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Notes:
Volume 2, Issue 3 2017
Journal of Medical Oncology and Therapeutics
Dermatologists & Melanoma 2017
August 31-September 01, 2017
Page 63
&
2
nd
Euro-Global Congress on
August 31-September 01, 2017 London, UK
12
th
Global Dermatologists Congress
Melanoma and Skin Diseases
interaction between BRD4 and chromatin in melanoma cells, particular at the MYC promoter. Finally, the complex showed
potent activity against melanoma xenografts in an
in vivo
mouse model. To our knowledge, this is the first report of a Group
9 metal complex inhibiting the PPI of a member of the bromodomain and extraterminal domain (BET) family. We envision
that complex 1a may serve as a useful scaffold for the development of more potent epigenetic agents against cancers such as
melanoma.
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-dopa through an
in vitro
mushroom tyrosinase assay, and all testing samples illustrated slight mushroom tyrosinase inhibitory
properties. Isophilippinolide A exhibited inhibitory effectivenesses against the A375.S2 melanoma cell line in a cell viability
assay at concentrations ranging from 0 to 200 μM for 24 h. Propidium iodide staining and flow cytometry analyses were applied
to assess cell cycle accumulative distribution. It was discovered that isophilippinolide A caused sub-G1 phase accumulation
in positive correlation for apoptosis to inhibit cell growth. Further investigation revealed that isophilippinolide A induced
A375.S2 cells 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) and dermal cells (fibroblasts). Altogether, the results implied C. philippinense compounds could be considered
functional ingredients in cosmetics, foods, and pharmaceutical products, particularly for their anticancer ability on human skin
melanoma cells. Kinetically inert metal complexes have arisen as promising alternatives to existing platinum and ruthenium
chemotherapeutics. Reported herein, to our knowledge, is the first example of a substitutionally inert, Group 9 organometallic
compound as a direct inhibitor of signal transducer and activator of transcription 3 (STAT3) dimerization. From a series of
cyclometalated rhodium(III) and iridium(III) complexes, a rhodium(III) complex emerged as a potent inhibitor of STAT3 that
targeted the SH2 domain and inhibited STAT3 phosphorylation and dimerization. Significantly, the complex exhibited potent
anti-tumor activities in an
in vivo
mouse xenograft model of melanoma. This study demonstrates that rhodium complexes may
be developed as effective STAT3 inhibitors with potent anti-tumor activity.
Biography
Hui-Min David Wang, a Full Professor at Graduate Institute of Biomedical Engineering (National Chung Hsing University), graduated from the Department of
Chemical Engineering, National Cheng Kung University, Tainan, Taiwan. In 2014, he got Ta-You Wu Memorial Award which is the highest price to young scientist of
Ministry of Science and Technology (MOST) in TW. In 2015, he got Young Scholars Biotechnology Invention Award which is the highest price to young scientist of
Taiwan Society of Biochemistry and Molecular Biology (TSBMB) in TW. In 2016, he got the Precious Stone Award in TW.
davidw@dragon.nchu.edu.tw