P27/Kip1 is responsible for magnolol-induced U373 apoptosis in vitro and in Vivo

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Previously, we demonstrated that magnolol, a hydroxylated biphenyl compound isolated from the bark of Magnolia officinalis, at low concentrations (3-10 μM) exerted an antiproliferation effect in colon cancer, hepatoma, and glioblastoma (U373) cell lines through upregulation of the p21/Cip1 protein. Magnolol at a higher concentration of 100 μM, however, induced apoptosis and upregulated p27/Kip1 expression in U373. In the present study, we further studied whether the increased p27/Kip1 expression contributes to the magnolol-induced apoptosis in U373. Our data show that knock-down of p27/Kip1 expression significantly suppressed the magnolol-induced apoptosis, suggesting that p27/Kip1 might play an important role in the regulation of magnolol-induced apoptosis. This notion was further supported by demonstrating that magnolol induced an increase of the caspase activity in U373 in vitro and in vivo, and these effects were abolished by pretransfection of the cell with p27/Kip1 siRNA. To delineate the possible signaling pathways involved in the magnolol-induced increases of p27/Kip1 expression and apoptosis, we found that magnolol (100 μM) increased the levels of phosphorylated cSrc (p-cSrc), p-ERK, p-p38 MAP kinase (p-p38 MAPK), and p-AKT but not p-JNK in U373. Moreover, pretreatment of U373 with a cSrc inhibitor (PP2), a PI3K inhibitor (LY294002), an ERK inhibitor (PD98059), or a p38 MAPK inhibitor (SB203580) but not a JNK inhibitor (SP600125) significantly reduced the magnolol-induced increases of p27/Kip1 protein levels and apoptosis. Taken together, our data suggest that magnolol at a higher concentration of 100 μM induced apopotosis in U373 cells through cSrc-mediated upregulation of p27/Kip1.

Original languageEnglish
Pages (from-to)2811-2819
Number of pages9
JournalJournal of Agricultural and Food Chemistry
Volume61
Issue number11
DOIs
Publication statusPublished - Mar 20 2013
Externally publishedYes

Fingerprint

apoptosis
Apoptosis
mitogen-activated protein kinase
p38 Mitogen-Activated Protein Kinases
Biphenyl Compounds
Up-Regulation
Magnolia
magnolol
In Vitro Techniques
Cyclin-Dependent Kinase Inhibitor p27
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
caspases
phosphatidylinositol 3-kinase
hepatoma
Glioblastoma
Caspases
small interfering RNA
colorectal neoplasms
Phosphatidylinositol 3-Kinases
Colonic Neoplasms

Keywords

  • apoptosis
  • Magnolol
  • P27/Kip1
  • siRNA
  • U373

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Chemistry(all)

Cite this

P27/Kip1 is responsible for magnolol-induced U373 apoptosis in vitro and in Vivo. / Chen, Li Ching; Lee, Wen Sen.

In: Journal of Agricultural and Food Chemistry, Vol. 61, No. 11, 20.03.2013, p. 2811-2819.

Research output: Contribution to journalArticle

@article{67b214c88a0448f6a90a104bef765e72,
title = "P27/Kip1 is responsible for magnolol-induced U373 apoptosis in vitro and in Vivo",
abstract = "Previously, we demonstrated that magnolol, a hydroxylated biphenyl compound isolated from the bark of Magnolia officinalis, at low concentrations (3-10 μM) exerted an antiproliferation effect in colon cancer, hepatoma, and glioblastoma (U373) cell lines through upregulation of the p21/Cip1 protein. Magnolol at a higher concentration of 100 μM, however, induced apoptosis and upregulated p27/Kip1 expression in U373. In the present study, we further studied whether the increased p27/Kip1 expression contributes to the magnolol-induced apoptosis in U373. Our data show that knock-down of p27/Kip1 expression significantly suppressed the magnolol-induced apoptosis, suggesting that p27/Kip1 might play an important role in the regulation of magnolol-induced apoptosis. This notion was further supported by demonstrating that magnolol induced an increase of the caspase activity in U373 in vitro and in vivo, and these effects were abolished by pretransfection of the cell with p27/Kip1 siRNA. To delineate the possible signaling pathways involved in the magnolol-induced increases of p27/Kip1 expression and apoptosis, we found that magnolol (100 μM) increased the levels of phosphorylated cSrc (p-cSrc), p-ERK, p-p38 MAP kinase (p-p38 MAPK), and p-AKT but not p-JNK in U373. Moreover, pretreatment of U373 with a cSrc inhibitor (PP2), a PI3K inhibitor (LY294002), an ERK inhibitor (PD98059), or a p38 MAPK inhibitor (SB203580) but not a JNK inhibitor (SP600125) significantly reduced the magnolol-induced increases of p27/Kip1 protein levels and apoptosis. Taken together, our data suggest that magnolol at a higher concentration of 100 μM induced apopotosis in U373 cells through cSrc-mediated upregulation of p27/Kip1.",
keywords = "apoptosis, Magnolol, P27/Kip1, siRNA, U373",
author = "Chen, {Li Ching} and Lee, {Wen Sen}",
year = "2013",
month = "3",
day = "20",
doi = "10.1021/jf400542m",
language = "English",
volume = "61",
pages = "2811--2819",
journal = "Journal of Agricultural and Food Chemistry",
issn = "0021-8561",
publisher = "American Chemical Society",
number = "11",

