Malignant tumors are known to exhibit high rates of glycolytic activity leading to high production of lactic acid. Hence, neoplastic cells have elevated activity of enzymes responsible for glycolysis. Echitamine chloride, an indole alkaloid extracted from the bark of Alstonia scholaris, has been reported to have a highly promising anticancer activity against fibrosarcoma in rats. In the present study, the effect of echitamine chloride on energy metabolism of S-180 cells is investigated to have a better understanding on the mode of action of echitamine chloride. The effect of echitamine chloride on the mitochondrial and cellular respiration of S-180 cells was studied. Also, the effects on glucose utilization, pyruvate utilization and lactate formation were studied on whole S-180 cells and S-180 cell-free homogenate. The levels of glycolytic enzymes such as hexokinase and lactate dehydrogenase were estimated in which particular emphasis has been laid on hexokinase which occurs both in cytosolic and particulate forms in neoplastic cells. Hence the differential effect of echitamine chloride on the levels of total, cytosolic and particulate hexokinase has been investigated. In conclusion, echitamine chloride affects both cellular and mitochondrial respiration, leading to reduction of the cellular energy pool and thereby resulting in the loss of viability of S-180 cells.
The cytotoxic effect of various concentrations of echitamine chloride was studied in HeLa, HepG2, HL60, KB and MCF-7 cell lines in-vitro and in mice bearing Ehrlich ascites carcinoma (EAC). Exposure of various cells to different concentrations of echitamine chloride resulted in a concentration-dependent cell killing, and KB cells were found to be most sensitive amongst all the cells evaluated. EAC mice treated with 1, 2, 4, 6, 8, 12 or 16 mg kg-1 echitamine chloride showed a dose-dependent elevation in the anti-tumour activity, as evident by increased number of survivors in comparison with the non-drug treated controls. The highest dose of echitamine chloride (16 mg kg-1) caused toxicity in the recipient mice, therefore 12 mg kg-1 was considered the best cytotoxic dose for its anti-tumour effect. Administration of 12 mg kg-1 echitamine chloride resulted in an increase in the median survival time (MST) up to 30.5 days, which was 11.5 days higher than the non-drug treated control (19 days). Administration of 16 mg kg-1 echitamine chloride to EAC mice resulted in a time dependent elevation in lipid peroxidation that reached a peak at 6 h post-treatment, whereas glutathione concentration declined in a time dependent manner and a maximum decline was reported at 3 h post-treatment. Our study demonstrated that echitamine chloride possessed anti-tumour activity in-vitro and in-vivo.
The chloroform extract of dried leaves of Trichilia connaroides, was screened for analgesic and antiinflammatory activity, using chemical-, thermal-and formalin-induced inflammation in Swiss mice and Wistar rats. Chloroform extract showed significant and dose-dependent analgesic, and antiinflammatory activity.
The structures of arbortristosides A and B have been reinvestigated by proton decoupling experiments and 2D correlated nmr spectroscopy. The aryl ester groups in both arbortristosides A and B have been found to be at position 7, not at 6 as reported earlier.
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