Azadirachta indica exhibits chemopreventive action against hepatic cancer: Studies on associated histopathological and ultrastructural changes

Abstract

The present study was designed to evaluate the anticarcinogenic potential of Azadirachta indica against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. Further, the associated histopathological and ultrastructural changes were also analyzed. Hepatic cancer model was developed by the intraperitoneal administration of NDEA to mice at weekly intervals, in successive increasing doses, for a period of 8 weeks. Aqueous A. indica leaf extract (AAILE) was administered orally at a dosage of 100 μg/g body weight thrice a week till termination of the study. A relationship between histopathological grading and chemopreventive effect of A. indica had been established at various stages of carcinogenesis. Anticancer activity of A. indica was evaluated in terms of tumor incidence, tumor multiplicity, and survival rate. A significant reduction in tumor incidence (33%), tumor multiplicity (42%), and increase in survival (34%) was observed upon administration of AAILE to NDEA-abused mice. Transmission and scanning electron microscopic investigations showed severe alterations in organelle organization, cellular arrangement, degree of differentiation, cellular metabolism, and morphology of the hepatocytes. These changes appeared to be distinctly delayed upon AAILE supplementation. The results suggest A. indica may have anticancer potential against NDEA-induced hepatic cancer.

Spectroscopic Characterization of Lycopene Extract from Lycopersicum esculentum (Tomato) and Its Evaluation as a Chemopreventive Agent Against Experimental Hepatocarcinogenesis in Mice

“…The reduction in food intake and, consequently, the reduction in body weight observed in NDEA‐treated mice could be an indirect indication of the deteriorating hepatic function following exposure to carcinogen (NDEA). Several studies have shown similar reduction in the body weight of animals following the administration of NDEA (Hasegawa et al ., ; Sreepriya and Bali, ; Bharati et al ., ). The increase in hepatosomatic index in the NDEA‐treated group can be correlated to the morphological and histological observations such as increase in size of liver lobes hyperproliferation of cells, and tumour development (Cui et al ., ).…”

“…The control mice received olive oil (vehicle) at 0.1 mL orally thrice a week. The NDEA group received a cumulative dose of 200 mg/kg body weight of NDEA intraperitoneally in 8 weeks as described by Bharati et al ., . LycT was administered orally at a dosage of 5 mg/kg body weight in olive oil thrice a week throughout the experiment.…”

Azadirachta indica acts as a pro‐oxidant and modulates cell cycle associated proteins during DMBA/TPA induced skin carcinogenesis in mice

“…The anticancer action of Azadirachta indica ( A.indica ) against several animal cancer models and cell lines has been established . Studies have pointed out that A. indica affects biotransformation of carcinogens, generation of ROS/RNS, apoptosis, differentiation, proliferation and angiogenesis, which significantly influence the process of tumour formation .…”

“…The anticancer action of Azadirachta indica (A.indica) against several animal cancer models and cell lines has been established. [15][16][17][18][19] Studies have pointed out that A. indica affects biotransformation of carcinogens, generation of ROS/RNS, apoptosis, differentiation, proliferation and angiogenesis, which significantly influence the process of tumour formation. [20][21][22] Treatment of colon cancer cell line (HT-29) with a triterpenoid isolated from A. indica caused cell cycle arrest, indicating its ability to affect cell proliferation.…”

Lycopene treatment stalls the onset of experimentally induced hepatocellular carcinoma: a radioisotopic, physiological and biochemical analysis

“…The existing structural embodiment of our environment and surroundings makes impossible to evade the exposure from its pernicious clutches. Among various pollutants, N-nitrosodiethylamine (NDEA) is a potent environmental carcinogen found in air, soil, water and food [1][2][3] . Metabolic activation of NDEA through hepatic biotransformation enzymes renders liver as a target organ for carcinogenesis.…”