Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in-vitro and in tumour-bearing mice.
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.
Jagetia
Ganesh Chandra
GC
Department of Radiobiology, Kasturba Medical College, Manipal, India. gc.jagetia@rediffmail.com
Baliga
Manjeshwar Shrinath
MS
Venkatesh
Ponemone
P
Ulloor
Jagadish N
JN
Mantena
Sudheer Kumar
SK
Genebriera
Joseph
J
Mathuram
V
V
D000470:Alkaloids / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D031051:Alstonia / Q000737:chemistry; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D015227:Lipid Peroxidation / Q000187:drug effects; D008136:Longevity / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009026:Mortality; D009374:Neoplasms, Experimental; D024301:Plant Bark / Q000737:chemistry; D046948:Secologanin Tryptamine Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D015430:Weight Gain; D015431:Weight Loss
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D046948:Secologanin Tryptamine Alkaloids; D005978:Glutathione; C001133:echitamine