Fisetin modulates mitochondrial enzymes and apoptotic signals in benzo(a)pyrene-induced lung cancer.
The present study was aimed to delineate in vivo mechanisms of orally administered fisetin with special reference to mitochondrial dysfunction in lung tissues employing benzo(a)pyrene (B(a)P) as the model lung carcinogen. The recent revival of interest in the study of mitochondria has been stimulated by the evidence that genetic and/or metabolic alterations in this organelle lead to a variety of human diseases including cancer. These alterations could be either causative or contributing factors. Hence, the activities of mitochondrial-specific enzymes of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and tumor marker, carcinogenic embryonic antigen were analyzed in control and experimental groups of mice. The induction of apoptotic and anti-apoptotic proteins such as Bcl-2/Bax, cytochrome c, caspase-9 and caspase-3 was confirmed by the immunohistochemistry and Western blot analyses. Furthermore, transmission electron microscopy study of lung sections of B(a)P-induced mice showed the presence of phaemorphic cells with dense granules and increased mitochondria. All the aberrations were alleviated when the mice were treated with fisetin (25 mg/kg body weight). The results proved fisetin to be a very successful drug in combating the mitochondrial dysfunction in an experimental model of lung carcinogenesis induced by B(a)P.
Department of Biotechnology, School of Life Science, Guindy Campus, University of Madras, Chennai, 600025, Tamil Nadu, India.
Nagaiya
N
Ravichandran
Gopal
G
Suresh
Balasubramanian
B
Ramesh
Ramar
R
Manikandan
Young Whan
YW
Choi
Ganesan
G
Vijaiyan Siva
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001564:Benzo(a)pyrene / Q000633:toxicity; D005419:Flavonoids / Q000008:administration & dosage*; D044948:Flavonols; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015227:Lipid Peroxidation / Q000235:genetics; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D018384:Oxidative Stress / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
D016588:Anticarcinogenic Agents; D051017:Apoptosis Regulatory Proteins; D005419:Flavonoids; D044948:Flavonols; D001564:Benzo(a)pyrene; C017875:fisetin