OTX008, a selective small-molecule inhibitor of galectin-1, downregulates cancer cell proliferation, invasion and tumour angiogenesis

Astorgues‐Xerri, Lucile; Riveiro, María E.; Tijeras‐Raballand, Annemilaï; Serova, Maria; Rabinovich, Gabriel A.; Bièche, Ivan; Vidaud, Michel; Gramont, Armand de; Martinet, Mathieu; Cvitkovic, Esteban; Faivre, Sandrine; Raymond, Éric

doi:10.1016/j.ejca.2014.06.015

Cited by 102 publications

(101 citation statements)

References 42 publications

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“…Treatment of HRAS cell tumor-bearing mice with GAL1 inhibitor OTX008 recapitulated the mistargeting effect of the Lo-sequestered HRAS variant, HRAS-tR. Previous studies have shown that OTX008 treatment reduced proliferation and invasion of cancer cells in culture (18), and our data support this notion specifically by inhibition of HRASdriven tumor growth in vivo. Moreover, combinatorial treatment with rapamycin and OTX008 ablated HRASdriven tumor progression, thus yielding an additive effect over either monotherapy, and supporting a potential clinically viable approach to treat HRAS-mutant cancer through previously uncharacterized means.…”

Section: Discussionsupporting

confidence: 79%

“…HRAS-tR). To address this, we utilized OTX008, a small-molecule inhibitor of GAL1 which has been demonstrated to be an anticancer agent (18,19). We assessed membrane microdomain distribution of HRAS in allograft tumors resected from mice following treatment with either OTX008 or vehicle, and found that OTX008 treatment resulted in enrichment of HRAS in L o domains, similar to HRAS-tR, as indicated by co-sedimentation with L o marker CAV1 (Figure 3a).…”

Section: Resultsmentioning

confidence: 99%

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Inhibition of Galectin-1 Sensitizes HRAS-driven Tumor Growth to Rapamycin Treatment

Michael

Wurtzel

Goldfinger

2016

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Section: Discussionsupporting

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Inhibition of Galectin-1 Sensitizes HRAS-driven Tumor Growth to Rapamycin Treatment

Michael

Wurtzel

Goldfinger

2016

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“…However, their poor selectivity confined their applications [15]. OTX008 was lately reported as a novel calixarene compound which is derived from anginex and bonded to Gal-1 on the side back face, far away from the β -galactoside binding site [16–18]. OTX008 could especially and selectively interact with Gal-1 and restrain its functions [18].…”

Section: Introductionmentioning

confidence: 99%

Suppression of Retinal Neovascularization by Inhibition of Galectin-1 in a Murine Model of Oxygen-Induced Retinopathy

Yang

Zhang

et al. 2017

Journal of Ophthalmology

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Galectin-1 (Gal-1) has been proved to be an important factor in the process of tumor angiogenesis recently. As a small molecule, OTX008 serves as a selective inhibitor of Gal-1. In this study, the role of Gal-1 and the antiangiogenic effect of OTX008 on retinal neovascularization (RNV) were investigated using a mouse model of oxygen-induced retinopathy. The outcome indicated that Gal-1 was overexpressed and closely related to retinal neovessels in OIR. After intravitreal injection of OTX008 at P12, the RNV was significantly reduced at P17, measuring by cross-sectional H&E staining and whole-mount fluorescence. Our results demonstrate the inhibitory function of OTX008 on RNV, which provides a promising strategy of treating retinal angiogenic diseases such as retinopathy of prematurity and proliferative diabetic retinopathy.

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“…POCA4C6 has been shown to self-assemble into vesicles or micelles that can encapsulate drugs and release them in a pH-dependent manner (Mo et al, 2015(Mo et al, , 2016. In addition to serving as a drug delivery platform, calixarene itself can show therapeutic activity: calixarene derivatives can inhibit cancer cell proliferation and invasion as well as tumor angiogenesis by inhibiting signaling pathways (Astorgues-Xerri et al, 2014). Using calixarene in combination with some anticancer drugs can provide greater therapeutic efficacy than using the drugs on their own.…”

Section: Introductionmentioning

confidence: 99%

Curcumin: a calixarene derivative micelle potentiates anti-breast cancer stem cells effects in xenografted, triple-negative breast cancer mouse models

Chen

Zhang

et al. 2017

Drug Delivery

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Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease with no approved targeted therapy. Curcumin has shown therapeutic potential against TNBC, but it shows low bioavailability and low efficacy when administered as a free drug. Here we describe a novel vehicle for in vivo delivery of curcumin based on the phosphorylated calixarene POCA4C6. Curcumin-loaded POCA4C6 micelles (CPM) were prepared using the thin-film method and they showed a unilamellar structure with an average particle size of 3.86 nm. The micelles showed high curcumin encapsulation efficiency and loading was based on liquid chromatography-tandem mass spectrometry. Studies with cell cultures suggest that CPM can sustainably release curcumin in a pH-dependent manner. The micelles efficiently inhibited proliferation, invasion, migration and tumor spheroid formation by BT-549 human breast cancer cells. These effects involved increased apoptosis and reduced levels of nuclear b-catenin and androgen receptor. After injection into tumor xenografts, CPM persisted in the tumor tissue and efficiently inhibited tumor growth without causing obvious systemic toxicity. CPM also significantly reduced levels of CD44 þ /CD133 þ breast cancer stem cells. Our results highlight the potential of CPM as an effective therapy against TNBC. ARTICLE HISTORY

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OTX008, a selective small-molecule inhibitor of galectin-1, downregulates cancer cell proliferation, invasion and tumour angiogenesis

Cited by 102 publications

References 42 publications

Inhibition of Galectin-1 Sensitizes HRAS-driven Tumor Growth to Rapamycin Treatment

Inhibition of Galectin-1 Sensitizes HRAS-driven Tumor Growth to Rapamycin Treatment

Suppression of Retinal Neovascularization by Inhibition of Galectin-1 in a Murine Model of Oxygen-Induced Retinopathy

Curcumin: a calixarene derivative micelle potentiates anti-breast cancer stem cells effects in xenografted, triple-negative breast cancer mouse models

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