}

TY - JOUR

T1 - P27/Kip1 is responsible for magnolol-induced U373 apoptosis in vitro and in Vivo

AU - Chen, Li Ching

AU - Lee, Wen Sen

PY - 2013/3/20

Y1 - 2013/3/20

N2 - Previously, we demonstrated that magnolol, a hydroxylated biphenyl compound isolated from the bark of Magnolia officinalis, at low concentrations (3-10 μM) exerted an antiproliferation effect in colon cancer, hepatoma, and glioblastoma (U373) cell lines through upregulation of the p21/Cip1 protein. Magnolol at a higher concentration of 100 μM, however, induced apoptosis and upregulated p27/Kip1 expression in U373. In the present study, we further studied whether the increased p27/Kip1 expression contributes to the magnolol-induced apoptosis in U373. Our data show that knock-down of p27/Kip1 expression significantly suppressed the magnolol-induced apoptosis, suggesting that p27/Kip1 might play an important role in the regulation of magnolol-induced apoptosis. This notion was further supported by demonstrating that magnolol induced an increase of the caspase activity in U373 in vitro and in vivo, and these effects were abolished by pretransfection of the cell with p27/Kip1 siRNA. To delineate the possible signaling pathways involved in the magnolol-induced increases of p27/Kip1 expression and apoptosis, we found that magnolol (100 μM) increased the levels of phosphorylated cSrc (p-cSrc), p-ERK, p-p38 MAP kinase (p-p38 MAPK), and p-AKT but not p-JNK in U373. Moreover, pretreatment of U373 with a cSrc inhibitor (PP2), a PI3K inhibitor (LY294002), an ERK inhibitor (PD98059), or a p38 MAPK inhibitor (SB203580) but not a JNK inhibitor (SP600125) significantly reduced the magnolol-induced increases of p27/Kip1 protein levels and apoptosis. Taken together, our data suggest that magnolol at a higher concentration of 100 μM induced apopotosis in U373 cells through cSrc-mediated upregulation of p27/Kip1.

AB - Previously, we demonstrated that magnolol, a hydroxylated biphenyl compound isolated from the bark of Magnolia officinalis, at low concentrations (3-10 μM) exerted an antiproliferation effect in colon cancer, hepatoma, and glioblastoma (U373) cell lines through upregulation of the p21/Cip1 protein. Magnolol at a higher concentration of 100 μM, however, induced apoptosis and upregulated p27/Kip1 expression in U373. In the present study, we further studied whether the increased p27/Kip1 expression contributes to the magnolol-induced apoptosis in U373. Our data show that knock-down of p27/Kip1 expression significantly suppressed the magnolol-induced apoptosis, suggesting that p27/Kip1 might play an important role in the regulation of magnolol-induced apoptosis. This notion was further supported by demonstrating that magnolol induced an increase of the caspase activity in U373 in vitro and in vivo, and these effects were abolished by pretransfection of the cell with p27/Kip1 siRNA. To delineate the possible signaling pathways involved in the magnolol-induced increases of p27/Kip1 expression and apoptosis, we found that magnolol (100 μM) increased the levels of phosphorylated cSrc (p-cSrc), p-ERK, p-p38 MAP kinase (p-p38 MAPK), and p-AKT but not p-JNK in U373. Moreover, pretreatment of U373 with a cSrc inhibitor (PP2), a PI3K inhibitor (LY294002), an ERK inhibitor (PD98059), or a p38 MAPK inhibitor (SB203580) but not a JNK inhibitor (SP600125) significantly reduced the magnolol-induced increases of p27/Kip1 protein levels and apoptosis. Taken together, our data suggest that magnolol at a higher concentration of 100 μM induced apopotosis in U373 cells through cSrc-mediated upregulation of p27/Kip1.

KW - apoptosis

KW - Magnolol

KW - P27/Kip1

KW - siRNA

KW - U373

UR - http://www.scopus.com/inward/record.url?scp=84875469127&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875469127&partnerID=8YFLogxK

U2 - 10.1021/jf400542m

DO - 10.1021/jf400542m

M3 - Article

C2 - 23448150

AN - SCOPUS:84875469127

VL - 61

SP - 2811

EP - 2819

JO - Journal of Agricultural and Food Chemistry

JF - Journal of Agricultural and Food Chemistry

SN - 0021-8561

IS - 11

ER -