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ThesisItem Open Access EVALUATION OF ANTITUMOUR PROPERTIES OF SIMAROUBA GLAUCA (‘LAKSHMI TARU’) AND THESPESIA POPULNEA (‘POOVARASU’) IN EXPERIMENTAL MAMMARY TUMOUR MODELS IN RATS(COLLEGE OF VETERINARY AND ANIMAL SCIENCES MANNUTHY, THRISSUR, 2017-12-30) ANU G; Usha P. T. A.The present study was undertaken to evaluate the antitumour properties of Simarouba glauca (‘Lakshmi taru’) and Thespesia populnea (‘Poovarasu’) in in vitro cancer cell line and in DMBA (7, 12 dimethyl benz[a]anthracene) induced mammary tumours in rats. The crude alcoholic extracts and different fractions of S. glauca leaves and T. populnea bark were screened for their cytotoxic property in MCF-7 human breast carcinoma cell line. Based on the IC50 value, chloroform soluble fractions (CSF) of both S. glauca and T. populnea were found to be superior in cytotoxic action than crude extracts and other fractions, and hence CSFs of both the plants were selected for further in vitro and in vivo studies. In in vitro haemolytic assay, CSF of S. glauca did not produce haemolysis in any of the tested concentrations whereas CSF of T. populnea showed haemolytic activity in a dose dependent manner starting from the concentration 40 µg/mL. Chloroform soluble fractions of S. glauca and T. populnea exhibited a superior in vitro antioxidant effect in a dose dependent manner when compared with vitamin C standard. On phase contrast microscopy and Acridine orange/ ethidium bromide (AOEB) dual staining, MCF-7 cells treated with CSFs of S. glauca and T. populnea exhibited marked morphological and nuclear alterations which were characteristics of apoptosis. DNA ladder assay and TUNEL assay was conducted to detect the apoptotic DNA fragmentation if any, occurred in MCF-7 cells after treatment with the plant fractions. A typical ladder pattern characteristic of apoptosis was not observed in DNA ladder assay whereas, there was an increase in positive reactions noticed in TUNEL assay which indicates an increase in DNA fragmentation after the plant fraction treatments. In acute toxicity study (OECD Guidelines no. 423) in rats, there was no apparent toxic symptoms or mortality observed in both S. glauca and T. populnea treatment groups up to an oral dose of 2000 mg/kg body weight. For in vivo antitumour studies, DMBA induced rat mammary tumour model was used. Experimental study was conducted for 14 days with 12 animals in each group. 154 After treatment with S. glauca and T. populnea CSFs at the dose rates 50 mg/kg and 100 mg/kg, no significant changes were noticed on tumour volume, tumour weight and ratio of tumour weight to body weight. The elevated mean serum LDH levels decreased significantly in the treatment groups on days 7 and 14. When compared with normal control, SOD, CAT and GSH levels were noticed to increase whereas lipid peroxidation level reduced in the mammary tumour tissues after the plant fraction treatments. In AO/EB dual staining, an increased apoptotic and necrotic cell density was observed in both the plant fraction treatment groups in dose dependent manner. After treatment with CSFs of S. glauca and T. populnea, the antiapoptotic gene Bcl2 expression was downregulated both in in vitro and in vivo studies. On histopathological examination of the mammary tumour masses using H & E staining, a progressive reduction in cellularity and apoptotic changes were noticed in the plant fraction treated groups. Thus in the present study, CSF of ethanolic extract of S. glauca leaf and CSF of methanolic extract of T. populnea bark exhibited a dose dependent cytotoxic and antitumour activity both in vitro and in vivo. The plant fractions were effective in inducing apoptotic cell death and may be considered as potent sources for isolating therapeutic molecules for cancer treatment.
