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Molecular and Cellular Biochemistry

, Volume 369, Issue 1–2, pp 183–193 | Cite as

Myrtenal, a natural monoterpene, down-regulates TNF-α expression and suppresses carcinogen-induced hepatocellular carcinoma in rats

  • Lingaiah Hari Babu
  • Srinivasan Perumal
  • Maruthaiveeran Periyasamy Balasubramanian
Article

Abstract

Hepatocellular carcinoma is one of the most common cancers and lethal diseases in the world. Recently, many researchers focused to identify novel chemotherapeutic agents from natural sources against hepatocarcinogenesis. The diverse therapeutic potential of essential oils has drawn the attention of researchers to test them for anticancer activity, taking advantage of the fact that their mechanism of action is dissimilar to that of chemotherapeutic agents. Earlier reports indicated that essential oil components, especially monoterpenes, have multiple pharmacological effects which could account for the terpene-tumor suppressive activity. In the present study, it is shown that myrtenal, a natural monoterpene, which acts as an antineoplastic agent against diethylnitrosamine induced phenobarbital promoted experimental hepatocellular carcinoma. The results revealed an elevated level of microsomal lipid peroxidation in the liver, which was found to be significantly reduced by myrtenal treatment. On the contrary, the Phase I hepatic drug metabolizing enzymes’ (cytochrome P450, cytochrome b 5, NADPH-cytochrome c reductase, NADH-cytochrome b 5 reductase) levels were decreased and the Phase II enzymes (glutathione-S-transferase, uridine 5′-diphospho-glucuronyl transferase) were increased in carcinogen-administered animals, which were reverted to near normalcy upon myrtenal administration. Our findings also showed that myrtenal restrains the liver cancer by preventing the DEN–PB induced up-regulation of TNF-α protein expression by immunoblot. Furthermore, transmission electron microscopic examination also indicated that myrtenal prevents the carcinogen-induced changes in the architecture of liver tissue and cell structure. Thus, this study shows that myrtenal has the ability to suppress the hepatocellular carcinoma in rats.

Keywords

Monoterpene Myrtenal Diethylnitrosamine Hepatocellular carcinoma TNF-α 

Abbreviations

HCC

Hepatocellular carcinoma

DEN

Diethylnitrosamine

PB

Phenobarbital

AFP

α-Fetoprotein

CEA

Carcinoembryonic antigen

LPO

Lipid peroxidation

MDA

Malondialdehyde

GST

Glutathione-S-transferase

UDP-GT

Uridine 5′-diphospho-glucuronyl transferase

TNF-α

Tumor necrosis factor-α

FADD

Fas-associated death domain

TADD

TNF receptor 1 associated death domain

Notes

Acknowledgments

The authors are extremely grateful to Dr. R.Venkatakrishna Murali, M.D., Ph.D., Professor and Head, Department of Pharmacology and Environmental Toxicology, Dr. ALMPGIBMS, the University of Madras, Taramani, Chennai, India, for providing the laboratory facilities, and Dr. Stephen Poole, Parenterals Section Leader, the National Institute for Biological Standards and Control, South Mimms, UK, who gifted the TNF-α antibody for the study.

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Lingaiah Hari Babu
    • 1
  • Srinivasan Perumal
    • 1
  • Maruthaiveeran Periyasamy Balasubramanian
    • 1
  1. 1.Department of Pharmacology and Environmental Toxicology, Dr. A. L. Mudhaliar Post Graduate Institute of Basic Medical SciencesUniversity of MadrasChennaiIndia

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