Please use this identifier to cite or link to this item: https://doi.org/10.3390/ijms18051095
Title: Isorhynchophylline, a potent plant alkaloid, induces apoptotic and anti-metastatic effects in human hepatocellular carcinoma cells through the modulation of diverse cell signaling cascades
Authors: Lee, H
Baek, S.H
Lee, J.H
Kim, C
Ko, J.-H
Lee, S.-G
Chinnathambi, A
Alharbi, S.A
Yang, W.M
Um, J.-Y
Sethi, G 
Ahn, K.S
Keywords: caspase 3
caspase 8
caspase 9
chemokine receptor CXCR4
cyclic AMP responsive element binding protein
gelatinase A
gelatinase B
isorhynchophylline
lipocortin 5
mitogen activated protein kinase
nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase
protein kinase B
protein p53
STAT3 protein
stress activated protein kinase
synaptophysin
vasculotropin
antineoplastic agent
indole alkaloid
rhynchophylline
antineoplastic activity
apoptosis
Article
cell cycle assay
cell invasion assay
cell migration
cell proliferation
cell signaling
controlled study
down regulation
enzyme activation
enzyme phosphorylation
genetic transfection
human
human cell
liver cell carcinoma
MTT assay
protein binding
protein expression
signal transduction
TUNEL assay
Uncaria
Western blotting
wound healing assay
apoptosis
cell motion
chemistry
drug effects
Hep-G2 cell line
liver cell carcinoma
liver tumor
metabolism
metastasis
pathology
signal transduction
tumor cell line
Antineoplastic Agents, Phytogenic
Apoptosis
Carcinoma, Hepatocellular
Cell Line, Tumor
Cell Movement
Cell Proliferation
Hep G2 Cells
Humans
Indole Alkaloids
Liver Neoplasms
Neoplasm Metastasis
Signal Transduction
Uncaria
Issue Date: 2017
Publisher: MDPI
Citation: Lee, H, Baek, S.H, Lee, J.H, Kim, C, Ko, J.-H, Lee, S.-G, Chinnathambi, A, Alharbi, S.A, Yang, W.M, Um, J.-Y, Sethi, G, Ahn, K.S (2017). Isorhynchophylline, a potent plant alkaloid, induces apoptotic and anti-metastatic effects in human hepatocellular carcinoma cells through the modulation of diverse cell signaling cascades. International Journal of Molecular Sciences 18 (5) : 1095. ScholarBank@NUS Repository. https://doi.org/10.3390/ijms18051095
Rights: Attribution 4.0 International
Abstract: Isorhynchophylline (Rhy) is an active pharmacological component of Uncaria rhynchophylla that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-etastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.
Source Title: International Journal of Molecular Sciences
URI: https://scholarbank.nus.edu.sg/handle/10635/183525
ISSN: 1661-6596
DOI: 10.3390/ijms18051095
Rights: Attribution 4.0 International
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