Discovery of gamma-mangostin from Garcinia mangostana as a potent and selective natural SIRT2 inhibitor

被引：24

作者：

Yeong, Keng Yoon ^{[1
]}

Khaw, Kooi Yeong ^{[2
,3
]}

Takahashi, Yukari ^{[4
]}

Itoh, Yukihiro ^{[4
]}

Murugaiyah, Vikneswaran ^{[3
]}

Suzuki, Takayoshi ^{[4
,5
,6
]}

机构：

[1] Monash Univ, Sch Sci, Malaysia Campus,Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia

[2] Monash Univ, Sch Pharm, Malaysia Campus,Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia

[3] Univ Sains Malaysia, Sch Pharmaceut Sci, Discipline Pharmacol, Minden 11800, Penang, Malaysia

[4] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Sakyo Ku, 1-5 Shimogamohangi Cho, Kyoto 6060823, Japan

[5] Osaka Univ, Inst Sci & Ind Res, Suita, Osaka, Japan

[6] Japan Sci & Technol Agcy JST, CREST, 4-1-8 Honcho Kawaguchi, Kawaguchi, Saitama 3320012, Japan

来源：

BIOORGANIC CHEMISTRY | 2020年 / 94卷

关键词：

Mangostin; Sirtuin; Antitumor; Breast cancer; Alzheimer's disease; ALPHA-MANGOSTIN; PRENYLATED XANTHONES; SIRTUINS; PROTEIN; ACTIVATION; CANCER;

D O I：

10.1016/j.bioorg.2019.103403

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Studies have suggested that sirtuin inhibition may have beneficial effects on several age-related diseases such as neurodegenerative disorders and cancer. Garcinia mangostana is a well-known tropical plant found mostly in South East Asia with several positive health effects. Some of its phytochemicals such as alpha-mangostin was found to be able to modulate sirtuin activity in mice and was implicated with inflammation, diabetes and obesity. However, comprehensive studies on sirtuin activity by the prenylated xanthones extracted from Garcinia mangostana have yet to be reported. The present study led to the discovery and identification of gamma-mangostin as a potent and selective SIRT2 inhibitor. It was demonstrated that gamma-mangostin was able to increase the alpha-tubulin acetylation in MDA-MD-231 and MCF-7 breast cancer cells. It was also found to possess potent antiproliferative activity against both cell lines. In addition, it was able to induce neurite outgrowth in the N2a cells.

引用

页数：6

共 42 条

[1] Sirtuin 2 Inhibition Improves Cognitive Performance and Acts on Amyloid-β Protein Precursor Processing in Two Alzheimer's Disease Mouse Models [J].