Previous studies have shown that alpha-mangostin has cytotoxic potentials by increasing apoptotic and promoting arrest in the cell cycle process in hepatocellular carcinoma in vitro. Prior research has also shown that alpha- mangostin ameliorates alcohol’s toxicity in hepatic stellate cells in vitro; however, whether alpha-mangostin exerts its effect by inducing apoptosis is still unknown. The study was aimed to analyze the apoptotic properties of alpha-mangostin in acetaldehyde-induced hepatic stellate cells in vitro. Immortalized human hepatic stellate (HSC) cells with LX2 cell line were treated with acetaldehyde in the presence or absence of alpha-mangostin (10 and 20 µM). After treatments, cells were harvested, isolated for RNA, and analyzed for mRNA expressions of apoptotic markers: Bax, Bcl-2, caspase-3, and caspase-9 using qRT-PCR. Acetaldehyde treatment caused a significant reduction in the mRNA expressions of Bax and caspase-3 and a slight decrease in the expressions of caspase-9. The addition of alpha-mangostin increased the mRNA expressions of Bax, caspase-9, and caspase-3 significantly. Increased mRNA expressions of Bcl-2 in alpha-mangostin- treated cells were observed. These effects displayed a dose-dependent tendency. Alpha-mangostin demonstrates apoptotic activity in acetaldehyde-induce hepatic stellate cells in a dose-dependent manner.

1.
Chrostek
L.
Liver fibrosis markers in alcoholic liver disease
.
World J Gastroenterol.
2014
;
20
(
25
):
8018
.
2.
Bataller
R
,
Brenner
DA
.
Liver fibrosis
.
J Clin Invest.
2005
Feb 1;
115
(
2
):
209
18
.
3.
Reeves
H L.
Activation of hepatic stellate cells—A key issue in liver fibrosis
.
Front Biosci.
2002
;
7
(
1–3
):
d808
.
4.
Moreira
RK
.
Hepatic stellate cells and liver fibrosis
.
Arch Pathol Lab Med.
2007
;
131
(
11
):
1728
34
.
5.
Elsharkawy
AM
,
Oakley
F
,
Mann
DA
.
The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis
.
Apoptosis.
2005
;
10
(
5
):
927
39
.
6.
Kwak
H-H
,
Kim
I-R
,
Kim
H-J
,
Park
B-S
,
Yu
S-B.
α -Mangostin Induces Apoptosis and Cell Cycle Arrest in Oral Squamous Cell Carcinoma Cell
.
Evid Based Complement Alternat Med.
2016
;
2016
:
1
10
.
7.
Kritsanawong
S
,
Innajak
S
,
Imoto
M
,
Watanapokasin
R.
Antiproliferative and apoptosis induction of α-mangostin in T47D breast cancer cells
.
Int J Oncol.
2016
May;
48
(
5
):
2155
65
.
8.
Lee
C-H
,
Ying
T-H
,
Chiou
H-L
,
Hsieh
S-C
,
Wen
S-H
,
Chou
R-H
, et al. 
Alpha-mangostin induces apoptosis through activation of reactive oxygen species and ASK1/p38 signaling pathway in cervical cancer cells
.
Oncotarget.
2017
Jul 18;
8
(
29
):
47425
39
.
9.
Musumeci
G
,
Castrogiovanni
P
,
Trovato
F
,
Weinberg
A
,
Al-Wasiyah
M
,
Alqahtani
M
, et al. 
Biomarkers of chondrocyte apoptosis and autophagy in osteoarthritis
.
Int J Mol Sci.
2015
Aug 31;
16
(
9
):
20560
75
.
10.
Elmore
S.
Apoptosis: A review of programmed cell death
.
Toxicol Pathol.
2007
Jun;
35
(
4
):
495
516
.
11.
Cai
N
,
Xie
S-J
,
Qiu
D-B
,
Jia
C-C
,
Du
C
,
Liu
W
, et al. 
Potential effects of α-mangostin in the prevention and treatment of hepatocellular carcinoma
.
J Funct Foods.
2016
Oct;
26
:
309
18
.
12.
Lestari
N
,
Louisa
M
,
Soetikno
V
,
Suwana
AG
,
Ramadhan
PA
,
Akmal
T
, et al. 
Alpha mangostin inhibits the proliferation and activation of acetaldehyde induced hepatic stellate cells trough TGF-β and ERK 1/2 pathways
.
J Toxicol.
2018
; Vol
2018
; Article ID 5360496.
13.
Rahmaniah
R
,
Yuyuntia
Y
,
Soetikno
V
,
Arozal
W
,
Antarianto
RD
,
Louisa
M.
Alpha mangostin inhibits hepatic stellate cells activation through TGF-β/Smad and Akt signaling pathways: An in vitro study in LX2
.
Drug Res (Stuttg)
.
2018
Mar;
68
(
3
):
153
8
.
14.
Reed
JC
.
Mechanisms of Apoptosis
.
Am J Pathol.
2000
Nov;
157
(
5
):
1415
30
.
15.
Li
B
,
Dou
QP
.
Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression
.
Proc Natl Acad Sci USA.
2000
Apr 11;
97
(
8
):
3850
5
16.
Pistritto
G
,
Trisciuoglio
D
,
Ceci
C
,
Garufi
A
,
D’Orazi
G.
Apoptosis as anticancer mechaniism: function and dysfunction of its modulators and targeted therapeutic strategies
.
Aging (Albany NY)
.
2016
Mar 27;
8
(
4
):
603
19
.
17.
Pop
C
,
Salvesen
GS
.
Human caspases: Activation, specificity, and regulation
.
J Biol Chem.
2009
Aug 14;
284
(
33
):
21777
81
.
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