Chloroquine-based hybrid molecules as promising novel chemotherapeutic agents

Srivastava, Vandana; Lee, Hoyun

doi:10.1016/j.ejphar.2015.04.048

Cited by 29 publications

(19 citation statements)

References 94 publications

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“…CQ was developed from natural product quinine eighty years ago and is still widely used for the control of malaria worldwide. Besides its antimalarial properties, a broader spectrum of CQ pharmacological activities, including anti-inflammatory and anticancer activity has been discovered and explored over the years [16, 17]. CQ, and its derivatives like hydroxychloroquine (HCQ), have also been recognized as effective autophagy inhibitors that exhibit beneficial anticancer properties [18, 19].…”

Section: Introductionmentioning

confidence: 99%

Polymeric chloroquine as an inhibitor of cancer cell migration and experimental lung metastasis

Xie

et al. 2016

Journal of Controlled Release

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Chloroquine (CQ) is a widely used antimalarial drug with emerging potential in anticancer therapies due to its apparent inhibitory effects on CXCR4 chemokine receptor, autophagy, and cholesterol metabolism. This study reports on polymeric CQ (pCQ) as a macromolecular drug with antimetastatic activity. The pCQ polymers were synthesized by copolymerization of methacryloylated hydroxy-CQ (HCQ) and N-(2-hydroxypropyl)methacrylamide (HPMA). The results show that pCQ is significantly more effective in inhibiting cancer cell migration and invasion when compared with the parent HCQ. The proposed mechanism of action at least partially relies on the ability of pCQ to inhibit cell migration mediated by the CXCR4/CXCL12 pathway. The pCQ also demonstrates superior inhibitory activity over HCQ when tested in a mouse model of experimental lung metastasis. Lastly, pCQ shows the ability to efficiently translocate to the cytoplasm while exhibiting lower cytotoxicity than HCQ. Overall, this study supports pCQ as a promising polymeric drug platform suitable for use in combination antimetastatic strategies and potential use in cytoplasmic drug delivery.

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Section: Introductionmentioning

confidence: 99%

Polymeric chloroquine as an inhibitor of cancer cell migration and experimental lung metastasis

Xie

et al. 2016

Journal of Controlled Release

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“…The present study showed that mRNA and protein expression levels of S100A3 were significantly increased in HCC and that S100A3 expression in human HCC was significantly inhibited by sodium cantharidinate. Effective anti-cancer agents exhibit the desirable feature of potent cytotoxicity towards tumor cells while eliciting limited adverse effects on normal cells (40). Sodium cantharidinate may directly destroy the liver cancer cell lines, which provided the favorable theoretical basis for the application of treatment of primary liver cancer (41).…”

Section: Discussionmentioning

confidence: 99%

Role of S100A3 in human hepatocellular carcinoma and the anticancer effect of sodium cantharidinate

Tao

Wang

Qiu

et al. 2017

Experimental and Therapeutic Medicine

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The fifth most common cancer worldwide is hepatocellular carcinoma (HCC), which has an annual mortality rate of ~800,000. Although surgical procedures for HCC, such as hepatic resection and liver transplantation, have progressed and the outcomes of patients have improved, HCC is still characterized by frequent recurrence, even after liver transplantation. In the present study the expression of the protein coding gene, S100 calcium binding protein A3 (S100A3), was observed in 62 HCC tissues and tumor-surrounding tissues. The present study indicated that S100A3 activation was involved in tumorigenesis and tumor aggressiveness. The protein and mRNA expression levels of S100A3 in the human HCC cell line (HepG2) were investigated using western blotting and reverse transcription-quantitative polymerase chain reaction analysis, respectively. The function of sodium cantharidinate in inducing HCC cell apoptosis was also investigated. Sodium cantharidinate inhibited the protein and gene expression of S100A3 in HepG2 cells in vitro. These data suggested that S100A3 has an important role in human HCC. The present study indicates that the functional properties of sodium cantharidinate are promising for the development of a novel drug that may control the expression of S100A3 and improve the treatment of human HCC in the near future.

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“…282 In normal and tumor tissue alike, the activity of STAT3 itself affects vascularity and pericyte interactions with their microenvironment, including myeloid cells. 20,289,290 What is the technical maturity of the concepts of CQ use against tumors? 147,287,288 Therefore, the activation of STAT3 by constitutive DNA damage in cancer cells could facilitate selective drug effects on the tumor nest through the circulation, while having discrete indirect effects on the local tissue microenvironment owing to the secretome of the tumor.…”

Section: Feasibility Of Treating Malignant Tumors With Cq: Strengths mentioning

confidence: 99%

“…To some extent, cellular targeting by CQs can be achieved by conjugation with specific moieties, including sugar groups, and by the generation of hybrid molecules, such as CQ-artemisinin. 20,289,290 What is the technical maturity of the concepts of CQ use against tumors? Even though CQ is an established drug against certain conditions, its use in cancer is still in its infancy, as is evident by the clinical trials that have been publicized.…”

Section: Feasibility Of Treating Malignant Tumors With Cq: Strengths mentioning

confidence: 99%

Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

2019

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Chloroquines are 4-aminoquinoline-based drugs mainly used to treat malaria. At pharmacological concentrations, they have significant effects on tissue homeostasis, targeting diverse signaling pathways in mammalian cells. A key target pathway is autophagy, which regulates macromolecule turnover in the cell. In addition to affecting cellular metabolism and bioenergetic flow equilibrium, autophagy plays a pivotal role at the interface between inflammation and cancer progression. Chloroquines consequently have critical effects in tissue metabolic activity and importantly, in key functions of the immune system. In this article, we will review the work addressing the role of chloroquines in the homeostasis of mammalian tissue, and the potential strengths and weaknesses concerning their use in cancer therapy.

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Chloroquine-based hybrid molecules as promising novel chemotherapeutic agents

Cited by 29 publications

References 94 publications

Polymeric chloroquine as an inhibitor of cancer cell migration and experimental lung metastasis

Polymeric chloroquine as an inhibitor of cancer cell migration and experimental lung metastasis

Role of S100A3 in human hepatocellular carcinoma and the anticancer effect of sodium cantharidinate

Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

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