Myrtenal attenuates diethylnitrosamine-induced hepatocellular carcinoma in rats by stabilizing intrinsic antioxidants and modulating apoptotic and anti-apoptotic cascades.
BACKGROUND
Myrtenal, a natural monoterpene occurred in cumin, pepper, mint and eucalyptus. Monoterpenes are naturally occurring plant hydrocarbons composed of two isoprene units and are widely distributed in plant flora and are best known for occurrence in essential oils. Monoterpenes have been shown to have remarkable biological activities such as antioxidant, chemotherapeutic and chemopreventive effects in different models of cancer. The aim of the study was to investigate the antioxidant and anticancer activity of myrtenal against carcinogen induced hepatocellular caricinoma in rats.


METHODS
The antioxidant properties of myrtenal were evaluated by using different in vitro antioxidant assays such as by determining its scavenging effect against hydroxyl (OH(•)), superoxide anion (O2(•-)), nitric oxide, 1,1-diphenyl-2-picrylhydrazyl (DPPH(•)) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid radical cation (ABTS(•+)). In vivo antioxidant and anticancer activity of myrtenal were evaluated by determining the antioxidant enzymes, apoptotic and anti-apoptotic proteins such as Bcl-2, Bax and caspase-3 expression and histopathological analysis against the diethylnitrosamine induced hepatocellular carcinoma in wistar albino rats.


RESULTS
Our results demonstrated that myrtenal exhibits strong antioxidant property in all the in vitro assays and the in vivo results revealed that the antioxidant status was significantly decreased in hepatoma bearing animals. The expression of anti-apoptotic proteins was up regulated and in contrast the apoptotic protein was down regulated in hepatoma bearing animals. Treatment with myrtenal to cancer bearing animals resulted in remarkable increase in the inherent antioxidants and excellent modulation in the proteins of apoptotic and anti-apoptotic cascade. Further, the RT-PCR analysis of protein expressions and histological analysis of liver tissues inevitably confirms the anticancer property of myrtenal.


CONCLUSIONS
It is concluded that myrtenal exhibits excellent free radical scavenging activity and anticancer activity through the suppression of hepatocellular carcinoma in wistar rats. Thereby giving a positive insight to take this compound as an effective therapeutic agent against hepatoma.
Department of Pharmacology and Environmental Toxicology, Dr. A. L. M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu, India.
Lingaiah
L
Hari Babu
Srinivasan
S
Perumal
Maruthaiveeran Periyasamy
MP
Balasubramanian
D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D052160:Benzothiazoles / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D000081008:Bicyclic Monoterpenes; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015153:Blotting, Western; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004052:Diethylnitrosamine; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D010851:Picrates / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013451:Sulfonic Acids / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; D052160:Benzothiazoles; D000081008:Bicyclic Monoterpenes; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D010851:Picrates; D013451:Sulfonic Acids; D013729:Terpenes; D051028:bcl-2-Associated X Protein; D013481:Superoxides; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D004052:Diethylnitrosamine; C061545:myrtenal; C004931:1,1-diphenyl-2-picrylhydrazyl; D002374:Catalase; D013482:Superoxide Dismutase; D053148:Caspase 3