Vol. 171, No. 1, 1990 August 31, 1990

BIOCHEMICAL

AND BIOPHYSICAL RESEARCH COMMUNICATIONS Pages 91-96

EFFECTS OF PHORBOL ESTER ON CELL GROWTH INHIBITION BY TRANSFORMING GROWTH FACTOR fil IN HUMAN HEPATOMA CELL LINES Kenji

TAJSAISHI, Sumio KAWATA*, Nobuyuki ITO, Shinji Yasuhiro SHIRAI, and Seiichiro TARUI

Second Department of Internal Medicine, Medical School, Fukushima, Fukushima-ku,

TAMURA,

Osaka University Osaka 553, Japan

Received July 10, 1990 The effects of phorbol ester on cell growth inhibition by transSummary forming growth factor 81 (TGF-81) in human hepatoma cell lines, Mahlavu and PLC/PRF/S, were investigated. TGF-81 (2.5 to 10 PM) alone could not inhibit the growth of Mahlavu cells, whereas in the presence of 12-O-tetradecanoyl phorbol 13-acetate (TPA) at 1 nglml, TGP-/?l could suppress their growth in a dose-dependent manner. The growth of PLC/PRF/S cells could be inhibited by addition of TGF-81 (2.5 to 10 PM) alone in a dose-dependent manner, and this action was not affected by TPA (1 rig/ml). The TGF-81 inhibition induced by TPA in Mahlavu cells could not be cancelled by addition of protein kinase C inhibitor, 1-(S-isoquinolinesulfonyl)-2-methylpiperazine (H7) (10 pM) or staurosporin (1 nM). Thus, TPA could induce TGF-fil inhibition of cell growth in Mahlavu cells which did not respond to TGF-81 alone, and activation of protein kinase C does not seem to be behind this TPA action. @ 1990 Academic Press,

1°C.

Transforming growth factor polypeptide

having a disulfide-linked

weight of 2.5 kDa (l-3). in epithelial tive

cell

cells

We reported

cells.

TGF-fi

However, very little

multifunctional

with a molecular

is a potent cell

(4.5) and is thought to be a likely

growth inhibitor

candidate for a nega-

is known about the mechanisms

by TGF-i3 .

elsewhere a differential

of two humanhepatoma cell inhibited

dimeric structure

In general,

growth regulator.

of growth regulation

strongly

(TGF-fi ) is a biologically

4

lines,

effect

PLC/PRF/S (6) and Mahlavu (7).

the growth of PLC/PRF/5 cells,

The growth inhibitory

effect

of c-myc expression (8). As further

of TGP-81 on the cell growth TGF-81

but not that of Mahlavu

on PLC/PRF/S could exert via suppression examination demonstrated that Mahlavu

* To whom correspondence should be addressed. 0006-2911090 $1.50 91

Copyright 0 1990 by Academic PressJnc. All rights of reproduction in any form reserved.

Vol.

171, No. 1, 1990

cells

possess all

mality

BIOCHEMICAL

types of TGF-81 receptors

in the postreceptor

Phorbol ester, ates the effect

AND BIOPHYSICAL

(g-11).

signal transduction

a potent protein

RESEARCH COMMUNICATIONS

there may be someabnor-

of TGF-81 (12).

kinase C (PKC) activator

(13-15),

of TGF-@ which stimulates anchor-independent

rat kidney fibroblast

(NRK) cells without

potenti-

growth of normal

an increase in TGF-,91 binding (16).

However, there is no evidence concerning the effects

of phorbol ester on

epithelial

study, we investigated

the effects regulation

cell growth inhibition

by TGF-8.

In this

of 12-O-tetradecanoyl-phorbol-13-acetate by TGF-81 in two humanhepatoma cell

(TPA) on cell lines,

growth

Mahlavu and PLC/PRF/S.

Methods TGF-61 was purchased from Takara Biochemicals, Japan, TPA Materials was from Sigma, Staurosporin (17,18) was from Kyowa Medex Co., Japan, and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) (19-22) was from Seikagaku Kogyo Co., Japan. Cosmedium(containing bovine insulin

Effects of phorbol ester on cell growth inhibition by transforming growth factor beta 1 in human hepatoma cell lines.

The effects of phorbol ester on cell growth inhibition by transforming growth factor beta 1 (TGF-beta 1) in human hepatoma cell lines, Mahlavu and PLC...
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