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Subditine, a New Monoterpenoid Indole Alkaloid from Bark of Nauclea subdita (Korth.) Steud. Induces Apoptosis in Human Prostate Cancer Cells
Subditine, a New Monoterpenoid Indole Alkaloid from Bark of Nauclea subdita (Korth.) Steud. Induces Apoptosis in Human Prostate Cancer Cells
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Subditine, a New Monoterpenoid Indole Alkaloid from Bark of Nauclea subdita (Korth.) Steud. Induces Apoptosis in Human Prostate Cancer Cells
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Subditine, a New Monoterpenoid Indole Alkaloid from Bark of Nauclea subdita (Korth.) Steud. Induces Apoptosis in Human Prostate Cancer Cells
Subditine, a New Monoterpenoid Indole Alkaloid from Bark of Nauclea subdita (Korth.) Steud. Induces Apoptosis in Human Prostate Cancer Cells

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Subditine, a New Monoterpenoid Indole Alkaloid from Bark of Nauclea subdita (Korth.) Steud. Induces Apoptosis in Human Prostate Cancer Cells
Subditine, a New Monoterpenoid Indole Alkaloid from Bark of Nauclea subdita (Korth.) Steud. Induces Apoptosis in Human Prostate Cancer Cells
Journal Article

Subditine, a New Monoterpenoid Indole Alkaloid from Bark of Nauclea subdita (Korth.) Steud. Induces Apoptosis in Human Prostate Cancer Cells

2014
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Overview
In this study, a new apoptotic monoterpenoid indole alkaloid, subditine (1), and four known compounds were isolated from the bark of Nauclea subdita. Complete (1)H- and (13)C- NMR data of the new compound were reported. The structures of isolated compounds were elucidated with various spectroscopic methods such as 1D- and 2D- NMR, IR, UV and LCMS. All five compounds were screened for cytotoxic activities on LNCaP and PC-3 human prostate cancer cell-lines. Among the five compounds, the new alkaloid, subditine (1), demonstrated the most potent cell growth inhibition activity and selective against LNCaP with an IC50 of 12.24±0.19 µM and PC-3 with an IC50 of 13.97±0.32 µM, compared to RWPE human normal epithelial cell line (IC50 = 30.48±0.08 µM). Subditine (1) treatment induced apoptosis in LNCaP and PC-3 as evidenced by increased cell permeability, disruption of cytoskeletal structures and increased nuclear fragmentation. In addition, subditine (1) enhanced intracellular reactive oxygen species (ROS) production, as reflected by increased expression of glutathione reductase (GR) to scavenge damaging free radicals in both prostate cancer cell-lines. Excessive ROS could lead to disruption of mitochondrial membrane potential (MMP), release of cytochrome c and subsequent caspase 9, 3/7 activation. Further Western blot analyses showed subditine (1) induced down-regulation of Bcl-2 and Bcl-xl expression, whereas p53 was up-regulated in LNCaP (p53-wild-type), but not in PC-3 (p53-null). Overall, our data demonstrated that the new compound subditine (1) exerts anti-proliferative effect on LNCaP and PC-3 human prostate cancer cells through induction of apoptosis.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject

Alkaloids

/ Alkaloids - chemistry

/ Alkaloids - pharmacology

/ Analysis

/ Apoptosis

/ Apoptosis - drug effects

/ Apoptosis - genetics

/ Bark

/ Bcl-2 protein

/ Bcl-x protein

/ Biology

/ Blotting, Western

/ Cancer

/ Cancer cells

/ Caspase

/ Caspase-9

/ Caspases - metabolism

/ Cell Line, Tumor

/ Cell Nucleus - drug effects

/ Cell Nucleus - metabolism

/ Cell permeability

/ Chemical Sciences

/ Chemistry

/ Chromatography

/ Cytochrome

/ Cytochrome c

/ Cytochromes c - metabolism

/ Cytoskeleton

/ Cytoskeleton - drug effects

/ Cytoskeleton - metabolism

/ Cytotoxicity

/ DNA fragmentation

/ DNA Fragmentation - drug effects

/ Drug Screening Assays, Antitumor

/ Enzyme Activation - drug effects

/ Epithelial cells

/ Free radicals

/ Gene Expression Regulation, Neoplastic - drug effects

/ Glutathione

/ Glutathione reductase

/ Glutathione Reductase - genetics

/ Glutathione Reductase - metabolism

/ Humans

/ Indole Alkaloids - chemistry

/ Indole Alkaloids - pharmacology

/ Indoles

/ Indoles - chemistry

/ Indoles - pharmacology

/ Magnetic Resonance Spectroscopy

/ Male

/ Medicine

/ Membrane potential

/ Membrane Potential, Mitochondrial - drug effects

/ Mitochondria

/ Models, Biological

/ NMR

/ Nuclear magnetic resonance

/ Organic chemistry

/ Oxygen

/ p53 Protein

/ Permeability

/ Pharmacology

/ Pharmacy

/ Plant Bark - chemistry

/ Prostate cancer

/ Prostatic Neoplasms - enzymology

/ Prostatic Neoplasms - genetics

/ Prostatic Neoplasms - pathology

/ Quinolizidines - chemistry

/ Quinolizidines - pharmacology

/ Reactive oxygen species

/ Reactive Oxygen Species - metabolism

/ Solvents

/ Terpenes - chemistry

/ Terpenes - pharmacology

/ Tumor necrosis factor-TNF

/ Tumor proteins