Amelioration of the Cytotoxic Effects of Chemotherapeutic Agents by Grape Seed Proanthocyanidin Extract

被引:29
作者
Joshi, Shantaram S. [1 ,2 ,3 ]
Kuszynski, Charles A. [1 ,2 ,3 ]
Benner, Eric J. [1 ,2 ,3 ]
Bagchi, Manashi [4 ]
Bagchi, Debasis [4 ]
机构
[1] Univ Nebraska, Med Ctr, Dept Cell Biol & Anat, Omaha, NE 68198 USA
[2] Univ Nebraska, Med Ctr, Dept Pathol, Omaha, NE 68198 USA
[3] Univ Nebraska, Med Ctr, Dept Microbiol, Omaha, NE 68198 USA
[4] Creighton Univ, Sch Pharm & Allied Hlth Profess, Omaha, NE 68178 USA
关键词
D O I
10.1089/ars.1999.1.4-563
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Anticancer chemotherapeutic agents are effective in inhibiting growth of cancer cells in vitro and toxicity to normal cells is a major problem. In this study, we assessed the effect of a novel IH636 grape seed proanthocyanidin extract (GSPE) to ameliorate chemotherapy-induced toxic effects in cultured Chang epithelial cells, established from nonmalignant human tissue. These cells were treated in vitro with idarubicin (Ida) (30 nM) or 4-hydroxyperoxycyclophosphamide (4HC) (1 mu g/ml) with or without GSPE (25 mu g/ml). The cells were grown in vitro and the growth rate of the cells was determined using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; thiazolyl blue] assay. Our results showed that GSPE decreased the growth inhibitory and cytotoxic effects of Ida as well as 4HC on Chang epithelial cells in vitro. Because these chemotherapeutic agents are known to induce apoptosis in the target cells, we analyzed the Chang epithelial cells for apoptotic cell population by flow cytometry. There was a significant decrease in the number of cells undergoing apoptosis following treatment with GSPE. W e also found increased expression of the anti-apoptotic protein Bcl-2 in GSPE-treated cells using western blot techniques. Thus, these results indicate that GSPE can be a potential candidate to ameliorate the toxic effects associated with chemotherapeutic agents and one of the mechanisms of action of GSPE includes upregulation of Bcl-2 expression. Antiox. Redox Signal. 1, 563-570.
引用
收藏
页码:563 / 570
页数:8
相关论文
共 29 条
[1]   CHELATING AND FREE-RADICAL SCAVENGING MECHANISMS OF INHIBITORY-ACTION OF RUTIN AND QUERCETIN IN LIPID-PEROXIDATION [J].
AFANASEV, IB ;
DOROZHKO, AI ;
BRODSKII, AV ;
KOSTYUK, VA ;
POTAPOVITCH, AI .
BIOCHEMICAL PHARMACOLOGY, 1989, 38 (11) :1763-1769
[2]   Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice [J].
Bagchi, D ;
Garg, A ;
Krohn, RL ;
Bagchi, M ;
Bagchi, DJ ;
Balmoori, J ;
Stohs, SJ .
GENERAL PHARMACOLOGY, 1998, 30 (05) :771-776
[3]  
Bagchi D, 1997, RES COMMUN MOL PATH, V95, P179
[4]  
Bagchi D, 1998, PHYTOTHER RES, V12, P568, DOI 10.1002/(SICI)1099-1573(199812)12:8&lt
[5]  
568::AID-PTR360&gt
[6]  
3.0.CO
[7]  
2-5
[8]   Acute and chronic stress-induced oxidative gastrointestinal injury in rats, and the protective ability of a novel grape seed proanthocyanidin extract [J].
Bagchi, M ;
Milnes, M ;
Williams, C ;
Balmoori, J ;
Ye, XM ;
Stohs, S ;
Bagchi, D .
NUTRITION RESEARCH, 1999, 19 (08) :1189-1199
[9]   Smokeless tobacco, oxidative stress, apoptosis, and antioxidants in human oral keratinocytes [J].
Bagchi, M ;
Balmoori, J ;
Bagchi, D ;
Ray, SD ;
Kuszynski, C ;
Stohs, SJ .
FREE RADICAL BIOLOGY AND MEDICINE, 1999, 26 (7-8) :992-1000
[10]   Combination of antisense oligonucleotide and low-dose chemotherapy in hematological malignancies [J].
Benner, E ;
Bishop, MR ;
Agarwal, N ;
Iversen, P ;
Joshi, SS .
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, 1997, 37 (04) :229-235