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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 62
&
2
nd
Euro-Global Congress on
August 31-September 01, 2017 London, UK
12
th
Global Dermatologists Congress
Melanoma and Skin Diseases
Melanoma & Skin Diseases
Hui-Min David Wang
National Chung Hsing University, Taichung 402, Taiwan
T
his study assessed the use of astaxanthin as an anticancer agent for increasing inhibition to melanoma cells (A375 and
A2058). Wound healing and invasion assays presented that astaxanthin treatment reduced melanoma cell migration
in a dose-dependent manner. The effects on melanoma cell migration were conferred via suppressed expressions of matrix
metalloproteinases 1, 2 and 9. Dichlorofluorescein diacetate assay further showed that astaxanthin treatment reduced
production of cellular reactive oxygen species. Cellular proliferation assay revealed potent dose-dependent inhibiting effects
on melanoma cells. One-dimensional flow cytometric analysis demonstrated that astaxanthin induced cell cycle arrest in G1
phase. Mechanisms of apoptosis were verified by double fluorescence staining with annexin V-fluorescein isothiocyanate and
propidium iodide. The antitumor effects of astaxanthin significantly decreased tumor size in a xenograft model. In summary,
the experimental results showed that astaxanthin has potent
in vivo
and
in vitro
inhibiting effects on melanoma tumor growth
for developing as 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
antioxidative properties, reducing power, DPPH scavenging activity, and metal ion chelating activity. This study compared
these five extracts in terms of their inhibiting effects on three human malignant melanomas: A375, A375.S2, and A2058.
MTT assay presented the notion 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 proteins in all three melanomas. To determine their roles in melanogenesis, this study analyzed
their
in vitro
suppressive effects on mushroomtyrosinase.All extracts except for water revealedmoderate suppressive effects.
None of the extracts affected B16-F10 cells proliferation. EA extract inhibited cellular melanin production whereas DMextract
unexpectedly enhanced cellular pigmentation in B16-F10 cells. Data for modulations of microphthalmia-associated
transcription factor, tyrosinase, tyrosinase-related protein 1 and tyrosinase-related protein 2 showed that EA extract inhibited
protein expression mentioned above whereas DMextract had the opposite effect. Overall, the experiments indicated that the
biofunctional activities of EA extract contained in food and cosmetics protect against oxidation, melanoma, and melanin
production.
Melanoma is the deadliest cancer. We identified 7-hydroxydehydronuciferine (7-HDNF) isolated from the leaves of
Nelumbo nucifera Gaertn cv. Rosa-plena to be a bio-active agent that antagonizes melanoma tumor growth in mice xenograft
model
in vivo
. Cell proliferation assay demonstrated strong anticancer effects of 7-HDNF to exhibit a dose-dependent
behaviour and displayed minor cytotoxicities on normal human skin cells, including epidermal keratinocytes and melanocytes,
and dermal fibroblasts. With acridine orange (AO) staining and flow analysis, we found 7-HDNF induced the formation of
intracellular vacuoles and the augmentation of acidic vesicular organelles (AVO). The apoptotic cell death ratio was measured
via two-dimensional flow cytometry by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double stained
to confirm the cellular membrane asymmetry lost. Onedimensional flow cytometric analysis showed 7-HDNF increased the
cellular arrest in cell cycle at the G2/M phase. Through Western blot examinations, protein expressions were discovered to
verify autophagy and apoptosis response mechanisms sharing the associated pathways. Finally, 7-HDNF presented a high-
quality antimigratory activity in wound-healing assay. Overall, 7-HDNF presented high-quality anticancer bio-functions and
inhibited melanoma tumor growth
in vivo
and
in vitro
.
Bromodomain-containing protein 4 (BRD4) has recently emerged as an attractive epigenetic target for anticancer therapy.
In this study, an iridium(III) complex is reported as the first metal-based, irreversible inhibitor of BRD4. Complex 1a is able
to antagonize the BRD4-acetylated histone protein– protein interaction (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
Hui-Min David Wang, J Med Oncl Ther 2017, 2:3