Chemopreventive Potential of Ethanolic Extracts of Luobuma Leaves (Apocynum venetum L.) in Androgen Insensitive Prostate Cancer
Journal
Nutrients
Journal Volume
9
Journal Issue
9
Pages
16
Date Issued
2017
Author(s)
S. P. Huang
T. M. Ho
C. W. Yang
Y. J. Chang
J. F. Chen
J. C. Horng
S. L. Hsu
M. Y. Liao
L. C. Wu
Abstract
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. ? 2017 by the authors. Licensee MDPI, Basel, Switzerland.
SDGs
Other Subjects
antioxidant; Apocynum venetum extract; beta catenin; caspase 3; caspase 8; cytochrome c; isorhamnetin; kaempferol; lupeol; phytosterol; plant extract; polyphenol; protein bcl 2; protein p53; quercetin; sitosterol; stigamasterol; triterpenoid; unclassified drug; uracil DNA glycosidase; antineoplastic agent; apoptosis regulatory protein; beta catenin; CTNNB1 protein, human; pentacyclic triterpene; plant extract; tumor protein; uracil DNA glycosidase; activity guided fractionation; androgen insensitive prostate cancer; Apocynum; Apocynum venetum; apoptosis; Article; cell cycle; cell proliferation; cell survival; chemoprophylaxis; controlled study; cytotoxicity; DNA damage; DNA repair; down regulation; flow cytometry; fractionation; human; human cell; liquid chromatography-mass spectrometry; luobuma leaf; male; molecular dynamics; MTT assay; nuclear magnetic resonance; PCa cell; prostate cancer; prostate cancer cell line; protein expression; ultra performance liquid chromatography; Western blotting; antagonists and inhibitors; Apocynum; castration resistant prostate cancer; cell cycle G2 phase; chemical structure; chemistry; dietary supplement; ethnopharmacology; isolation and purification; metabolism; pathology; plant leaf; Taiwan; tumor cell line; Wnt signaling; Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Apocynum; Apoptosis Regulatory Proteins; beta Catenin; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dietary Supplements; Ethnopharmacology; G2 Phase; Humans; Male; Molecular Structure; Neoplasm Proteins; Pentacyclic Triterpenes; Plant Extracts; Plant Leaves; Prostatic Neoplasms, Castration-Resistant; Taiwan; Uracil-DNA Glycosidase; Wnt Signaling Pathway
Type
journal article