Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in-vitro and in tumour-bearing mice

G.C. Jagetia, M.S. Baliga, P. Venkatesh, J.N. Ulloor, S.K. Mantena, J. Genebriera, V. Mathuram

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Abstract

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 (EAQ. 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 mgkg-1) caused toxicity in the recipient mice, therefore 12 mgkg-1 was considered the best cytotoxic dose for its anti-tumour effect. Administration of 12 mgkg-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 mgkg-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. © 2005 The Authors.
Original languageEnglish
Pages (from-to)1213-1219
Number of pages7
JournalJournal of Pharmacy and Pharmacology
Volume57
Issue number9
DOIs
Publication statusPublished - 2005
Externally publishedYes

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Indole Alkaloids
Monoterpenes
Chlorides
Neoplasms
KB Cells
MCF-7 Cells
In Vitro Techniques
echitamine
Ascites
Lipid Peroxidation
Glutathione
Carcinoma
Cell Line

Cite this

Jagetia, G. C., Baliga, M. S., Venkatesh, P., Ulloor, J. N., Mantena, S. K., Genebriera, J., & Mathuram, V. (2005). Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in-vitro and in tumour-bearing mice. Journal of Pharmacy and Pharmacology, 57(9), 1213-1219. https://doi.org/10.1211/jpp.57.9.0017
Jagetia, G.C. ; Baliga, M.S. ; Venkatesh, P. ; Ulloor, J.N. ; Mantena, S.K. ; Genebriera, J. ; Mathuram, V. / Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in-vitro and in tumour-bearing mice. In: Journal of Pharmacy and Pharmacology. 2005 ; Vol. 57, No. 9. pp. 1213-1219.
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title = "Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in-vitro and in tumour-bearing mice",
abstract = "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 (EAQ. 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 mgkg-1) caused toxicity in the recipient mice, therefore 12 mgkg-1 was considered the best cytotoxic dose for its anti-tumour effect. Administration of 12 mgkg-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 mgkg-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. {\circledC} 2005 The Authors.",
author = "G.C. Jagetia and M.S. Baliga and P. Venkatesh and J.N. Ulloor and S.K. Mantena and J. Genebriera and V. Mathuram",
note = "Cited By :18 Export Date: 10 November 2017 CODEN: JPPMA Correspondence Address: Jagetia, G.C.; Department of Radiobiology, Kasturba Medical College, Manipal-576 104, Karnataka, India; email: gc.jagetia@rediffmail.com Chemicals/CAS: doxorubicin, 23214-92-8, 25316-40-9; glutathione, 70-18-8; Alkaloids; Antineoplastic Agents, Phytogenic; echitamine, 6871-44-9; Glutathione, 70-18-8; Secologanin Tryptamine Alkaloids References: Abramowitz, M., Stegun, I.A., (1972) Handbook of Mathematical Functions, p. 925. , Dover Publications, Inc. New York, Library of Congress Catalog card number 