title: Cytotoxic effects of N'-formyl-2-(5-nitrothiophen-2-yl) benzothiazole-6-carbohydrazide in human breast tumor cells by induction of oxidative stress.
abstract: Chemically active molecules, such as reactive oxygen species (ROS), are prone to induce cellular damage by oxidative stress and this could be exploited as a strategy to kill malignant cells. In this study, we evaluated the antitumor activity of a new compound, N'-formyl-2-(5-nitrothiophen-2-yl)benzothiazole-6-carbohydrazide (FBZC) by assessing its pro-oxidant effects on breast cancer in vitro. Oxidative stress, generated by FBZC, was characterized by measuring reactive species and antioxidant enzymes and markers. Results showed that the cytotoxic effects of FBZC on MCF7 breast cancer cells (half inhibitory concentration of 5.4 μg/ml), were partially reversed by the addition of regular antioxidants. FBZC induced ROS and lipid peroxidation, together with a significant inhibition of superoxide dismutase, glutathione reductase and total glutathione levels as well as increases in catalase and glutathione-S-transferase activities, in an acute fast response. Thus, the antitumor effects of FBZC could be related to oxidative deregulation due to a combination of induction of ROS generation and inhibition of key antioxidant enzymes.
authors: Laboratory of Biochemistry of Oxidants and Antioxidants, Centre and Department of Chemistry and Biochemistry, School of Sciences, University of Lisbon, Lisbon, Portugal. juanricardorodrigues@gmail.com
authors: Juan R
authors: JR
authors: Rodrigues
authors: Jaime
authors: J
authors: Charris
authors: José
authors: J
authors: Camacho
authors: Arthur
authors: A
authors: Barazarte
authors: Neira
authors: N
authors: Gamboa
authors: Fernando
authors: F
authors: Antunes
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D052160:Benzothiazoles / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D052160:Benzothiazoles; D006834:Hydrazines; C575386:N'-formyl-2-(5-nitrothiophen-2-yl)benzothiazole-6-carbohydrazide; D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione