Effect of artesunate on immune cells in ret-transgenic mouse melanoma model

Autoren

Marcel Ramacher
Viktor Umansky
Thomas Efferth

DOI

10.1097/cad.0b013e328330caba

ISSN

0959-4973

Ausgabe der Veröffentlichung

10

Zeitschrift

Anti-Cancer Drugs

Sprache

en

Paginierung

910 - 917

Datum der Veröffentlichung

2009

Status

Published

Herausgeber

Ovid Technologies (Wolters Kluwer Health)

Herausgeber URL

http://dx.doi.org/10.1097/cad.0b013e328330caba

Datum der Datenerfassung

2021

Titel

Effect of artesunate on immune cells in ret-transgenic mouse melanoma model

Ausgabe der Zeitschrift

20

Data source: Crossref

Abstract

The antimalarial artesunate also exerts profound cytotoxicity toward tumor cells. Earlier investigations controversially discussed a possible immunosuppressive function of artemsinin and its derivatives. This poses the question, whether immunosuppressive activity counteracts the anticancer activity in vivo. To clarify this issue, we used a transgenic mouse spontaneous melanoma model, in which ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. ret-transgenic mice were previously reported to accumulate melanoma-specific effector memory T cells and natural killer (NK) cells in the primary tumors and metastatic lymph nodes. In the present investigation, we monitored effects of artesunate on the CD4 and CD8 T cells as well as Treg and NK cells from ret-transgenic tumor-bearing mice and nontransgenic littermates in vivo. In addition, we investigated cytostatic and cytotoxic activity of artesunate on ret-tumor cells established from the mouse primary tumor. Artesunate inhibited growth of ret-tumor cells and induces their apoptosis in a concentration-dependent manner (0.1-200 micromol/l). Furthermore, we did not find considerable effects of artesunate on the immune function as measured by major cell populations of the immune system; that is, CD4 and CD8 T cells as well as Treg and NK cells both from ret-transgenic mice and nontransgenic C57BL/6 littermates treated for 2 weeks with a daily dose of 1 mg artesunate. These results indicate that the cytostatic and apoptotic effects of artesunate are not diminished by concomitant immunosuppression.

Addresses

German Cancer Research Center, Skin Cancer Unit (G300), Im Neuenheimer Feld, Heidelberg, Germany.

Autoren

Marcel Ramacher
Viktor Umansky
Thomas Efferth
Thomas Efferth

DOI

10.1097/cad.0b013e328330caba

eISSN

1473-5741

Externe Identifier

PubMed Identifier: 19745721

Open access

false

ISSN

0959-4973

Ausgabe der Veröffentlichung

10

Zeitschrift

Anti-cancer drugs

Schlüsselwörter

Killer Cells, Natural
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cell Line, Tumor
Animals
Mice, Inbred C57BL
Mice, Transgenic
Mice
Melanoma, Experimental
Skin Neoplasms
Artemisinins
Antineoplastic Agents
Apoptosis
T-Lymphocytes, Regulatory
Proto-Oncogene Proteins c-ret
Artesunate

Sprache

eng

Medium

Print

Paginierung

910 - 917

Datum der Veröffentlichung

2009

Status

Published

Datum der Datenerfassung

2009

Titel

Effect of artesunate on immune cells in ret-transgenic mouse melanoma model.

Sub types

Journal Article

Ausgabe der Zeitschrift

20

Data source: Europe PubMed Central

Abstract

The antimalarial artesunate also exerts profound cytotoxicity toward tumor cells. Earlier investigations controversially discussed a possible immunosuppressive function of artemsinin and its derivatives. This poses the question, whether immunosuppressive activity counteracts the anticancer activity in vivo. To clarify this issue, we used a transgenic mouse spontaneous melanoma model, in which ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. ret-transgenic mice were previously reported to accumulate melanoma-specific effector memory T cells and natural killer (NK) cells in the primary tumors and metastatic lymph nodes. In the present investigation, we monitored effects of artesunate on the CD4 and CD8 T cells as well as Treg and NK cells from ret-transgenic tumor-bearing mice and nontransgenic littermates in vivo. In addition, we investigated cytostatic and cytotoxic activity of artesunate on ret-tumor cells established from the mouse primary tumor. Artesunate inhibited growth of ret-tumor cells and induces their apoptosis in a concentration-dependent manner (0.1-200 micromol/l). Furthermore, we did not find considerable effects of artesunate on the immune function as measured by major cell populations of the immune system; that is, CD4 and CD8 T cells as well as Treg and NK cells both from ret-transgenic mice and nontransgenic C57BL/6 littermates treated for 2 weeks with a daily dose of 1 mg artesunate. These results indicate that the cytostatic and apoptotic effects of artesunate are not diminished by concomitant immunosuppression.

Autoren

Marcel Ramacher
Viktor Umansky
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/19745721

DOI

10.1097/CAD.0b013e328330caba

eISSN

1473-5741

Ausgabe der Veröffentlichung

10

Zeitschrift

Anticancer Drugs

Schlüsselwörter

Animals
Antineoplastic Agents
Apoptosis
Artemisinins
Artesunate
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cell Line, Tumor
Killer Cells, Natural
Melanoma, Experimental
Mice
Mice, Inbred C57BL
Mice, Transgenic
Proto-Oncogene Proteins c-ret
Skin Neoplasms
T-Lymphocytes, Regulatory

Sprache

eng

Country

England

Paginierung

910 - 917

Datum der Veröffentlichung

2009

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2009

Titel

Effect of artesunate on immune cells in ret-transgenic mouse melanoma model.

Sub types

Journal Article

Ausgabe der Zeitschrift

20

Data source: PubMed

Effect of artesunate on immune cells in ret-transgenic mouse melanoma model

Tools