Chloroquine Exerts Anti-metastatic Activities Under Hypoxic Conditions in Cholangiocarcinoma Cells

Thongchot, Suyanee; Loilome, Watcharin; Yongvanit, Puangrat; Dokduang, Hasaya; Thanan, Raynoo; Techasen, Anchalee; Namwat, Nisana

doi:10.7314/apjcp.2015.16.5.2031

Cited by 13 publications

(6 citation statements)

References 22 publications

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“…Regarding CQ, its IC 50 for inhibition of CCA cell proliferation is comparable to those of other cancer cells (27)(28)(29)(30). CQ is known to inhibit metastatic activity of CCA-cells under hypoxic condition (31). Our results added the information that CQ also can inhibit proliferation of highly metastatic CCA-cells under normoxic condition.…”

Section: Discussionsupporting

confidence: 64%

Artesunate and chloroquine induce cytotoxic activity on cholangiocarcinoma cells via different cell death mechanisms

Guragain

Seubwai

Kobayashi

et al. 2018

Cell Mol Biol (Noisy-le-grand)

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Chemotherapy for cholangiocarcinoma (CCA) is not quite successful. In this study, we revisited the possibility of artesunate (ART) and chloroquine (CQ), the antimalarial drugs, as therapeutic agents against CCA. The possible mechanisms of these drugs to exert cytotoxicity on CCA cells were also explored.The effects of ART and CQ on proliferation and death patterns of two CCA cell lines, KKU-214 and its highly metastatic subtype KKU-214L5, were examined using water soluble tetrazolium (WST) assay and time-lapse photometry, respectively. To differentiate and verify the death patterns between necrosis and apoptosis, lactate dehydrogenase (LDH) release, and caspase 3 activity were measured. CellROX TM green reagent staining method was used to assess reactive oxygen species (ROS) production in ART-and CQ-treated cells. ART and CQ significantly inhibited proliferation of CCA cells. Both drugs kill malarial parasites via similar mechanism depending on ROS formation, however, ART induced necrotic cell death and CQ induced apoptotic cell death in CCA cells. ART induced LDH release, whereas CQ activated caspase 3, confirming induction of necrotic and apoptotic cell deaths by ART and CQ, respectively. ART treatment induced higher ROS production than CQ. ART and CQ induce CCA cells death via different death pathways. ART should be suitable for necrosis-sensitive CCA, whereas CQ is more suitable for apoptosis-sensitive CCA.

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Section: Discussionsupporting

confidence: 64%

Artesunate and chloroquine induce cytotoxic activity on cholangiocarcinoma cells via different cell death mechanisms

Guragain

Seubwai

Kobayashi

et al. 2018

Cell Mol Biol (Noisy-le-grand)

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“…CQ can inhibit hypoxia-stimulated metastasis via modulation of hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and epithelial mesenchymal transition (EMT) as shown in a cholangiocarcinoma cell line [ 105 ].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Repurposing Drugs in Oncology (ReDO)—chloroquine and hydroxychloroquine as anti-cancer agents

Verbaanderd¹,

Maes²,

Schaaf³

et al. 2017

ecancer

207

193

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Chloroquine (CQ) and hydroxychloroquine (HCQ) are well-known 4-aminoquinoline antimalarial agents. Scientific evidence also supports the use of CQ and HCQ in the treatment of cancer. Overall, preclinical studies support CQ and HCQ use in anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they are able to sensitise tumour cells to a variety of drugs, potentiating the therapeutic activity. Thus far, clinical results are mostly in favour of the repurposing of CQ. However, over 30 clinical studies are still evaluating the activity of both CQ and HCQ in different cancer types and in combination with various standard treatments. Interestingly, CQ and HCQ exert effects both on cancer cells and on the tumour microenvironment. In addition to inhibition of the autophagic flux, which is the most studied anti-cancer effect of CQ and HCQ, these drugs affect the Toll-like receptor 9, p53 and CXCR4-CXCL12 pathway in cancer cells. In the tumour stroma, CQ was shown to affect the tumour vasculature, cancer-associated fibroblasts and the immune system. The evidence reviewed in this paper indicates that both CQ and HCQ deserve further clinical investigations in several cancer types. Special attention about the drug (CQ versus HCQ), the dose and the schedule of administration should be taken in the design of new trials.

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“…Consistently, in vitro studies clearly demonstrated that hypoxia-induced signaling led CCA cells to gain a more malignant phenotype. For instance, low-oxygen culture conditions, as well as treatment with cobalt chloride (i.e., a chemical inducer of HIF-1α), promoted a substantial increase in CCA cell motility and invasiveness [190,191]. In a recent study the authors found that the hepatocyte growth factor (HGF) antagonist NK4 is effective on inhibiting CCA cell hypoxic growth and invasion both in vitro and in vivo.…”

Section: Hif-1α Signaling Pathwaymentioning

confidence: 99%

Multifaceted Aspects of Metabolic Plasticity in Human Cholangiocarcinoma: An Overview of Current Perspectives

Pastore

Lori

Gentilini

et al. 2020

Cells

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Cholangiocarcinoma (CCA) is a deadly tumor without an effective therapy. Unique metabolic and bioenergetics features are important hallmarks of tumor cells. Metabolic plasticity allows cancer cells to survive in poor nutrient environments and maximize cell growth by sustaining survival, proliferation, and metastasis. In recent years, an increasing number of studies have shown that specific signaling networks contribute to malignant tumor onset by reprogramming metabolic traits. Several evidences demonstrate that numerous metabolic mediators represent key-players of CCA progression by regulating many signaling pathways. Besides the well-known Warburg effect, several other different pathways involving carbohydrates, proteins, lipids, and nucleic acids metabolism are altered in CCA. The goal of this review is to highlight the main metabolic processes involved in the cholangio-carcinogeneis that might be considered as potential novel druggable candidates for this disease.

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Chloroquine Exerts Anti-metastatic Activities Under Hypoxic Conditions in Cholangiocarcinoma Cells

Cited by 13 publications

References 22 publications

Artesunate and chloroquine induce cytotoxic activity on cholangiocarcinoma cells via different cell death mechanisms

Artesunate and chloroquine induce cytotoxic activity on cholangiocarcinoma cells via different cell death mechanisms

Repurposing Drugs in Oncology (ReDO)—chloroquine and hydroxychloroquine as anti-cancer agents

Multifaceted Aspects of Metabolic Plasticity in Human Cholangiocarcinoma: An Overview of Current Perspectives

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