PMID: 25773848Mar 17, 2015Paper

Chloroquine exerts anti-metastatic activities under hypoxic conditions in cholangiocarcinoma cells

Asian Pacific Journal of Cancer Prevention : APJCP
Suyanee ThongchotNisana Namwat

Abstract

Intra-tumoral hypoxia is an environment that promotes tumor cell migration, angiogenesis and epithelial- mesenchymal transition that accounts for a major mechanism of metastasis. Chloroquine potentially offers a new therapeutic approach with an 'old' drug for effective and safe cancer therapies, as it exerts anti-metastatic activity. We investigated the inhibitory effect of chloroquine on cholangiocarcinoma (CCA) cell migration under cobalt chloride (CoCl2)-stimulated hypoxia. We showed that chloroquine suppressed CCA cell migration under hypoxic-mimicking conditions on exposure to 100 μM CoCl2. Moreover, chloroquine stabilized the protein level of prolyl hydroxylase domain proteins (PHD-2) but reduced the levels of hypoxic responsive proteins such as hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF). It also suppressed epithelial mesenchymal transition (EMT) by increasing the ratio of E-cadherin to N-cadherin under hypoxic conditions. In conclusion, chloroquine can inhibit hypoxia-stimulated metastasis via HIF-1α/VEGF/EMT which may serve as a useful additional strategy for CCA therapy.

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Citations

Nov 8, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Sunitta Saensa-ArdVeerapol Kukongviriyapan
Jan 19, 2021·Expert Opinion on Drug Delivery·Mohammad HajimolaaliFarid Dorkoosh
May 4, 2021·Digestive Diseases and Sciences·Fatma El Zahraa MohamedRajai Munir Al-Jehani

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