Inhibition of Glycolysis and Respiration of Sarcoma-180 Cells by Echitamine Chloride

Abstract

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 effect of seasonal variation on the antineoplastic activity of Alstonia scholaris R. Br. in HeLa cells

“…The plants belonging to the family apocynaceae having anticancer properties like Adenium obesum, Ervatamia hycnea, Ochrasia elleptica, Rhazya stricta, Taberaemontana amygdalaefolia, Thevitia gaumer, and Vinca roseas have been reported to contain steroids and alkaloids (Sathyavathi et al, 1987;Graham et al, 2000). Cytotoxic studies with different fractions of ASE in the HeLa cells revealed best activity for ASERS followed by the ASE and ASECH, and the cytotoxic effect was better than that of ECL, a compound already reported to possess significant anticancer activity in vitro and in vivo (Saraswathi et al, 1997(Saraswathi et al, , 1998(Saraswathi et al, , 1999. This indicates that the observed anticancer activity of these fractions may be enhanced by the presence of certain other minor compounds in the extract and it may not solely be due to ECL.…”

“…was isolated from its alcoholic extract as described by Saraswathi et al (1997Saraswathi et al ( , 1998. The purity of the sample was confirmed by cochromatography, UV spectra and IR spectra and was compared with the authentic sample obtained from Dr. V. Mathurum, Captain Srinivasamurthy Drug Research institute for Ayurveda, Chennai, India.…”

Current Progress in the Chemistry and Pharmacology of Akuammiline Alkaloids

“…Likewise, a dosage of 5 mg/kg regulated the altered levels of drug-metabolizing enzymes and microsomal hemoproteins in diseased mice. In this work, echitamine chloride was shown to alter the synthesis of apoproteins by incorporation of labeled phenylalanine [107].…”

“…The in vitro viability of Ehrlich Ascites carcinoma cells was studied in the presence of a combination of echitamine chloride and vitamin A, since the latter has shown synergy in association with other anticancer drugs. The individual compounds displayed a weaker cytotoxic effect than a 200 to 10 µM combination of echitamine chloride and vitamin A as evidenced by corrected levels of lipid peroxides in plasma and studies on the incorporation of labeled thymidine in DNA [105]. The same researchers have investigated the cytotoxic effects of echitamine chloride in mice bearing S-180 solid tumor.…”

“…The daily administration of 5 mg/kg of the alkaloid reduced the pathological levels of serum glycoproteins and lysosomal hydrolases. In an effort to understand the mode of action of echitamine chloride, an extensive study on mitochondrial and cellular respiration of S-180 cells concluded that both processes are affected, shortening the energetic resources of the tumor cells [106]. Likewise, a dosage of 5 mg/kg regulated the altered levels of drug-metabolizing enzymes and microsomal hemoproteins in diseased mice.…”