Proliferation, angiogenesis and apoptosis-associated proteins are molecular targets for chemoprevention of MNNG-induced gastric carcinogenesis by ethanolic Ocimum sanctum leaf extract.
BACKGROUND
This study was designed to evaluate the chemopreventive effects of ethanolic Ocimum sanctum (OS) leaf extract on cell proliferation, apoptosis and angiogenesis during N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis.


METHODS
The rats were divided into four groups of ten each. Rats in group one were given MNNG (150 mg/kg body weight) by intragastric intubation three times, with a two-week interval between treatments. Rats in group two were administered MNNG as in group one, and in addition, they received intragastric intubation of ethanolic OS extract (300 mg/kg body weight) three times per week, starting on the day following the first exposure to MNNG. The intubation of ethanolic OS extract continued until the end of the experimental period. Rats in group three were given ethanolic OS leaf extract only. Group four served as controls. All the rats were killed after an experimental period of 26 weeks.


RESULTS
Intragastric administration of MNNG-induced well-differentiated squamous cell carcinomas that showed increased cell proliferation, and angiogenesis with evasion of apoptosis, as revealed by the upregulation of proliferating cell nuclear antigen (PCNA), glutathione S-transferase-pi (GST-pi), Bcl-2, cytokeratin (CK) and vascular endothelial growth factor (VEGF) and with downregulation of Bax, cytochrome C and caspase 3 protein expression. Administration of ethanolic OS leaf extract reduced the incidence of MNNG-induced gastric carcinomas. This was accompanied by decreased expression of PCNA, GST-pi, Bcl-2, CK and VEGF, and overexpression of Bax, cytochrome C, and caspase 3.


CONCLUSIONS
This study provides evidence that, in MNNG-induced gastric carcinogenesis, the key proteins involved in the proliferation, invasion, angiogenesis and apoptosis, are viable molecular targets for chemoprevention using ethanolic OS leaf extract.
Manikandan
P
P
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamil Nadu, India.
Vidjaya Letchoumy
P
P
Prathiba
D
D
Nagini
S
S
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D049109:Cell Proliferation / Q000187:drug effects; D018890:Chemoprevention; D004195:Disease Models, Animal; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000009:adverse effects; D009389:Neovascularization, Pathologic; D031339:Ocimum; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D018515:Plant Leaves; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects
D016588:Anticarcinogenic Agents; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D008769:Methylnitronitrosoguanidine