Therapeutic effect of anthracene-based anticancer agent ethonafide in an animal model of multiple sclerosis

Wen Hua Piao, Rudy Wong, Xue Feng Bai, Jianhua Huang, Denise I. Campagnolo, Robert T Dorr, Timothy L. Vollmer, Fu Dong Shi

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The side effects of cancer chemotherapeutic agents such as mitoxantrone (MIT) in multiple sclerosis (MS) patients justify the search for less toxic drugs. Ethonafide is an anthracene-based antineoplastic drug similar to MIT. With reference to MIT, we examined the effect of ethonafide on experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, an animal model of human MS. We demonstrated that ethonafide is effective in preventing development of EAE as well as in ameliorating the severity of EAE when disease is ongoing. In relatively higher dosages, the effects of ethonafide and MIT on EAE were identical, whereas in lower dosages, MIT seemed more effective. Therapeutic effects of ethonafide were associated with the initial reduction in cellular counts of CD3+, CD4+, CD8+, B220+, CD11b+, NK cells, and NKT cells, followed by recovery of these cells from the bone marrow. Interestingly, the recovered autoreactive T cells in ethonafide-treated animals have reduced capacity to expand and produce cytokines in response to myelin Ag stimulation. Furthermore, CD4+CD25 + regulatory T cells were relatively resistant to depletion and/or recovered faster than T effector cells. The ability of regulatory T cells to resist depletion and replenish quickly during cell ablation therapy may provide an opportunity to reprogram the immune system. Moreover, we provided evidences that ethonafide has less cardiac toxicity compared with MIT. The effectiveness and the low cardiotoxicity of ethonafide might make it a promising immunosuppressive agent for clinical use in treating MS patients.

Original languageEnglish (US)
Pages (from-to)7415-7423
Number of pages9
JournalJournal of Immunology
Volume179
Issue number11
StatePublished - Dec 1 2007

Fingerprint

Therapeutic Uses
Antineoplastic Agents
Mitoxantrone
Multiple Sclerosis
Animal Models
Autoimmune Experimental Encephalomyelitis
Regulatory T-Lymphocytes
Natural Killer T-Cells
2-(2'-(dimethylamino)ethyl)-1,2-dihydro-7-ethoxydibenz(de,h)isoquinoline-1,3-dione
anthracene
Poisons
Immunosuppressive Agents
CD4 Lymphocyte Count
Myelin Sheath
Cell- and Tissue-Based Therapy
Inbred C57BL Mouse
Natural Killer Cells
Bone Marrow Cells
Immune System
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Piao, W. H., Wong, R., Bai, X. F., Huang, J., Campagnolo, D. I., Dorr, R. T., ... Shi, F. D. (2007). Therapeutic effect of anthracene-based anticancer agent ethonafide in an animal model of multiple sclerosis. Journal of Immunology, 179(11), 7415-7423.

Therapeutic effect of anthracene-based anticancer agent ethonafide in an animal model of multiple sclerosis. / Piao, Wen Hua; Wong, Rudy; Bai, Xue Feng; Huang, Jianhua; Campagnolo, Denise I.; Dorr, Robert T; Vollmer, Timothy L.; Shi, Fu Dong.

In: Journal of Immunology, Vol. 179, No. 11, 01.12.2007, p. 7415-7423.

Research output: Contribution to journalArticle

Piao, WH, Wong, R, Bai, XF, Huang, J, Campagnolo, DI, Dorr, RT, Vollmer, TL & Shi, FD 2007, 'Therapeutic effect of anthracene-based anticancer agent ethonafide in an animal model of multiple sclerosis', Journal of Immunology, vol. 179, no. 11, pp. 7415-7423.
Piao, Wen Hua ; Wong, Rudy ; Bai, Xue Feng ; Huang, Jianhua ; Campagnolo, Denise I. ; Dorr, Robert T ; Vollmer, Timothy L. ; Shi, Fu Dong. / Therapeutic effect of anthracene-based anticancer agent ethonafide in an animal model of multiple sclerosis. In: Journal of Immunology. 2007 ; Vol. 179, No. 11. pp. 7415-7423.
@article{29d072d5baee421e94d803d31b0e4833,
title = "Therapeutic effect of anthracene-based anticancer agent ethonafide in an animal model of multiple sclerosis",
abstract = "The side effects of cancer chemotherapeutic agents such as mitoxantrone (MIT) in multiple sclerosis (MS) patients justify the search for less toxic drugs. Ethonafide is an anthracene-based antineoplastic drug similar to MIT. With reference to MIT, we examined the effect of ethonafide on experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, an animal model of human MS. We demonstrated that ethonafide is effective in preventing development of EAE as well as in ameliorating the severity of EAE when disease is ongoing. In relatively higher dosages, the effects of ethonafide and MIT on EAE were identical, whereas in lower dosages, MIT seemed more effective. Therapeutic effects of ethonafide were associated with the initial reduction in cellular counts of CD3+, CD4+, CD8+, B220+, CD11b+, NK cells, and NKT cells, followed by recovery of these cells from the bone marrow. Interestingly, the recovered autoreactive T cells in ethonafide-treated animals have reduced capacity to expand and produce cytokines in response to myelin Ag stimulation. Furthermore, CD4+CD25 + regulatory T cells were relatively resistant to depletion and/or recovered faster than T effector cells. The ability of regulatory T cells to resist depletion and replenish quickly during cell ablation therapy may provide an opportunity to reprogram the immune system. Moreover, we provided evidences that ethonafide has less cardiac toxicity compared with MIT. The effectiveness and the low cardiotoxicity of ethonafide might make it a promising immunosuppressive agent for clinical use in treating MS patients.",
author = "Piao, {Wen Hua} and Rudy Wong and Bai, {Xue Feng} and Jianhua Huang and Campagnolo, {Denise I.} and Dorr, {Robert T} and Vollmer, {Timothy L.} and Shi, {Fu Dong}",
year = "2007",
month = "12",
day = "1",
language = "English (US)",
volume = "179",
pages = "7415--7423",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "11",

