title: Myrtenal ameliorates diethylnitrosamine-induced hepatocarcinogenesis through the activation of tumor suppressor protein p53 and regulation of lysosomal and mitochondrial enzymes.
abstract: Myrtenal is a novel class of compound belongs to monoterpenes found predominantly in mint, pepper, etc., and it was shown to have excellent pharmacological activities against many diseases among which cancer is imperative. Hepatocellular carcinoma is a primary malignancy of the hepatocytes, which rapidly leads to death in short periods. The aim of this study was to investigate the possible therapeutic efficiency of myrtenal against diethylnitrosamine-induced experimental hepatocarcinogenesis by analyzing the key enzymes of carbohydrate metabolism, lysosomal and mitochondrial TCA cycle enzymes, and also the possible role of tumor suppressor protein p53, and scanning electron microscopic studies. The results revealed that myrtenal significantly ameliorated the altered enzymes of carbohydrate metabolism, lysosomal and mitochondrial enzymes, and interestingly the tumor suppressor protein p53 was found to be significantly accumulated in myrtenal-treated animals, which inevitably confirms that myrtenal has a prominent role in preventing the liver cancer during treatment. Furthermore, the antineoplastic property was well evidenced by the mRNA expression of p53 protein by the reverse-transcriptase polymerase chain reaction and immunoblot analysis. The observed anticancer property of myrtenal may be due to the involvement and expression of p53 and influence in the mitochondrial and lysosomal membrane integrity and also interference in the gluconeogenesis process of cancer cells. Our results suggest that myrtenal is very efficient and useful compound in the treatment of liver cancer in future.
authors.affiliation: Dr. ALM Post Graduate Institute of Basic Medical Sciences, Department of Pharmacology and Environmental Toxicology, University of Madras, Tharamani Campus, Chennai - 600113, Tamil Nadu, India.
authors.forename: Hari Babu
authors.initials: HB
authors.lastname: Lingaiah
authors.forename: Nandakumar
authors.initials: N
authors.lastname: Natarajan
authors.forename: Rengarajan
authors.initials: R
authors.lastname: Thamaraiselvan
authors.forename: Perumal
authors.initials: P
authors.lastname: Srinivasan
authors.forename: Balasubramanian Maruthaiveeran
authors.initials: BM
authors.lastname: Periyasamy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000081008:Bicyclic Monoterpenes; D050260:Carbohydrate Metabolism / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002952:Citric Acid Cycle / Q000187:drug effects; D004052:Diethylnitrosamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005943:Gluconeogenesis / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D017208:Rats, Wistar; D013729:Terpenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D000081008:Bicyclic Monoterpenes; D012333:RNA, Messenger; D013729:Terpenes; D016159:Tumor Suppressor Protein p53; D004052:Diethylnitrosamine; C061545:myrtenal