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Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer.
Biomed Pharmacother. 2010 Nov; 64(9):609-14.BP

Abstract

Metastatic breast cancers are hard to treat and almost always fatal. Chloroquine diphosphate, a derivative of quinine, has long been used as a potent and commonly used medicine against different human diseases. We therefore investigated the effects of chloroquine diphosphate on a highly metastatic mouse mammary carcinoma cell line. In vitro treatment of 4T1 mouse breast cancer cells with chloroquine diphosphate resulted in significant inhibition of cellular proliferation and viability, and induction of apoptosis in 4T1 cells in a time- and dose-dependent manner. Further analysis indicated that induction of apoptosis was associated with the loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-9 and caspase-3, and cleavage of poly(ADP-ribose) polymerase. The effect of chloroquine diphosphate was then examined using a mice model in which 4T1 cells were implanted subcutaneously. Chloroquine diphosphate (25mg/kg and 50mg/kg, respectively) significantly inhibited the growth of the implanted 4T1 tumor cells and induced apoptosis in the tumor microenvironment. Moreover, the metastasis of tumor cells to the lungs was inhibited significantly and the survival of the mice enhanced. These data suggested that chloroquine diphosphate might have chemotherapeutic efficacy against breast cancer including inhibition of metastasis.

Authors+Show Affiliations

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, No. 1 Keyuan Road 4, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan 610041, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20888174

Citation

Jiang, Pei-Du, et al. "Antitumor and Antimetastatic Activities of Chloroquine Diphosphate in a Murine Model of Breast Cancer." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 64, no. 9, 2010, pp. 609-14.
Jiang PD, Zhao YL, Deng XQ, et al. Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer. Biomed Pharmacother. 2010;64(9):609-14.
Jiang, P. D., Zhao, Y. L., Deng, X. Q., Mao, Y. Q., Shi, W., Tang, Q. Q., Li, Z. G., Zheng, Y. Z., Yang, S. Y., & Wei, Y. Q. (2010). Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 64(9), 609-14. https://doi.org/10.1016/j.biopha.2010.06.004
Jiang PD, et al. Antitumor and Antimetastatic Activities of Chloroquine Diphosphate in a Murine Model of Breast Cancer. Biomed Pharmacother. 2010;64(9):609-14. PubMed PMID: 20888174.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antitumor and antimetastatic activities of chloroquine diphosphate in a murine model of breast cancer. AU - Jiang,Pei-Du, AU - Zhao,Ying-Lan, AU - Deng,Xiao-Qiang, AU - Mao,Yong-Qiu, AU - Shi,Wei, AU - Tang,Qing-Qing, AU - Li,Zheng-Guang, AU - Zheng,Yu-Zhu, AU - Yang,Sheng-Yong, AU - Wei,Yu-Quan, PY - 2010/04/15/received PY - 2010/06/21/accepted PY - 2010/10/5/entrez PY - 2010/10/5/pubmed PY - 2011/3/3/medline SP - 609 EP - 14 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 64 IS - 9 N2 - Metastatic breast cancers are hard to treat and almost always fatal. Chloroquine diphosphate, a derivative of quinine, has long been used as a potent and commonly used medicine against different human diseases. We therefore investigated the effects of chloroquine diphosphate on a highly metastatic mouse mammary carcinoma cell line. In vitro treatment of 4T1 mouse breast cancer cells with chloroquine diphosphate resulted in significant inhibition of cellular proliferation and viability, and induction of apoptosis in 4T1 cells in a time- and dose-dependent manner. Further analysis indicated that induction of apoptosis was associated with the loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-9 and caspase-3, and cleavage of poly(ADP-ribose) polymerase. The effect of chloroquine diphosphate was then examined using a mice model in which 4T1 cells were implanted subcutaneously. Chloroquine diphosphate (25mg/kg and 50mg/kg, respectively) significantly inhibited the growth of the implanted 4T1 tumor cells and induced apoptosis in the tumor microenvironment. Moreover, the metastasis of tumor cells to the lungs was inhibited significantly and the survival of the mice enhanced. These data suggested that chloroquine diphosphate might have chemotherapeutic efficacy against breast cancer including inhibition of metastasis. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/20888174/Antitumor_and_antimetastatic_activities_of_chloroquine_diphosphate_in_a_murine_model_of_breast_cancer_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(10)00117-4 DB - PRIME DP - Unbound Medicine ER -