65-12253; Adwankar, M.K., Chitnis, M.P., In vivo anti-cancer activity of RC-18: A plant isolate from Rubia cordifolia, Linn. Against a spectrum of experimental tumour models (1982) Chemotherapy, 28, pp. 291-293; Beljanski, M., Beljanski, M.S., Three alkaloids as selective destroyers of cancer cells in mice. Synergy with classic anticancer drugs (1986) Oncology, 43, pp. 198-203; Boritzki, T.J., Wolfard, T.S., Besserer, J.A., Jackson, R.C., Fry, D.W., Inhibition of type II topoisomerase by fostriecin (1988) Biochem. Pharmacol., 37, pp. 4063-4068; Bruller, W., Studies concerning the effect of Ukrain in vivo and in vitro (1992) Drugs Exp. Clin. Res., 18, pp. 13-16; Buege, J.A., Aust, S.D., Microsomal lipid peroxidation (1978) Methods Enzymol., 52, pp. 302-310; (1992) Selected Medicinal Plants of India, pp. 205-207. , Basic Chemicals, Pharmaceutical and Cosmetic Export Promotion Council, Bombay 400 039, India; Cragg, G.M., Newman, D.J., Weiss, R.B., Coral reefs, forests, and thermal vents: The worldwide exploration of nature for novel antitumor agents (1997) Semin. Oncol., 24, pp. 156-163; Geran, R.I., Greenberg, N.H., MacDonald, M.M., Schumacher, A.M., Abbott, B.J., Protocols for screening chemical agents and natural products against animal tumors and other biological systems (1972) Cancer Chemother. Rep., 2, pp. 1-85; Jagetia, G.C., Baliga, M.S., Modulation of antineoplastic activity of cyclophosphamide by Alstonia scholaris in the Ehrlich ascites carcinoma-bearing mice (2003) J. Exp. Ther. Oncol., 3, pp. 272-282; Jagetia, G.C., Baliga, M.S., Effect of Alstonia scholaris in enhancing the anticancer activity of berberine in the Ehrlich ascites carcinoma-bearing mice (2004) J. Med. Food, 7, pp. 235-244; Jagetia, G.C., Baliga, M.S., The effect of seasonal variation on the antineoplastic activity of Alstonia scholaris R. Br. in HeLa cells (2005) J. Ethnopharmacol., 96, pp. 37-42; Kamarajan, P., Sekar, N., Mathuram, V., Govindasamy, S., Antitumor effect of echitamine chloride on methylcholonthrene induced fibrosarcoma in rats (1991) Biochem Int., 25, pp. 491-498; Kamarajan, P., Ramamurthy, N., Govindasamy, S., In vitro evaluation of the anticancer effects of echitamine chloride on fibrosarcoma cells (1995) J. Clin. Biochem. Nutr., 18, pp. 65-71; Keawpradub, N., Houghton, P.J., Eno-Amooquaye, E., Burke, P.J., Activity of extracts and alkaloids of Thai Alstonia species against human lung cancer cell lines (1997) Planta Med., 63, pp. 97-101; Keawpradub, N., Eno-Amooquaye, E., Burke, P.J., Houghton, P.J., Cytotoxic activity of indole alkaloids from Alstonia macrophylla (1999) Planta Med., 65, pp. 311-315; Krishnaswamy, M., Purushothaman, K.K., Plumbagin: A study of its anticancer, antibacterial & antifungal properties (1980) Indian J. Exp. Biol., 18, pp. 876-877; Mann, J., Natural products in cancer chemotherapy: Past, present and future (2002) Nature Rev. Cancer, 2, pp. 143-148; Mohana, K., Purushothaman, K.K., Susan, T., Drug potential of echitamine chloride in cancer chemotherapy (1985) Bulletin Medico-Ethno-Botanical Res., 6, pp. 124-132; Moron, M.S., Depierre, J.W., Mannervik, B., Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver (1979) Biochim. Biophys. Acta, 582, pp. 67-78; Nadkarni, A.K., (1976) Indian Materia Medica. 3rd Edn., , Popular Press Ltd, Mumbai, India; Nias, A.H.W., Radiation biology (1990) Treatment of Cancer, pp. 53-75. , Sikora, K., Halnan, K. E. (eds). Chapman and Hall Medical, London; Pezzuto, J.M., Plant-derived anticancer agents (1997) Biochem. Pharmacol., 53, pp. 121-133; Pratt, R.M., Willis, W.D., In vitro screening assay for teratogens using growth inhibition of human embryonic cells (1985) Proc. Natl. Acad. Sci. USA, 82, pp. 5791-5794; Quetin-Leclercq, J., Bouzahzah, B., Pons, A., Greimers, R., Angenot, L., Bassleer, R., Barbason, H., Strychnopentamine, a potential anticancer agent (1993) Planta Med., 59, pp. 59-62; Rajic, A., Kweifio-Okai, G., Macrides, T., Sandeman, R.M., Chandler, D.S., Polya, G.M., Inhibition of serine proteases by anti-inflammatory triterpenoids (2000) Planta Med., 66, pp. 206-210; Ramirez, A., Garcia-Rubio, S., Current progress in the chemistry and pharmacology of akuammiline alkaloids (2003) Curr. Med. Chem., 10, pp. 1891-1915; Saraswathi, V., Ramamurthy, N., Subramanian, S., Mathuram, V., Govindasamy, S., Enhancement of the cytotoxic effects of echitamine chloride by vitamin A: An in vitro study on Ehrlich ascites carcinoma cell culture (1997) Ind. J. Pharmacol., 29, pp. 244-249; Saraswathi, V., Ramamoorthy, N., Subramaniam, S., Mathuram, V., Gunasekaran, P., Govindasamy, S., Inhibition of glycolysis and respiration of sarcoma-180 cells by echitamine chloride (1998) Chemotherapy, 44, pp. 198-205; Saraswathi, V., Shyamala, A.C., Subramanian, S., Govindasamy, S., Mathuram, V., Studies on the effect of echitamine chloride on serum glycoproteins and lysosomal hydrolases of sarcoma-180 induced mice (1998) Fitoterapia, 1, pp. 73-76; Satyavati, G.V., Gupta, A.K., Tandon, N., (1987) Medicinal Plants of India, 2, pp. 230-239. , Indian Council of Medical Research, New Delhi, India; Sharada, A.C., Solomon, F.E., Devi, P.U., Udupa, N., Srinivasan, K.K., Antitumor and radiosensitizing effects of withaferin a on mouse Ehrlich ascites carcinoma in vivo (1996) Acta Oncol., 35, pp. 95-100; Uma Devi, P., Solomon, F.E., Sharada, A.C., Plumbagin, a plant naphthoquinone with antitumor and radiomodifying properties (1999) Pharmaceut. Biol., 37, pp. 231-236; Warrier, P.K., Nambiar, V.P.K., Ramankutty, C., (1996) Indian Medicinal Plants, pp. 1-5. , Orient Longman Limited, Hyderbad, India",
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Jagetia, GC, Baliga, MS, Venkatesh, P, Ulloor, JN, Mantena, SK, Genebriera, J & Mathuram, V 2005, 'Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in-vitro and in tumour-bearing mice', Journal of Pharmacy and Pharmacology, vol. 57, no. 9, pp. 1213-1219. https://doi.org/10.1211/jpp.57.9.0017

Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in-vitro and in tumour-bearing mice. / Jagetia, G.C.; Baliga, M.S.; Venkatesh, P.; Ulloor, J.N.; Mantena, S.K.; Genebriera, J.; Mathuram, V.

In: Journal of Pharmacy and Pharmacology, Vol. 57, No. 9, 2005, p. 1213-1219.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in-vitro and in tumour-bearing mice

AU - Jagetia, G.C.

AU - Baliga, M.S.

AU - Venkatesh, P.

AU - Ulloor, J.N.

AU - Mantena, S.K.

AU - Genebriera, J.

AU - Mathuram, V.

N1 - Cited By :18 Export Date: 10 November 2017 CODEN: JPPMA Correspondence Address: Jagetia, G.C.; Department of Radiobiology, Kasturba Medical College, Manipal-576 104, Karnataka, India; email: gc.jagetia@rediffmail.com Chemicals/CAS: doxorubicin, 23214-92-8, 25316-40-9; glutathione, 70-18-8; Alkaloids; Antineoplastic Agents, Phytogenic; echitamine, 6871-44-9; Glutathione, 70-18-8; Secologanin Tryptamine Alkaloids References: Abramowitz, M., Stegun, I.A., (1972) Handbook of Mathematical Functions, p. 925. , Dover Publications, Inc. New York, Library of Congress Catalog card number 65-12253; Adwankar, M.K., Chitnis, M.P., In vivo anti-cancer activity of RC-18: A plant isolate from Rubia cordifolia, Linn. Against a spectrum of experimental tumour models (1982) Chemotherapy, 28, pp. 291-293; Beljanski, M., Beljanski, M.S., Three alkaloids as selective destroyers of cancer cells in mice. Synergy with classic anticancer drugs (1986) Oncology, 43, pp. 198-203; Boritzki, T.J., Wolfard, T.S., Besserer, J.A., Jackson, R.C., Fry, D.W., Inhibition of type II topoisomerase by fostriecin (1988) Biochem. Pharmacol., 37, pp. 4063-4068; Bruller, W., Studies concerning the effect of Ukrain in vivo and in vitro (1992) Drugs Exp. Clin. Res., 18, pp. 13-16; Buege, J.A., Aust, S.D., Microsomal lipid peroxidation (1978) Methods Enzymol., 52, pp. 302-310; (1992) Selected Medicinal Plants of India, pp. 205-207. , Basic Chemicals, Pharmaceutical and Cosmetic Export Promotion Council, Bombay 400 039, India; Cragg, G.M., Newman, D.J., Weiss, R.B., Coral reefs, forests, and thermal vents: The worldwide exploration of nature for novel antitumor agents (1997) Semin. Oncol., 24, pp. 156-163; Geran, R.I., Greenberg, N.H., MacDonald, M.M., Schumacher, A.M., Abbott, B.J., Protocols for screening chemical agents and natural products against animal tumors and other biological systems (1972) Cancer Chemother. Rep., 2, pp. 1-85; Jagetia, G.C., Baliga, M.S., Modulation of antineoplastic activity of cyclophosphamide by Alstonia scholaris in the Ehrlich ascites carcinoma-bearing mice (2003) J. Exp. Ther. Oncol., 3, pp. 272-282; Jagetia, G.C., Baliga, M.S., Effect of Alstonia scholaris in enhancing the anticancer activity of berberine in the Ehrlich ascites carcinoma-bearing mice (2004) J. Med. Food, 7, pp. 235-244; Jagetia, G.C., Baliga, M.S., The effect of seasonal variation on the antineoplastic activity of Alstonia scholaris R. Br. in HeLa cells (2005) J. Ethnopharmacol., 96, pp. 37-42; Kamarajan, P., Sekar, N., Mathuram, V., Govindasamy, S., Antitumor effect of echitamine chloride on methylcholonthrene induced fibrosarcoma in rats (1991) Biochem Int., 25, pp. 491-498; Kamarajan, P., Ramamurthy, N., Govindasamy, S., In vitro evaluation of the anticancer effects of echitamine chloride on fibrosarcoma cells (1995) J. Clin. Biochem. Nutr., 18, pp. 65-71; Keawpradub, N., Houghton, P.J., Eno-Amooquaye, E., Burke, P.J., Activity of extracts and alkaloids of Thai Alstonia species against human lung cancer cell lines (1997) Planta Med., 63, pp. 97-101; Keawpradub, N., Eno-Amooquaye, E., Burke, P.J., Houghton, P.J., Cytotoxic activity of indole alkaloids from Alstonia macrophylla (1999) Planta Med., 65, pp. 311-315; Krishnaswamy, M., Purushothaman, K.K., Plumbagin: A study of its anticancer, antibacterial & antifungal properties (1980) Indian J. Exp. Biol., 18, pp. 876-877; Mann, J., Natural products in cancer chemotherapy: Past, present and future (2002) Nature Rev. Cancer, 2, pp. 143-148; Mohana, K., Purushothaman, K.K., Susan, T., Drug potential of echitamine chloride in cancer chemotherapy (1985) Bulletin Medico-Ethno-Botanical Res., 6, pp. 124-132; Moron, M.S., Depierre, J.W., Mannervik, B., Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver (1979) Biochim. Biophys. Acta, 582, pp. 67-78; Nadkarni, A.K., (1976) Indian Materia Medica. 3rd Edn., , Popular Press Ltd, Mumbai, India; Nias, A.H.W., Radiation biology (1990) Treatment of Cancer, pp. 53-75. , Sikora, K., Halnan, K. E. (eds). Chapman and Hall Medical, London; Pezzuto, J.M., Plant-derived anticancer agents (1997) Biochem. Pharmacol., 53, pp. 121-133; Pratt, R.M., Willis, W.D., In vitro screening assay for teratogens using growth inhibition of human embryonic cells (1985) Proc. Natl. Acad. Sci. USA, 82, pp. 5791-5794; Quetin-Leclercq, J., Bouzahzah, B., Pons, A., Greimers, R., Angenot, L., Bassleer, R., Barbason, H., Strychnopentamine, a potential anticancer agent (1993) Planta Med., 59, pp. 59-62; Rajic, A., Kweifio-Okai, G., Macrides, T., Sandeman, R.M., Chandler, D.S., Polya, G.M., Inhibition of serine proteases by anti-inflammatory triterpenoids (2000) Planta Med., 66, pp. 206-210; Ramirez, A., Garcia-Rubio, S., Current progress in the chemistry and pharmacology of akuammiline alkaloids (2003) Curr. Med. Chem., 10, pp. 1891-1915; Saraswathi, V., Ramamurthy, N., Subramanian, S., Mathuram, V., Govindasamy, S., Enhancement of the cytotoxic effects of echitamine chloride by vitamin A: An in vitro study on Ehrlich ascites carcinoma cell culture (1997) Ind. J. Pharmacol., 29, pp. 244-249; Saraswathi, V., Ramamoorthy, N., Subramaniam, S., Mathuram, V., Gunasekaran, P., Govindasamy, S., Inhibition of glycolysis and respiration of sarcoma-180 cells by echitamine chloride (1998) Chemotherapy, 44, pp. 198-205; Saraswathi, V., Shyamala, A.C., Subramanian, S., Govindasamy, S., Mathuram, V., Studies on the effect of echitamine chloride on serum glycoproteins and lysosomal hydrolases of sarcoma-180 induced mice (1998) Fitoterapia, 1, pp. 73-76; Satyavati, G.V., Gupta, A.K., Tandon, N., (1987) Medicinal Plants of India, 2, pp. 230-239. , Indian Council of Medical Research, New Delhi, India; Sharada, A.C., Solomon, F.E., Devi, P.U., Udupa, N., Srinivasan, K.K., Antitumor and radiosensitizing effects of withaferin a on mouse Ehrlich ascites carcinoma in vivo (1996) Acta Oncol., 35, pp. 95-100; Uma Devi, P., Solomon, F.E., Sharada, A.C., Plumbagin, a plant naphthoquinone with antitumor and radiomodifying properties (1999) Pharmaceut. Biol., 37, pp. 231-236; Warrier, P.K., Nambiar, V.P.K., Ramankutty, C., (1996) Indian Medicinal Plants, pp. 1-5. , Orient Longman Limited, Hyderbad, India

PY - 2005

Y1 - 2005

N2 - 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 (EAQ. 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 mgkg-1) caused toxicity in the recipient mice, therefore 12 mgkg-1 was considered the best cytotoxic dose for its anti-tumour effect. Administration of 12 mgkg-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 mgkg-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. © 2005 The Authors.

AB - 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 (EAQ. 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 mgkg-1) caused toxicity in the recipient mice, therefore 12 mgkg-1 was considered the best cytotoxic dose for its anti-tumour effect. Administration of 12 mgkg-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 mgkg-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. © 2005 The Authors.

U2 - 10.1211/jpp.57.9.0017

DO - 10.1211/jpp.57.9.0017

M3 - Article

VL - 57

SP - 1213

EP - 1219

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 9

ER -