Cytotoxicity of Mahanimbine, Murryafoline A and S-Benzyldithiocarbazate on Human Leukemic Cell Line, CEM-SS

Mahanimbine, a carbazole alkaloid was isolated from an ether extract of the stem bark of Murraya koenigii whilst Murrayafoline A was isolated from petroleum ether extract of the roots of Murraya koenigii. S-Benzyldithiocarbazate is a dithiocarbazic acid Schiff base derived from S-alkyl esters. Th...

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Main Author: Kok, Yih Yih
Format: Thesis
Language:English
English
Published: 2001
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Online Access:http://psasir.upm.edu.my/id/eprint/8432/1/FSMB_2001_5_IR.pdf
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spelling my-upm-ir.84322024-01-16T02:09:17Z Cytotoxicity of Mahanimbine, Murryafoline A and S-Benzyldithiocarbazate on Human Leukemic Cell Line, CEM-SS 2001-12 Kok, Yih Yih Mahanimbine, a carbazole alkaloid was isolated from an ether extract of the stem bark of Murraya koenigii whilst Murrayafoline A was isolated from petroleum ether extract of the roots of Murraya koenigii. S-Benzyldithiocarbazate is a dithiocarbazic acid Schiff base derived from S-alkyl esters. They were found to exhibit cytotoxic activity against CEM-SS human T-lymphoblastic leukemic cells. The cytotoxic activity of Mahanimbine, Murrayafoline A and S-Benzyldithiocarbazate that inhibit 50 % growth (IC₅₀) of CEM-SS were 6 µg/ml, S µg/ml and 7.S µg/ml respectively. For comparative purposes, the IC₅₀ of several commercial cytotoxic drugs against CEM-SS were determined. The inhibition effect of Mahanimbine, Murrayafoline A and SBenzyldithiocarbazate were better than Methotrexate (IC₅₀ > 30 µg/ml), Doxorubicine (IC₅₀ = 21 µg/ml), Cytarabine (IC₅₀ > 30 µg/ml) and Colchecine (IC₅₀ = 8 µg/ml).These compounds were found to be less active than cis-diamine dichloroplatinwn and Vinorelbine tartrate with a IC₅₀ value of 3 µg/ml. In contrast, these three compounds were found to be less active against normal mouse fibroblasts cell, 3T3 with the IC₅₀ value of 11 µg/ml (Mahanimbine), 17 µg/ml (Murrayafoline A) and 10 µg/ml (SBenzyldithiocarbazate) respectively. The study showed that the proliferation of cells was inhibited before the cells were being killed. In addition, Mahanimbine, MurrayafolineA and S-Benzyldithiocarbazate caused programmed cell death by showing apoptotic features such as nucleus fragmentation, cell shrinkage, membrane blebbing and formation of apoptotic bodies. These were further confirmed with DNA laddering in agarose gel electrophoresis assay due to DNA fragmentation. DNA laddering was obtained after 24 hours of treatment by these three compounds in a doseindependent but time-dependent way. Mahanimbine and Murrayafoline A were shown to arrest CEM-SS cells at G1 phase of cell cycle using flowcytometry method. As a result, Mahanimbine, Murrayafoline A and S-Benzyldithiocarbazate were found as potent antitumor agents. Antibody-dependent cell cytotoxicity Antineoplastic agents 2001-12 Thesis http://psasir.upm.edu.my/id/eprint/8432/ http://psasir.upm.edu.my/id/eprint/8432/1/FSMB_2001_5_IR.pdf text en public masters Universiti Putra Malaysia Antibody-dependent cell cytotoxicity Antineoplastic agents Food Science and Technology Ali, Abdul Manaf English
institution Universiti Putra Malaysia
collection PSAS Institutional Repository
language English
English
advisor Ali, Abdul Manaf
topic Antibody-dependent cell cytotoxicity
Antineoplastic agents

spellingShingle Antibody-dependent cell cytotoxicity
Antineoplastic agents

Kok, Yih Yih
Cytotoxicity of Mahanimbine, Murryafoline A and S-Benzyldithiocarbazate on Human Leukemic Cell Line, CEM-SS
description Mahanimbine, a carbazole alkaloid was isolated from an ether extract of the stem bark of Murraya koenigii whilst Murrayafoline A was isolated from petroleum ether extract of the roots of Murraya koenigii. S-Benzyldithiocarbazate is a dithiocarbazic acid Schiff base derived from S-alkyl esters. They were found to exhibit cytotoxic activity against CEM-SS human T-lymphoblastic leukemic cells. The cytotoxic activity of Mahanimbine, Murrayafoline A and S-Benzyldithiocarbazate that inhibit 50 % growth (IC₅₀) of CEM-SS were 6 µg/ml, S µg/ml and 7.S µg/ml respectively. For comparative purposes, the IC₅₀ of several commercial cytotoxic drugs against CEM-SS were determined. The inhibition effect of Mahanimbine, Murrayafoline A and SBenzyldithiocarbazate were better than Methotrexate (IC₅₀ > 30 µg/ml), Doxorubicine (IC₅₀ = 21 µg/ml), Cytarabine (IC₅₀ > 30 µg/ml) and Colchecine (IC₅₀ = 8 µg/ml).These compounds were found to be less active than cis-diamine dichloroplatinwn and Vinorelbine tartrate with a IC₅₀ value of 3 µg/ml. In contrast, these three compounds were found to be less active against normal mouse fibroblasts cell, 3T3 with the IC₅₀ value of 11 µg/ml (Mahanimbine), 17 µg/ml (Murrayafoline A) and 10 µg/ml (SBenzyldithiocarbazate) respectively. The study showed that the proliferation of cells was inhibited before the cells were being killed. In addition, Mahanimbine, MurrayafolineA and S-Benzyldithiocarbazate caused programmed cell death by showing apoptotic features such as nucleus fragmentation, cell shrinkage, membrane blebbing and formation of apoptotic bodies. These were further confirmed with DNA laddering in agarose gel electrophoresis assay due to DNA fragmentation. DNA laddering was obtained after 24 hours of treatment by these three compounds in a doseindependent but time-dependent way. Mahanimbine and Murrayafoline A were shown to arrest CEM-SS cells at G1 phase of cell cycle using flowcytometry method. As a result, Mahanimbine, Murrayafoline A and S-Benzyldithiocarbazate were found as potent antitumor agents.
format Thesis
qualification_level Master's degree
author Kok, Yih Yih
author_facet Kok, Yih Yih
author_sort Kok, Yih Yih
title Cytotoxicity of Mahanimbine, Murryafoline A and S-Benzyldithiocarbazate on Human Leukemic Cell Line, CEM-SS
title_short Cytotoxicity of Mahanimbine, Murryafoline A and S-Benzyldithiocarbazate on Human Leukemic Cell Line, CEM-SS
title_full Cytotoxicity of Mahanimbine, Murryafoline A and S-Benzyldithiocarbazate on Human Leukemic Cell Line, CEM-SS
title_fullStr Cytotoxicity of Mahanimbine, Murryafoline A and S-Benzyldithiocarbazate on Human Leukemic Cell Line, CEM-SS
title_full_unstemmed Cytotoxicity of Mahanimbine, Murryafoline A and S-Benzyldithiocarbazate on Human Leukemic Cell Line, CEM-SS
title_sort cytotoxicity of mahanimbine, murryafoline a and s-benzyldithiocarbazate on human leukemic cell line, cem-ss
granting_institution Universiti Putra Malaysia
granting_department Food Science and Technology
publishDate 2001
url http://psasir.upm.edu.my/id/eprint/8432/1/FSMB_2001_5_IR.pdf
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