Author(s): Sheu, MJ (Sheu, Ming-Jyh); Huang, GJ (Huang, Guan-Jhong); Wu, CH (Wu, Chieh-Hsi); Chen, JS (Chen, Jwo-Sheng); Chang, HY (Chang, Heng-Yuan); Chang, SJ (Chang, Shu-Jen); Chung, JG (Chung, Jing-Gung)
Title: Ethanol extract of Dunaliella salina induces cell cycle arrest and apoptosis in A549 human non-small cell lung cancer cells
Source: IN VIVO, 22 (3): 369-378 MAY-JUN 2008 Language: English
Document Type: Article
Author Keywords: Dunaliella salina; beta-carotene; apoptosis; A549; p53; NSCLS
KeyWords Plus: 9-CIS BETA-CAROTENE; ANTIOXIDANT ACTIVITY; IN-VIVO; ASCORBIC- ACID; VITAMIN-E; ACTIVATION; EXPRESSION; BARDAWIL; ALGAE; RATS
Abstract: The ethanol extract of Dunaliella salina (EDS) on proliferation and apoptosis in the A549 human lung cancer cell line and their associated protein expressions were investigated.
After 24 and 48 h treatment, MTT assay showed that 25 mu g/ml of EDS significantly reduced A549 cell proliferation by 25.2% (p<0.05) and 48.3% (p<0.01), respectively. To explore its molecular mechanisms in regulating cell proliferation, we first showed that EDS markedly reduced A549 proliferation via inhibition of BrdU incorporation at 25 mu g/ml by 65.8%
(p<0.001). By cytometric analysis, EDS was found to induce apoptosis and cell cycle arrest in the G0/G1 phase. In the DNA gel electrophoresis assay, EDS (25, 50 and 100 mu g/ml) induced significant apoptosis at 48 h. Annexin V/Propodium iodide double staining
demonstrated that administration of EDS (25 mu g/ml) in 12, 24 and 48 h induces apoptosis of 27.7%, 30.7%, and 38.7%. Western blotting assay demonstrated that EDS significantly increased the expression of cyclin-dependent kinase (CDK) inhibitors p53 and p21 and death- receptor proteins Fas and FasL. Bax expression was also elevated by treatment with EDS.
Our data suggested that EDS could influence the antiproliferative effects and induce cell cycle G0/G1 arrest and apoptosis of A549 lung cancer cells.
Addresses: [Chung, Jing-Gung] China Med Univ, Coll Med, Dept Biol Sci & Technol, Taichung 404, Taiwan; [Sheu, Ming-Jyh] China Med Univ, Dept Physiol, Taichung 404, Taiwan; [Chen, Jwo-Sheng] China Med Univ, Dept Sports Med, Taichung 404, Taiwan;
[Huang, Guan-Jhong; Chang, Heng-Yuan] China Med Univ, Inst Chinese Pharmaceut Sci, Taichung 404, Taiwan; [Sheu, Ming-Jyh; Wu, Chieh-Hsi; Chang, Shu-Jen] China Med Univ, Sch Pharm, Taichung 404, Taiwan; [Chung, Jing-Gung] Asia Univ, Dept Biotechnol, Wufeng, Taichung County, Taiwan
Reprint Address: Chung, JG, China Med Univ, Coll Med, Dept Biol Sci & Technol, 91,Hsueh Shih Rd, Taichung 404, Taiwan.
E-mail Address: [email protected]
Cited References: BENAMOTZ A, 1982, J PHYCOL, V18, P529.
BITTERMAN N, 1994, J APPL PHYSIOL, V76, P1073.
BODZIOCH M, 2005, NUTR CANCER, V51, P226.
BOHM F, 1997, J AM CHEM SOC, V119, P621.
BOHM F, 1998, FEBS LETT, V436, P387.
FUJII Y, 1993, ANTICANCER RES, V13, P389.
GROSS A, 1999, GENE DEV, V13, P1899.
HERRERO M, 2006, J AGR FOOD CHEM, V54, P5597, DOI 10.1021/jf060546q.
HIEBER AD, 2000, NUTR CANCER, V37, P234.
HOSOTANI K, 2005, INT J VITAM NUTR RES, V75, P227, DOI 10.1024/0300-9831.75.4.227.
KIM Y, 2006, CARCINOGENESIS, V27, P1410, DOI 10.1093/carcin/bgi340.
LAI BT, 1993, ZHONGHUA ZHONG LIU Z, V15, P351.
LEVIN G, 1994, FREE RADICAL BIO MED, V17, P77.
LEVIN G, 1997, NUTR CANCER, V27, P293.
LIN LM, 2005, WORLD J GASTROENTERO, V11, P5633.
MAY P, 1999, ONCOGENE, V18, P7621.
MIYASHITA T, 1995, CELL, V80, P293.
MOKADY S, 1989, FOOD CHEM TOXICOL, V4, P221.
MOSSMANN T, 1983, J IMMUNOL METHODS, V65, P55.
MULLER M, 1997, J CLIN INVEST, V99, P403.
MURTHY KNC, 2005, LIFE SCI, V76, P1381, DOI 10.1016/j.lfs.2004.10.015.
NAGASAWA H, 1991, ANTICANCER RES, V11, P713.
NESARETNAM K, 2002, LIPIDS, V37, P557.
NODA A, 1994, EXP CELL RES, V211, P90.
NORSA A, 2006, CANCER BIOTHER RADIO, V21, P68.
POPPEL GV, 1995, AM J CLIN NUTR, V62, S1393.
RAJA R, 2007, MICROBIOL RES, V162, P177, DOI 10.1016/j.micres.2006.03.009.
RAN ZH, 2007, WORLD J GASTROENTERO, V13, P4255.
RE R, 1999, FREE RADICAL BIO MED, V26, P1231.
SABA NF, 2005, CLIN LUNG CANCER, V7, P92.
WEITBERG AB, 1997, J EXP CLIN CANC RES, V16, P11.
WHITE E, 1996, GENE DEV, V10, P1.
XUE LX, 1993, ZHONGHUA YU FANG YI, V27, P350.
YANG ZY, 1995, NAT MED, V1, P1052.
YOON JH, 2002, J HEPATOL, V37, P400.
Cited Reference Count: 35 Times Cited: 1
Publisher: INT INST ANTICANCER RESEARCH
Publisher Address: EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE
ISSN: 0258-851X
29-char Source Abbrev.: IN VIVO ISO Source Abbrev.: In Vivo Source Item Page Count: 10
Subject Category: Medicine, Research & Experimental ISI Document Delivery No.: 312XG