}

TY - JOUR

T1 - Therapeutic effect of anthracene-based anticancer agent ethonafide in an animal model of multiple sclerosis

AU - Piao, Wen Hua

AU - Wong, Rudy

AU - Bai, Xue Feng

AU - Huang, Jianhua

AU - Campagnolo, Denise I.

AU - Dorr, Robert T

AU - Vollmer, Timothy L.

AU - Shi, Fu Dong

PY - 2007/12/1

Y1 - 2007/12/1

N2 - The side effects of cancer chemotherapeutic agents such as mitoxantrone (MIT) in multiple sclerosis (MS) patients justify the search for less toxic drugs. Ethonafide is an anthracene-based antineoplastic drug similar to MIT. With reference to MIT, we examined the effect of ethonafide on experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, an animal model of human MS. We demonstrated that ethonafide is effective in preventing development of EAE as well as in ameliorating the severity of EAE when disease is ongoing. In relatively higher dosages, the effects of ethonafide and MIT on EAE were identical, whereas in lower dosages, MIT seemed more effective. Therapeutic effects of ethonafide were associated with the initial reduction in cellular counts of CD3+, CD4+, CD8+, B220+, CD11b+, NK cells, and NKT cells, followed by recovery of these cells from the bone marrow. Interestingly, the recovered autoreactive T cells in ethonafide-treated animals have reduced capacity to expand and produce cytokines in response to myelin Ag stimulation. Furthermore, CD4+CD25 + regulatory T cells were relatively resistant to depletion and/or recovered faster than T effector cells. The ability of regulatory T cells to resist depletion and replenish quickly during cell ablation therapy may provide an opportunity to reprogram the immune system. Moreover, we provided evidences that ethonafide has less cardiac toxicity compared with MIT. The effectiveness and the low cardiotoxicity of ethonafide might make it a promising immunosuppressive agent for clinical use in treating MS patients.

AB - The side effects of cancer chemotherapeutic agents such as mitoxantrone (MIT) in multiple sclerosis (MS) patients justify the search for less toxic drugs. Ethonafide is an anthracene-based antineoplastic drug similar to MIT. With reference to MIT, we examined the effect of ethonafide on experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, an animal model of human MS. We demonstrated that ethonafide is effective in preventing development of EAE as well as in ameliorating the severity of EAE when disease is ongoing. In relatively higher dosages, the effects of ethonafide and MIT on EAE were identical, whereas in lower dosages, MIT seemed more effective. Therapeutic effects of ethonafide were associated with the initial reduction in cellular counts of CD3+, CD4+, CD8+, B220+, CD11b+, NK cells, and NKT cells, followed by recovery of these cells from the bone marrow. Interestingly, the recovered autoreactive T cells in ethonafide-treated animals have reduced capacity to expand and produce cytokines in response to myelin Ag stimulation. Furthermore, CD4+CD25 + regulatory T cells were relatively resistant to depletion and/or recovered faster than T effector cells. The ability of regulatory T cells to resist depletion and replenish quickly during cell ablation therapy may provide an opportunity to reprogram the immune system. Moreover, we provided evidences that ethonafide has less cardiac toxicity compared with MIT. The effectiveness and the low cardiotoxicity of ethonafide might make it a promising immunosuppressive agent for clinical use in treating MS patients.

UR - http://www.scopus.com/inward/record.url?scp=38849159198&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38849159198&partnerID=8YFLogxK

M3 - Article

C2 - 18025185

AN - SCOPUS:38849159198

VL - 179

SP - 7415

EP - 7423

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -