The Novel Heterocyclic Trioxirane [(1,3,5-Tris Oxiran-2-yl)Methyl)-1,3,5-Triazinane-2,4,6-Trione (TATT)] Exhibits a Better Anticancer Effect than Platinum-Based Chemotherapy by Induction of Apoptosis and Curcumin Further Enhances its Chemosensitivity

Chun-Li Su, Ying Ti Wang, Mu Hsin Chang, Kang Fang, Kwunmin Chen

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The heterocyclic trioxirane compound [1,3,5-tris((oxiran-2-yl)methyl)-1,3,5-triazinane-2,4,6-trione (TATT)] is a synthetic compound which has been used as an experimental anticancer agent in human clinical trials. Curcumin, an active natural compound in turmeric and curry, is an ingredient commonly used in the traditional diet of many Asian countries. In the present study, we observed that TATT exhibited a better anticancer effect on chemoresistant human colorectal cancer HT-29 cells and displayed less cytotoxicity on normal human umbilical vein endothelial cells, compared with FDA-approved anticancer drugs (cisplatin, carboplatin, or oxaliplatin) using MTT assay. TATT also induced a stronger apoptotic effect than that seen with the three studied anticancer drugs, as characterized by externalization of phosphatidylserine using flow cytometry. Administration of caspase 8-specific inhibitor (z-IETD-fmk) and mitochondrial permeability transition pore inhibitor (cyclosporin A) demonstrated that TATT-induced apoptosis proceeded via both extrinsic and intrinsic signaling pathways. It is noteworthy that coadministration of curcumin further significantly increased TATT-induced cytotoxicity, externalization of phosphatidylserine (representing early apoptosis), and the percentages of cells at the sub-G1 phase (representing late apoptosis), producing an additivity and/or synergistic effect, and vice versa. Suppression of nuclear NF-κB was involved in curcumin-enhanced chemosensitivity of TATT. Overall, our data indicate that TATT exerts a chemotherapeutic effect on colorectal cancer cells and coadministration of curcumin enhances the treatment effect of TATT.

Original languageEnglish
Pages (from-to)597-609
Number of pages13
JournalCell Biochemistry and Biophysics
Volume68
Issue number3
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

Induction Chemotherapy
Curcumin
Chemotherapy
Platinum
Apoptosis
oxaliplatin
Phosphatidylserines
Cytotoxicity
Colorectal Neoplasms
Heterocyclic Compounds
Curcuma
HT29 Cells
Flow cytometry
Caspase 8
Carboplatin
Endothelial cells
Human Umbilical Vein Endothelial Cells
G1 Phase
Nutrition
Pharmaceutical Preparations

Keywords

  • Carboplatin
  • Chemosensitivity
  • Cisplatin
  • Curcumin
  • Heterocyclic trioxiranes
  • Oxaliplatin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

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title = "The Novel Heterocyclic Trioxirane [(1,3,5-Tris Oxiran-2-yl)Methyl)-1,3,5-Triazinane-2,4,6-Trione (TATT)] Exhibits a Better Anticancer Effect than Platinum-Based Chemotherapy by Induction of Apoptosis and Curcumin Further Enhances its Chemosensitivity",
abstract = "The heterocyclic trioxirane compound [1,3,5-tris((oxiran-2-yl)methyl)-1,3,5-triazinane-2,4,6-trione (TATT)] is a synthetic compound which has been used as an experimental anticancer agent in human clinical trials. Curcumin, an active natural compound in turmeric and curry, is an ingredient commonly used in the traditional diet of many Asian countries. In the present study, we observed that TATT exhibited a better anticancer effect on chemoresistant human colorectal cancer HT-29 cells and displayed less cytotoxicity on normal human umbilical vein endothelial cells, compared with FDA-approved anticancer drugs (cisplatin, carboplatin, or oxaliplatin) using MTT assay. TATT also induced a stronger apoptotic effect than that seen with the three studied anticancer drugs, as characterized by externalization of phosphatidylserine using flow cytometry. Administration of caspase 8-specific inhibitor (z-IETD-fmk) and mitochondrial permeability transition pore inhibitor (cyclosporin A) demonstrated that TATT-induced apoptosis proceeded via both extrinsic and intrinsic signaling pathways. It is noteworthy that coadministration of curcumin further significantly increased TATT-induced cytotoxicity, externalization of phosphatidylserine (representing early apoptosis), and the percentages of cells at the sub-G1 phase (representing late apoptosis), producing an additivity and/or synergistic effect, and vice versa. Suppression of nuclear NF-κB was involved in curcumin-enhanced chemosensitivity of TATT. Overall, our data indicate that TATT exerts a chemotherapeutic effect on colorectal cancer cells and coadministration of curcumin enhances the treatment effect of TATT.",
keywords = "Carboplatin, Chemosensitivity, Cisplatin, Curcumin, Heterocyclic trioxiranes, Oxaliplatin",
author = "Chun-Li Su and Wang, {Ying Ti} and Chang, {Mu Hsin} and Kang Fang and Kwunmin Chen",
year = "2014",
month = "1",
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doi = "10.1007/s12013-013-9752-z",
language = "English",
volume = "68",
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T1 - The Novel Heterocyclic Trioxirane [(1,3,5-Tris Oxiran-2-yl)Methyl)-1,3,5-Triazinane-2,4,6-Trione (TATT)] Exhibits a Better Anticancer Effect than Platinum-Based Chemotherapy by Induction of Apoptosis and Curcumin Further Enhances its Chemosensitivity

AU - Su, Chun-Li

AU - Wang, Ying Ti

AU - Chang, Mu Hsin

AU - Fang, Kang

AU - Chen, Kwunmin

PY - 2014/1/1

Y1 - 2014/1/1

N2 - The heterocyclic trioxirane compound [1,3,5-tris((oxiran-2-yl)methyl)-1,3,5-triazinane-2,4,6-trione (TATT)] is a synthetic compound which has been used as an experimental anticancer agent in human clinical trials. Curcumin, an active natural compound in turmeric and curry, is an ingredient commonly used in the traditional diet of many Asian countries. In the present study, we observed that TATT exhibited a better anticancer effect on chemoresistant human colorectal cancer HT-29 cells and displayed less cytotoxicity on normal human umbilical vein endothelial cells, compared with FDA-approved anticancer drugs (cisplatin, carboplatin, or oxaliplatin) using MTT assay. TATT also induced a stronger apoptotic effect than that seen with the three studied anticancer drugs, as characterized by externalization of phosphatidylserine using flow cytometry. Administration of caspase 8-specific inhibitor (z-IETD-fmk) and mitochondrial permeability transition pore inhibitor (cyclosporin A) demonstrated that TATT-induced apoptosis proceeded via both extrinsic and intrinsic signaling pathways. It is noteworthy that coadministration of curcumin further significantly increased TATT-induced cytotoxicity, externalization of phosphatidylserine (representing early apoptosis), and the percentages of cells at the sub-G1 phase (representing late apoptosis), producing an additivity and/or synergistic effect, and vice versa. Suppression of nuclear NF-κB was involved in curcumin-enhanced chemosensitivity of TATT. Overall, our data indicate that TATT exerts a chemotherapeutic effect on colorectal cancer cells and coadministration of curcumin enhances the treatment effect of TATT.

AB - The heterocyclic trioxirane compound [1,3,5-tris((oxiran-2-yl)methyl)-1,3,5-triazinane-2,4,6-trione (TATT)] is a synthetic compound which has been used as an experimental anticancer agent in human clinical trials. Curcumin, an active natural compound in turmeric and curry, is an ingredient commonly used in the traditional diet of many Asian countries. In the present study, we observed that TATT exhibited a better anticancer effect on chemoresistant human colorectal cancer HT-29 cells and displayed less cytotoxicity on normal human umbilical vein endothelial cells, compared with FDA-approved anticancer drugs (cisplatin, carboplatin, or oxaliplatin) using MTT assay. TATT also induced a stronger apoptotic effect than that seen with the three studied anticancer drugs, as characterized by externalization of phosphatidylserine using flow cytometry. Administration of caspase 8-specific inhibitor (z-IETD-fmk) and mitochondrial permeability transition pore inhibitor (cyclosporin A) demonstrated that TATT-induced apoptosis proceeded via both extrinsic and intrinsic signaling pathways. It is noteworthy that coadministration of curcumin further significantly increased TATT-induced cytotoxicity, externalization of phosphatidylserine (representing early apoptosis), and the percentages of cells at the sub-G1 phase (representing late apoptosis), producing an additivity and/or synergistic effect, and vice versa. Suppression of nuclear NF-κB was involved in curcumin-enhanced chemosensitivity of TATT. Overall, our data indicate that TATT exerts a chemotherapeutic effect on colorectal cancer cells and coadministration of curcumin enhances the treatment effect of TATT.

KW - Carboplatin

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KW - Oxaliplatin

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