A comparison of low-dose cyclophosphamide treatment with artemisinin treatment in reducing the number of regulatory T cells in murine breast cancer model

• Published in: International immunopharmacology 2010-09, Vol.10 (9), p.1055-1061
• Main Authors: Langroudi, Ladan, Hassan, Zuhir Muhammad, Ebtekar, Massoumeh, Mahdavi, Mehdi, Pakravan, Nafise, Noori, Shokoofe
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Neoplasm - analysis; Antibodies, Neoplasm - immunology; Antineoplastic Agents - immunology; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Artemisinin; Artemisinins - immunology; Artemisinins - pharmacology; Artemisinins - therapeutic use; Biological and medical sciences; Breast cancer; Carcinoma, Ductal, Breast - drug therapy; Carcinoma, Ductal, Breast - immunology; Cyclophosphamide; Cyclophosphamide - immunology; Cyclophosphamide - pharmacology; Cyclophosphamide - therapeutic use; Female; Gynecology. Andrology. Obstetrics; Interferon-gamma - analysis; Interleukin-4 - analysis; Mammary gland diseases; Mammary Neoplasms, Experimental - drug therapy; Mammary Neoplasms, Experimental - immunology; Medical sciences; Mice; Mice, Inbred BALB C; Pharmacology. Drug treatments; Regulatory T cells; Spleen - drug effects; Spleen - immunology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Tumors
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2010.06.005

Artemisinin (ART) is a sesquiterpene lactone. Possessing an endoperoxide bridge is unique among ant-imalarial drugs, and now much attention is focused on the anti-cancer properties of ART. In this study we aimed at the immunomodulatory effects of artemisinin in the treatment of breast cancer in comparison to the conventional anti-cancer drug, cyclophasphamide (CTX). We examined delayed-type hypersensitivity, antibody and IL-4 and IFNγ production, tumour volume, tumour infiltrated regulatory T cells (Treg) and spleen lymphocyte proliferation assay. Briefly three groups of five 4–6 week old female Balb/c tumour-bearing mice (mouse mammary tumour) were treated with 2.8 mg/kg ART and 20 mg/kg CTX intraperitoneally for 20 consecutive days. Tumour volume was measured using a digital vernier calliper (with accuracy of 0.01). Mice were sacrificed and percentage of tumour infiltrating Tregs were obtained using flow cytometry (BD, USA). Proliferation of splenocytes was obtained using BrdU proliferation assay (Roche). Our results showed that ART can reduce the number of Tregs in tumour stroma (P-value ≤ 0.047) as compared to CTX (P-value ≥ 0.05) and control. Furthermore ART increased IFNγ/IL-4 ratio produced in splenocyte culture (P-value ≤ 0.001). Proliferation assay did not show any significant difference (P-value ≥ 0.05). Cancer is a multi-factorial disease which needs a multi-approach treatment. Early accumulation of Treg cells in the tumour tissue correlates with tumour progression and is an indication of bad prognosis. According to the obtained results, ART can reduce the number of Tregs. We suggest using artemisinin, with its dual action mechanism. It can effectively kill cancer cells along with reducing the suppressive microenvironment.