RT Journal Article
SR Electronic
T1 Tumor-specificity and Apoptosis-inducing Activity of Stilbenes and Flavonoids
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2055
OP 2063
VO 25
IS 3B
A1 CHOWDHURY, SHAHEAD ALI
A1 KISHINO, KAORI
A1 SATOH, RIE
A1 HASHIMOTO, KEN
A1 KIKUCHI, HIROTAKA
A1 NISHIKAWA, HIROFUMI
A1 SHIRATAKI, YOSHIAKI
A1 SAKAGAMI, HIROSHI
YR 2005
UL http://ar.iiarjournals.org/content/25/3B/2055.abstract
AB A total of eleven stilbenes [1-6] and flavonoids [7-11] were investigated for their tumor-specific cytotoxicity and apoptosis-inducing activity, using four human tumor cell lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG and promyelocytic leukemia HL-60) and three normal human oral cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF). All of the compounds, especially sophorastilbene A [1], (+)-α-viniferin [2], piceatannol [5], quercetin [9] and isoliquiritigenin [10], showed higher cytotoxicity against the tumor cell lines than normal cells, yielding tumor-specific indices of 3.6, 4.7, >3.5, >3.3 and 4.0, respectively. Among the seven cell lines, HSC-2 and HL-60 cells were the most sensitive to the cytotoxic action of these compounds. Sophorastilbene A [1], piceatannol [5], quercetin [9] and isoliquiritigenin [10] induced internucleosomal DNA fragmentation and activation of caspases -3, -8 and -9 dose-dependently in HL-60 cells. (+)-α-Viniferin [2] showed similar activity, but only at higher concentrations. All the compounds failed to induce DNA fragmentation and activated caspases to much lesser extents in HSC-2 cells. Western blot analysis showed that sophorastilbene A [1], piceatannol [5] and quercetin [9] did not induce any consistent changes in the expression of pro-apoptotic proteins (Bax, Bad) and anti-apoptotic protein (Bcl-2) in HL-60 and HSC-2 cells. An undetectable expression of Bcl-2 protein in control and drug-treated HSC-2 cells may explain the relatively higher sensitivity of this cell line to stilbenes and flavonoids. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved