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Article

Chloroquine has tumor‑inhibitory and tumor‑promoting effects in triple‑negative breast cancer

  • Authors:
    • Johanna Tuomela
    • Jouko Sandholm
    • Joonas H. Kauppila
    • Petri Lehenkari
    • Kevin W. Harris
    • Katri S. Selander
  • View Affiliations / Copyright

    Affiliations: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA, Department of Anatomy and Cell Biology, University of Oulu, Oulu 90014, Finland
  • Pages: 1665-1672
    |
    Published online on: October 4, 2013
       https://doi.org/10.3892/ol.2013.1602
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Abstract

Toll‑like receptor‑9 (TLR9) is an intracellular DNA receptor that is widely expressed in breast and other cancers. We previously demonstrated that low tumor TLR9 expression upon diagnosis is associated with significantly shortened disease‑specific survival times in patients with triple‑negative breast cancer (TNBC). There are no targeted therapies for this subgroup of patients whose prognosis is among the worst in breast cancer. Due to the previously detected in vitro anti‑invasive effects of chloroquine in these cell lines, the present study aimed to investigate the in vivo effects of chloroquine against two clinical subtypes of TNBC that differ in TLR9 expression. Chloroquine suppressed matrix metalloproteinase (MMP)‑2 and MMP‑9 mRNA expression and protein activity, whereas MMP‑13 mRNA expression and proteolytic activity were increased. Despite enhancing TLR9 mRNA expression, chloroquine suppressed TLR9 protein expression in vitro. Daily treatment of mice with intraperitoneal (i.p.) chloroquine (80 mg/kg/day) for 22 days, did not inhibit the growth of control siRNA or TLR9 siRNA MDA‑MB‑231 breast cancer cells. In conclusion, despite the favorable in vitro effects on TNBC invasion and viability, particularly in hypoxic conditions, chloroquine does not prevent the growth of the triple‑negative MDA‑MB‑231 cells with high or low TLR9 expression levels in vivo. This may be explained by the activating effects of chloroquine on MMP‑13 expression or by the fact that chloroquine, by suppressing TLR9 expression, permits the activation of currently unknown molecular pathways, which allow the aggressive behavior of TNBC cells with low TLR9 expression in hypoxia.
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Copy and paste a formatted citation
Spandidos Publications style
Tuomela J, Sandholm J, Kauppila JH, Lehenkari P, Harris KW and Selander KS: Chloroquine has tumor‑inhibitory and tumor‑promoting effects in triple‑negative breast cancer. Oncol Lett 6: 1665-1672, 2013.
APA
Tuomela, J., Sandholm, J., Kauppila, J.H., Lehenkari, P., Harris, K.W., & Selander, K.S. (2013). Chloroquine has tumor‑inhibitory and tumor‑promoting effects in triple‑negative breast cancer. Oncology Letters, 6, 1665-1672. https://doi.org/10.3892/ol.2013.1602
MLA
Tuomela, J., Sandholm, J., Kauppila, J. H., Lehenkari, P., Harris, K. W., Selander, K. S."Chloroquine has tumor‑inhibitory and tumor‑promoting effects in triple‑negative breast cancer". Oncology Letters 6.6 (2013): 1665-1672.
Chicago
Tuomela, J., Sandholm, J., Kauppila, J. H., Lehenkari, P., Harris, K. W., Selander, K. S."Chloroquine has tumor‑inhibitory and tumor‑promoting effects in triple‑negative breast cancer". Oncology Letters 6, no. 6 (2013): 1665-1672. https://doi.org/10.3892/ol.2013.1602
Copy and paste a formatted citation
x
Spandidos Publications style
Tuomela J, Sandholm J, Kauppila JH, Lehenkari P, Harris KW and Selander KS: Chloroquine has tumor‑inhibitory and tumor‑promoting effects in triple‑negative breast cancer. Oncol Lett 6: 1665-1672, 2013.
APA
Tuomela, J., Sandholm, J., Kauppila, J.H., Lehenkari, P., Harris, K.W., & Selander, K.S. (2013). Chloroquine has tumor‑inhibitory and tumor‑promoting effects in triple‑negative breast cancer. Oncology Letters, 6, 1665-1672. https://doi.org/10.3892/ol.2013.1602
MLA
Tuomela, J., Sandholm, J., Kauppila, J. H., Lehenkari, P., Harris, K. W., Selander, K. S."Chloroquine has tumor‑inhibitory and tumor‑promoting effects in triple‑negative breast cancer". Oncology Letters 6.6 (2013): 1665-1672.
Chicago
Tuomela, J., Sandholm, J., Kauppila, J. H., Lehenkari, P., Harris, K. W., Selander, K. S."Chloroquine has tumor‑inhibitory and tumor‑promoting effects in triple‑negative breast cancer". Oncology Letters 6, no. 6 (2013): 1665-1672. https://doi.org/10.3892/ol.2013.1602
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