanoma xenografts in an in vivo mouse model. To ourknowledge, this is the first report of a Group 9 metal complex inhibiting the PPI of a member of thebromodomain and extraterminal domain (BET) family. We envision that complex 1a may serve as auseful scaffold for the development of more potent epigenetic agents against cancers such asmelanoma.
Three new butanolides, isophilippinolide A, philippinolide A, and philippinolide B, and an amide, cinnaretamine, were isolated from the roots of Cinnamomum philippinense to be identified by spectroscopic analysis. Four isolated compounds were screened to examine their radical-scavenging ability, metal-chelating power, and ferric-reducing antioxidant power assay (FRAP). Cinnaretamine showed powerful antioxidative properties in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and a reducing activity; all compounds presented minor inhibition of metal-chelating capacities. The effects of anti-tyrosinase of C. philippinense constituents were determined by the level of the suppression of hydroxylation that turned from L-tyrosine to L-dopathrough an in vitro mushroom tyrosinase assay, and all testing samples illustrated slight mushroom tyrosinase inhibitoryproperties. Isophilippinolide A exhibited inhibitory effectivenesses against the A375.S2 melanoma cell line in a cell viability assayat concentrations ranging from 0 to 200 μM for 24 h. Propidium iodide staining and flow cytometry analyses were applied toassess cell cycle accumulative distribution. It was discovered that isophilippinolide A caused sub-G1 phase accumulation inpositive correlation for apoptosis to inhibit cell growth. Further investigation revealed that isophilippinolide A induced A375.S2cells with an increase of caspase-dependent apoptotic proteins to trigger correlated pathway mechanisms according to Western
blotting results. Finally, isophilippinolide A displayed only low cytotoxicities to human normal epidermal cells (melanocytes) anddermal cells (fibroblasts). Altogether, the results implied C. philippinense compounds could be considered functional ingredientsin cosmetics, foods, and pharmaceutical products, particularly for their anticancer ability on human skin melanoma cells.
Kinetically inert metal complexes have arisen aspromising alternatives to existing platinum and rutheniumchemotherapeutics. Reported herein, to our knowledge, is thefirst example of a substitutionally inert, Group 9 organometalliccompound as a direct inhibitor of signal transducer andactivator of transcription 3 (STAT3) dimerization. Froma series of cyclometalated rhodium(III) and iridium(III)complexes, a rhodium(III) complex emerged as a potentinhibitor of STAT3 that targeted the SH2 domain and inhibitedSTAT3 phosphorylation and dimerization. Significantly, thecomplex exhibited potent anti-tumor activities in an in vivomouse xenograft model of melanoma. This study demonstratesthat rhodium complexes may be developed as effective STAT3inhibitors with potent anti-tumor activity.