Chloroquine and its analogs: A new promise of an old drug for effective and safe cancer therapies

Solomon, V. Raja; Lee, Hoyun

doi:10.1016/j.ejphar.2009.06.063

Cited by 460 publications

(373 citation statements)

References 150 publications

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“…Chloroquine, a commonly used autophagy inhibitor, has been used as a sensitizer in cancer therapies. 43 However, a controversy exists in terms of chloroquine efficacy. 44 One explanation is that normal cells also use autophagy to maintain homeostasis, and inhibition of autophagy by chloroquine would also sensitize healthy organs such as kidneys to chemotherapy resulting in severe side effects.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of ATG14 by EGR1-MIR152 sensitizes ovarian cancer cells to cisplatin-induced apoptosis by inhibiting cyto-protective autophagy

et al. 2015

Autophagy

146

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Cisplatin is commonly used in ovarian cancer treatment by inducing apoptosis in cancer cells as a result of lethal DNA damage. However, the intrinsic and acquired resistance to cisplatin in cancer cells remains a big challenge for improving overall survival. The cyto-protective functions of autophagy in cancer cells have been suggested as a potential mechanism for chemoresistance. Here, we reported MIR152 as a new autophagy-regulating miRNA that plays a role in cisplatin-resistance. We showed that MIR152 expression was dramatically downregulated in the cisplatinresistant cell lines A2780/CP70, SKOV3/DDP compared with their respective parental cells, and in ovarian cancer tissues associated with cisplatin-resistance. Overexpression of MIR152 sensitized cisplatin-resistant ovarian cancer cells by reducing cisplatin-induced autophagy, enhancing cisplatin-induced apoptosis and inhibition of cell proliferation. A mouse subcutaneous xenograft tumor model using A2780/CP70 cells with overexpressing MIR152 was established and displayed decreased tumor growth in response to cisplatin. We also identified that ATG14 is a functional target of MIR152 in regulating autophagy inhibition. Furthermore, we found that EGR1 (early growth response 1) regulated the MIR152 gene at the transcriptional level. Ectopic expression of EGR1 enhanced efficacy of chemotherapy in A2780/CP70 cells. More importantly, these findings were relevant to clinical cases. Both EGR1 and MIR152 expression levels were significantly lower in ovarian cancer tissues with high levels of ERCC1 (excision repair cross-complementation group 1), a marker for cisplatin-resistance. Collectively, these data provide insights into novel mechanisms for acquired cisplatinresistance. Activation of EGR1 and MIR152 may be a useful therapeutic strategy to overcome cisplatin-resistance by preventing cyto-protective autophagy in ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Downregulation of ATG14 by EGR1-MIR152 sensitizes ovarian cancer cells to cisplatin-induced apoptosis by inhibiting cyto-protective autophagy

et al. 2015

Autophagy

146

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“…6 For instance, chloroquine (CQ), 1 in Figure 1, which is known to inhibit proliferation of breast cancer cells, 7 can cause defects in DNA synthesis and repair, and also induce cell apoptosis and necrosis. 2,8 In the case of cinnamic acid, it has been reported that one of its modes of action seems to be inhibition of protein isoprenylation, which blocks mitogenic signal transduction. 4 Still, cinnamic acid analogues have also shown to be antiangiogenic, antileukemic as well as inhibitors of transglutaminase, aminopeptidase N, DNA synthesis, and of a specific tyrosine kinase.…”

mentioning

confidence: 99%

Recycling antimalarial leads for cancer: Antiproliferative properties of N-cinnamoyl chloroquine analogues

Pérez

Fernandes

Mateus

et al. 2013

Bioorganic & Medicinal Chemistry Letters

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a b s t r a c tCinnamic acids and quinolines are known as useful scaffolds in the discovery of antitumor agents. Therefore, N-cinnamoylated analogues of chloroquine, recently reported as potent dual-action antimalarials, were evaluated against three different cancer cell lines: MKN-28, Caco-2, and MCF-7. All compounds display anti-proliferative activity in the micromolar range against the three cell lines tested, and most of them were more active than their parent drug, chloroquine, against all cell lines tested. Hence, N-cinnamoyl-chloroquine analogues are a good start towards development of affordable antitumor leads.Ó 2013 Elsevier Ltd. All rights reserved.Cancer remains a life threatening disease worldwide despite of available conventional treatments such as surgery, radiotherapy and/or chemotherapy. The still considerable limitations of cancer chemotherapy are mainly associated with low efficacy, high toxicity, and emergence of drug resistance, and not less important their high cost.1 Hence, there is a wide range of scientific approaches to find better chemotherapeutic agents, including those based on recycling or repositioning of well-known drugs used to treat diseases other than cancer. 2 In this connection, both quinolines and cinnamic acids, which are found in different natural resources and widely used for diverse medicinal purposes, 3,4 have demonstrated to constitute scaffolds of great interest for the development of new antitumor agents. 5,6 In one hand, quinoline synthetic versatility promotes the development of large diversity of quinoline analogues. On the other, the 3-phenyl acrylic acid moiety offers three main reactive sites: substitutions at the phenyl ring, additions at the a,b-unsaturated carbonyl moiety, and the carboxylic acid functionality reactions.

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“…This has attracted the use of autophagy inhibitors to enhance the efficacy of chemotherapy. Chloroquine, an autophagy inhibitor, has been reported to sensitise a variety of cancers to conventional chemotherapy in vitro and in vivo Solomon and Lee, 2009), and enhance survival of patients with glioblastoma multiforme when used as an adjuvant with conventional chemotherapy or radiotherapy (Briceno et al, 2007).…”

Section: Chloroquinementioning

confidence: 99%

New frontiers in promoting tumour cell death: targeting apoptosis, necroptosis and autophagy

2012

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Chloroquine and its analogs: A new promise of an old drug for effective and safe cancer therapies

Cited by 460 publications

References 150 publications

Downregulation of ATG14 by EGR1-MIR152 sensitizes ovarian cancer cells to cisplatin-induced apoptosis by inhibiting cyto-protective autophagy

Downregulation of ATG14 by EGR1-MIR152 sensitizes ovarian cancer cells to cisplatin-induced apoptosis by inhibiting cyto-protective autophagy

Recycling antimalarial leads for cancer: Antiproliferative properties of N-cinnamoyl chloroquine analogues

New frontiers in promoting tumour cell death: targeting apoptosis, necroptosis and autophagy

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