Chemopreventive Potential of Ethanolic Extracts of Luobuma Leaves (Apocynum venetum L.) in Androgen Insensitive Prostate Cancer

Nutrients

Ning-Sing Shaw¹  Tzu-Ming Ho²  Chih-Wen Yang²  Jie-Fu Chen²  Ya-Ju Chang²  Li-Chen Wu³  Ming-Yuan Liao⁴  Szu-Ping Huang⁵  Ja-an Annie Ho⁵  Jia-Cherng Horng⁵  Shih-Lan Hsu⁶ 

[1] Applied and Translational Nutrition Laboratory, Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan;BioAnalytical Chemistry and Nanobiomedicine Laboratory, Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan;Department of Applied Chemistry, National Chi Nan University, Puli, Nantou 54561, Taiwan;Department of Chemistry, National Chung-Hsin University, Taichung 40227, Taiwan;Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan;Department of Medical Education & Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan;

关键词: composition analysis;    Apocynum venetum L.;    anti-cancer activity;    synergistic therapy;    lupeol;    androgen-insensitive prostate cancer;   

DOI  :  10.3390/nu9090948

来源: DOAJ

【 摘 要 】

Luobuma (Apocynum venetum L. (AVL)) is a popular beverage in Asia and has been reportedly to be associated with the bioactivities such as cardiotonic, diuretic, antioxidative, and antihypertensive. However, its biofunction as chemoprevention activity is seldom addressed. Herein, we aimed to characterize the anti-androgen-insensitive-prostate-cancer (anti-AIPC) bioactive compounds of Luobuma, and to investigate the associated molecular mechanisms. Activity-guided-fractionation (antioxidative activity and cell survivability) of Luobuma ethanolic extracts was performed to isolate and characterize the major bioactive compounds using Ultra Performance Liquid Chromatography (UPLC), Liquid Chromatography-Mass Spectrometry (LC-MS), and Nuclear Magnetic Resonance (NMR). Plant sterols (lupeol, stigamasterol and β-sitosterol) and polyphenolics (isorhamnetin, kaempferol, and quercetin) were identified. Lupeol, a triterpene found in the fraction (F8) eluted by 10% ethyl acetate/90% hexane and accounted for 19.3% (w/w) of F8, inhibited the proliferation of PC3 cells. Both lupeol and F8 induced G2/M arrest, inhibition of β-catenin signaling, regulation of apoptotic signal molecules (cytochrome c, Bcl-2, P53, and caspase 3 and 8), and suppression DNA repair enzyme expression (Uracil-DNA glycosylase (UNG)). To our knowledge, our study is the first report that lupeol inhibited the expression of UNG to elicit the cytotoxicity against androgen-insensitive-prostate-cancer cells. Collectively, Luobuma, which contains several antitumor bioactive compounds, holds the potential to be a dietary chemopreventive agent for prostate cancer.

【 授权许可】

Unknown