TY - JOUR
T1 - N-Acetylcysteine enhances the lung cancer inhibitory effect of epigallocatechin-3-gallate and forms a new adduct
AU - Lambert, Joshua D.
AU - Sang, Shengmin
AU - Yang, Chung S.
N1 - Funding Information:
This work was supported by American Institute for Cancer Research Grant 05A047 (to J.D.L.), National Cancer Institute Grant CA125780 (to J.D.L.), and National Cancer Institute Grant CA121390 (to S.S.). The authors acknowledge technical assistance from Dr. Hang Xiao and Ms. Joan DuBois.
PY - 2008/3/15
Y1 - 2008/3/15
N2 - The major tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), inhibits carcinogenesis in many in vivo models. Many potential mechanisms of action have been proposed based on cell line studies, including prooxidant activity. In the present study, we studied the effect of N-acetylcysteine (NAC) on the inhibitory effects of EGCG on lung cancer cell growth. We found that NAC (0-2 mM) dose dependently enhanced the growth inhibitory activity of EGCG against murine and human lung cancer cells. The combination of NAC and EGCG caused an 8.8-fold increase in apoptosis in CL13 mouse lung cancer cells compared to treatment with either agent alone. Addition of 2 mM NAC increased the stability of EGCG in the presence of CL13 cells (t1/2 = 8.5 h vs 22.7 h). Intracellular levels of EGCG were increased 5.5-fold by the addition of 2 mM NAC. HPLC and LC-MS analyses of cell culture medium from CL13 cells treated with EGCG and NAC for 24 h revealed that EGCG-2′-NAC was time dependently formed. This adduct was not formed in the absence of NAC. The present results show that under cell culture conditions, EGCG and NAC interact to form a previously unreported adduct, EGCG-2′-NAC, which may contribute to enhancement of EGCG-mediated cell killing.
AB - The major tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), inhibits carcinogenesis in many in vivo models. Many potential mechanisms of action have been proposed based on cell line studies, including prooxidant activity. In the present study, we studied the effect of N-acetylcysteine (NAC) on the inhibitory effects of EGCG on lung cancer cell growth. We found that NAC (0-2 mM) dose dependently enhanced the growth inhibitory activity of EGCG against murine and human lung cancer cells. The combination of NAC and EGCG caused an 8.8-fold increase in apoptosis in CL13 mouse lung cancer cells compared to treatment with either agent alone. Addition of 2 mM NAC increased the stability of EGCG in the presence of CL13 cells (t1/2 = 8.5 h vs 22.7 h). Intracellular levels of EGCG were increased 5.5-fold by the addition of 2 mM NAC. HPLC and LC-MS analyses of cell culture medium from CL13 cells treated with EGCG and NAC for 24 h revealed that EGCG-2′-NAC was time dependently formed. This adduct was not formed in the absence of NAC. The present results show that under cell culture conditions, EGCG and NAC interact to form a previously unreported adduct, EGCG-2′-NAC, which may contribute to enhancement of EGCG-mediated cell killing.
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U2 - 10.1016/j.freeradbiomed.2007.12.016
DO - 10.1016/j.freeradbiomed.2007.12.016
M3 - Article
C2 - 18206665
AN - SCOPUS:39949085226
SN - 0891-5849
VL - 44
SP - 1069
EP - 1074
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 6
ER -
