Chemopreventive and therapeutic modulation of green tea polyphenols on drug metabolizing enzymes in 4-Nitroquinoline 1-oxide induced oral cancer.
Oral cancer is one of the most common cancers in the world. Drugs can modulate the expression of drug metabolizing enzymes and are useful in chemoprevention as well as therapy in cancer. 4-Nitroquinoline 1-oxide (4-NQO) is used to induce oral cancer in the present study. In the present investigation, the effect of green tea polyphenols (GTP) on the activities of cytochrome b5, cytochrome P450, cytochrome b5 reductase (cyt b5 R), cytochrome P450 reductase (cyt P450 R), arryl hydrocarbon hydroxylase (AHH), DT-diaphorase (DTD)(Phase I enzymes) and glutathione-S-transferase (GST) and UDP-glucuronyl transferase (UDP-GT) (Phase II enzymes) were assessed in tongue and oral cavity. In induced rats, there was a decrease in the activity of Phase II enzymes and an increase in the activity of Phase I enzymes. On supplementation of GTP by both simultaneous and post treatment mode (200mg/kg) there was a significant increase in the activity of GST and UDP-GT and a significant decrease in the activity of Phase I enzymes. There was a significant decline in the number of tumors, tumor volume and oral squamous cell carcinoma in both simultaneous and post GTP treated animals relative to 4-NQO induced animals; on comparing simultaneous and post GTP treated animals the number of tumors, tumor volume and oral squamous cell carcinoma was significantly reduced in post treated animals. Thus inhibition of Phase I enzymes could be attributed to the protective efficacy of GTP which deactivates carcinogen and GTP induced the expression of Phase II enzymes that detoxifies the 4-NQO. It can be proposed that GTP plays role as a detoxifying agent by which its modulating role prevented/inhibited the formation of tumor.
Srinivasan
Periasamy
P
Team for Radiation Food Science and Biotechnology, Radiation Application Research Division, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeonbuk 580-185, Republic of Korea. sreezen@rediffmail.com
Suchalatha
Subramaniyan
S
Babu
Pon Velayutham Anandh
PV
Devi
Rethinam Sundaresan
RS
Narayan
Shoba
S
Sabitha
Kuruvimalai Ekambaram
KE
Shyamala Devi
Chennam Srinivasulu
CS
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D042966:Cytochrome-B(5) Reductase / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008297:Male; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D059808:Polyphenols; D051381:Rats; D017208:Rats, Wistar; D013662:Tea / Q000737:chemistry*
D000970:Antineoplastic Agents; D000975:Antioxidants; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D013662:Tea; D015112:4-Nitroquinoline-1-oxide; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D042966:Cytochrome-B(5) Reductase; D016660:NAD(P)H Dehydrogenase (Quinone); D014453:Glucuronosyltransferase; D005982:Glutathione Transferase