Abstract
The induction of phase II drug metabolizing enzymes serves as a detoxification mechanism for many mutagens, carcinogens and other toxic compounds. Specifically, NAD(P)H:quinone oxidoreductase 1 (Nqo1) and glutathione S-transferase Ya subunit (Gst ya) are key enzymes involved in cellular defense against reactive forms of oxygen and the inhibition of carcinogenesis. As(3+), which induces these enzymes, has been proven to have a role in the treatment of acute promyelocytic leukemia. Ascorbic acid (AA) potentiates the anticancer effect of As(3+) and thus it is expected that this antioxidant will have a paradoxical effect on the ability of heavy metals, specifically As(3+), to induce Nqo1 and Gst ya. We have shown that As(3+) and Cd(2+) induce heme oxygenase-1 (HO-1), Nqo1 and Gst ya mRNA levels but Cr(6+) decreases Nqo1 and Gst ya mRNA. Surprisingly, AA superinduced the induction of HO-1, Nqo1 and Gst ya mRNA by As(3+), while inhibiting the induction of HO-1 mRNA by Cd(2+) and Cr(6+). Hence, it is tempting to speculate that AA may potentiate the therapeutic efficacy of As(3+) by enhancing the expression of HO-1, Nqo1, and Gst ya while acting as a potent antioxidant.
References
May 1, 1989·In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association·T C LeeH Huang
Mar 1, 1989·Cancer·V NotoW De Loecker
Aug 1, 1995·Cancer Research·S AnttilaB Ketterer
Mar 1, 1995·Carcinogenesis·T KatohA Sugita
Aug 1, 1995·Pharmacogenetics·E A RosvoldK H Buetow
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·K D Poss, S Tonegawa
Sep 17, 1999·The Journal of Biological Chemistry·R YuA N Kong
Sep 29, 2000·Biochemical Pharmacology·S Immenschuh, G Ramadori
May 2, 2001·The Oncologist·A J Murgo
Jul 27, 2001·Blood·J M GradL H Boise
Dec 6, 2001·Protoplasma·G López-LluchP Navas
Jan 26, 2002·Molecular Pharmacology·Steven P RiveraOliver Hankinson
Feb 21, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·David C SpinkLaurence S Kaminsky
Oct 29, 2002·Leukemia & Lymphoma·T Bachleitner-HofmannH Gisslinger
Nov 26, 2003·Biochemical and Biophysical Research Communications·Jan C BeckerThorsten Pohle
Sep 1, 2004·Toxicology·Reem H Elbekai, Ayman O S El-Kadi
May 3, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Zheng Ye, Honglin Song
Jul 12, 2005·European Urology·Daya Shankar Lal SrivastavaRama Devi Mittal
Sep 21, 2005·The Prostate·Ilir AgalliuJanet L Stanford
Oct 6, 2005·Toxicology and Applied Pharmacology·Takashige KawakamiSeiichiroh Ohsako
Nov 9, 2005·Free Radical Biology & Medicine·Reem H Elbekai, Ayman O S El-Kadi
Citations
Jun 10, 2011·Archives of Pharmacal Research·Uraiwan PanichAdisak Wongkajornsilp
Jun 14, 2014·PloS One·Bing ZhaoEn-Qiang Mao
Aug 5, 2011·The American Journal of Clinical Nutrition·Gladys BlockNina Holland
Nov 13, 2014·BMC Complementary and Alternative Medicine·Bing ZhaoEn-Qiang Mao
Sep 17, 2010·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Weiti CuiWenbiao Shen
Feb 15, 2013·Toxicology and Industrial Health·P V KiruthigaK Pandima Devi
Aug 19, 2014·Journal of Biochemical and Molecular Toxicology·Anwesha ChatterjeeHari K Bhat
Jul 7, 2009·Toxicology and Applied Pharmacology·Ya-Ni HuangJia-Yi Wang