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Chemico-Biological Interactions Asiatic acid abridges pre-neoplastic lesions, inflammation, cell proliferation and induces apoptosis in a rat model of colon carcinogenesis
The colonic lumen is lined by a highly specialized epithelium composed primarily of goblet cells, which secrete mucin [63]. Mucin protects the epithelial lining against several injuries (inflammation, microbial invasion, toxins, pH, etc.) by forming a network via oligo-merization domains and thereby in the prevention of intestinal cancer[64]. Many studies suggest that analysis of the epithelial mucin activity is a valuable marker to predict and monitor the progression of colon cancer [65,66]. Our results portrayed goblet cells devoid of mucin ex-pression in DMH-alone-exposed rats, which could be due to the en-hanced release of mucinase enzyme leading to the hydrolysis of the protective mucins in the colon and exposure of the underlying epithelial cells to the carcinogens [67,68]. Treatment with AA significantly in-creased the mucin content in goblet cells as compared to DMH, which suggests that AA significantly protects the epithelial barriers against the carcinogen, DMH.
Previous studies reported that mast cells mediate tumour cellapoptosis through secretion of tumour necrosis factor (TNF-α) or by the production of reactive peroxides [69,70]. It indicates that these proin-flammatory mediators are involved in the pathogenesis of gastro-intestinal diseases. Mast cells are considered as innate immune cells which modulate colonic adenoma to carcinoma development. Our current study revealed increased numbers of mast cells in the colonic tissue of DMH-alone-administered rats, implicating the initiation of inflammatory cascade. However supplementation with AA to DMH-in-duced rats, reduced mast cell infiltration, and subsequently inflamma-tion and occurrence of adenocarcinoma induced by the carcinogen DMH.
Abnormal cellular proliferation is the prime contributor to carci-nogenesis [71].
...AA transduces apoptosis by the mi-tochondrial pathway...
In summary, the present study provides substantial evidence that AA inhibits DMH-induced colon carcinogenesis, which can be attributed to its ability in detoxifying the carcinogen, decreasing the preneoplastic lesions and exhibiting anti-inflammatory, anti-proliferative and proapoptotic eff ects. Further, our study also reveals that AA significantly attenuates the pathological alterations acquired by the colon and liver of the DMH-exposed rats. Among the three diff erent time periods of AA administration, the group in which AA was ad-ministered throughout the experimental period (EP) (group 6) showed the maximum inhibitory eff ect on DMH-induced colon carcinogenesis.Thus the outcome of this work infers that in presence of the chemical carcinogen DMH, AA can eff ectively induce apoptosis and protect against inflammation and proliferation. So AA, by virtue of its ability tomarkedly inhibit DMH-induced colon carcinogenesis could be a pro-mising candidate agent for cancer chemoprevention and anticancertherapeutics.
The colonic lumen is lined by a highly specialized epithelium composed primarily of goblet cells, which secrete mucin [63]. Mucin protects the epithelial lining against several injuries (inflammation, microbial invasion, toxins, pH, etc.) by forming a network via oligo-merization domains and thereby in the prevention of intestinal cancer[64]. Many studies suggest that analysis of the epithelial mucin activity is a valuable marker to predict and monitor the progression of colon cancer [65,66]. Our results portrayed goblet cells devoid of mucin ex-pression in DMH-alone-exposed rats, which could be due to the en-hanced release of mucinase enzyme leading to the hydrolysis of the protective mucins in the colon and exposure of the underlying epithelial cells to the carcinogens [67,68]. Treatment with AA significantly in-creased the mucin content in goblet cells as compared to DMH, which suggests that AA significantly protects the epithelial barriers against the carcinogen, DMH.
Previous studies reported that mast cells mediate tumour cellapoptosis through secretion of tumour necrosis factor (TNF-α) or by the production of reactive peroxides [69,70]. It indicates that these proin-flammatory mediators are involved in the pathogenesis of gastro-intestinal diseases. Mast cells are considered as innate immune cells which modulate colonic adenoma to carcinoma development. Our current study revealed increased numbers of mast cells in the colonic tissue of DMH-alone-administered rats, implicating the initiation of inflammatory cascade. However supplementation with AA to DMH-in-duced rats, reduced mast cell infiltration, and subsequently inflamma-tion and occurrence of adenocarcinoma induced by the carcinogen DMH.
Abnormal cellular proliferation is the prime contributor to carci-nogenesis [71].
...AA transduces apoptosis by the mi-tochondrial pathway...
In summary, the present study provides substantial evidence that AA inhibits DMH-induced colon carcinogenesis, which can be attributed to its ability in detoxifying the carcinogen, decreasing the preneoplastic lesions and exhibiting anti-inflammatory, anti-proliferative and proapoptotic eff ects. Further, our study also reveals that AA significantly attenuates the pathological alterations acquired by the colon and liver of the DMH-exposed rats. Among the three diff erent time periods of AA administration, the group in which AA was ad-ministered throughout the experimental period (EP) (group 6) showed the maximum inhibitory eff ect on DMH-induced colon carcinogenesis.Thus the outcome of this work infers that in presence of the chemical carcinogen DMH, AA can eff ectively induce apoptosis and protect against inflammation and proliferation. So AA, by virtue of its ability tomarkedly inhibit DMH-induced colon carcinogenesis could be a pro-mising candidate agent for cancer chemoprevention and anticancertherapeutics.