Inhibition of malignant thyroid carcinoma cell proliferation by Ras and galectin-3 inhibitors

Menachem, Assaf; Bodner, O; Pastor, Joaquin; Raz, Avraham; Kloog, Yoel

doi:10.1038/cddiscovery.2015.47

Cited by 22 publications

(21 citation statements)

References 46 publications

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“…One of them is Galectin-3 (Gal-3), an endogenous lectin molecule and a member of the galectin family, that have a recognition domain for β-galactoside 24 . Gal-3 is ubiquitously expressed on the surface of tumor and metastatic cancer cells, and is involved in multiple processes such as cell to cell, and cell to matrix adhesion as well as tumor growth, and metastasis both in vitro , and in vivo 25 , 26 . Since Gal-3 plays an important role in the growth, survival, and spread of cancer cells, it has been proposed as an analytical biomarker of cancer 27 .…”

Section: Introductionmentioning

confidence: 99%

Oxidative DNA damage induced by ROS-modulating agents with the ability to target DNA: A comparison of the biological characteristics of citrus pectin and apple pectin

Salehi

Behboudi

Kavoosi

2018

Sci Rep

147

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DNA targeting anticancer agents have been very successful in clinic, especially, when used in combinatorial therapy. But unfortunately, they often exhibit high levels of toxicity towards normal cells. Hence, much effort has been put into finding agents with more selectivity, and less toxicity. Pectins are natural polysaccharides, and beneficial nutritional fibers that have attracted attentions due to their antitumor properties. However, their molecular targets, and mechanism of action are widely unknown. Here, we have reported that citrus pectin (CP) and apple pectin (AP) selectively suppress viability in MDA-MB-231, MCF-7 and T47D human Breast cancer cells, while non-toxic to L929 normal cells. Upon CP, and AP treatments, cancer cells’ ROS content increased rapidly, and led to the collapse of the mitochondrial transmembrane potential which functions upstream of the caspase-dependent apoptosis. CP and AP treated cancer cells were also arrested at the S and G1 or G2/M phases of the cell cycle, respectively. Furthermore, mRNA expression of Galectin-3 (a multi-functional lectin involved in cell adhesion, cell cycle, and apoptosis) reduced in both CP and AP treated cells. Growth inhibition of MDA-MB-231 cells by CP, and AP was concomitant with DNA damage (oxidation, and strand breaks). In this context, in an effort to clarify the mechanism of action, we showed that CP, and AP are able to interact with DNA. The strength and mode of DNA binding were established by spectroscopy techniques. We demonstrated that CP, and AP bind to dsDNA by intercalation, and groove binding/partial intercalation, respectively. In conclusion, our findings suggest that CP, and AP induce apoptosis in MDA-MB-231 cells by increasing the release of ROS, which may be related to the mitochondrial apoptosis pathway, and direct interactions with DNA. Our data indicate that these compounds may be potentially useful in cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Oxidative DNA damage induced by ROS-modulating agents with the ability to target DNA: A comparison of the biological characteristics of citrus pectin and apple pectin

Salehi

Behboudi

Kavoosi

2018

Sci Rep

147

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“…Tumor growth in vivo was also strongly diminished. These innovative findings could be clinically relevant and should lead to the development of new approaches for treating ATC patients [69].…”

Section: Combination To Mapk/mek Inhibitorsmentioning

confidence: 96%

“…Furthermore, the β-galactoside-binding protein, plays a crucial role in diagnosing biomarkers and is also an activator of important signaling cascades [69,70]. Galectin-3 can bind RAS proteins with a preference for KRAS.…”

Section: Combination To Mapk/mek Inhibitorsmentioning

confidence: 99%

“…Used as a single agent, this study did not demonstrate any pieces of evidence of improvement of patient overall survival. Moreover, patients often acquired resistance after 1 or 2 years of sorafenib administration [69]. Finally, toxic side effects such as hand-foot syndrome, diarrhea, fatigue, rash, and weight loss affected approximately 80% of sorafenib-treated patients, rendering this molecule not useable alone for cancer treatment.…”

Section: Combination With Targeted Therapiesmentioning

confidence: 99%

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Combinatorial Therapies in Thyroid Cancer: An Overview of Preclinical and Clinical Progresses

Gheysen

Saussez

Journé

2020

Cells

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Accounting for about 2% of cancers diagnosed worldwide, thyroid cancer has caused about 41,000 deaths in 2018. Despite significant progresses made in recent decades in the treatment of thyroid cancer, many resistances to current monotherapies are observed. In our complete review, we report all treatments that were tested in combination against thyroid cancer. Many preclinical studies investigating the effects of inhibitors of the MAPK and PI3K pathways highlighted the importance of mutations in such signaling pathways and their impacts on the subsequent efficacy of targeted therapies, thus reinforcing the need of more personalized therapeutic strategies. Our review also points out the multiple possibilities of combinatory strategies, particularly using therapies targeting proliferation, survival, angiogenesis, and in combination with conventional treatments such as chemotherapies. In any case, resistances to anticancer therapies always develop through the activation of alternative signaling pathways. Combinatory treatments aim to blockade such mechanisms, which are gradually decrypted, thus offering new perspectives for the future. The preclinical and clinical aspects of our review allow us to have a global opinion of the different therapeutic options currently evaluated in combination and to be aware about new perspectives of treatment of thyroid cancer.

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“…The antitumor effects of MCP were associated with an antiangiogenic activity, since MCP also inhibited capillary tube formation in vitro in human endothelial cells. Recently, Menachem et al studied in vivo the combined inhibition of Ras and Gal-3 with FTS ( S - trans farnesylthiosalicylic acid, Salirasib) and MCP, respectively, for the treatment of aggressive anaplastic thyroid carcinoma ( 143 ). Interestingly, FTS and MCP inhibited tumor growth in nude mice showing decreased levels of Gal-3, K-Ras-GTP, and p-ERK.…”

Section: Structure Function and Clinical Prospects Of Lectin-inhibimentioning

confidence: 99%

Turning-Off Signaling by Siglecs, Selectins, and Galectins: Chemical Inhibition of Glycan-Dependent Interactions in Cancer

et al. 2016

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Aberrant glycosylation, a common feature associated with malignancy, has been implicated in important events during cancer progression. Our understanding of the role of glycans in cancer has grown exponentially in the last few years, concurrent with important advances in glycomics and glycoproteomic technologies, paving the way for the validation of a number of glycan structures as potential glycobiomarkers. However, the molecular bases underlying cancer-associated glycan modifications are still far from understood. Glycans exhibit a natural heterogeneity, crucial for their diverse functional roles as specific carriers of biologically relevant information. This information is decoded by families of proteins named lectins, including sialic acid-binding immunoglobulin (Ig)-like lectins (siglecs), C-type lectin receptors (CLRs), and galectins. Siglecs are primarily expressed on the surface of immune cells and differentially control innate and adaptive immune responses. Among CLRs, selectins are a family of cell adhesion molecules that mediate interactions between cancer cells and platelets, leukocytes, and endothelial cells, thus facilitating tumor cell invasion and metastasis. Galectins, a family of soluble proteins that bind β-galactoside-containing glycans, have been implicated in diverse events associated with cancer biology such as apoptosis, homotypic cell aggregation, angiogenesis, cell migration, and tumor-immune escape. Consequently, individual members of these lectin families have become promising targets for the design of novel anticancer therapies. During the past decade, a number of inhibitors of lectin–glycan interactions have been developed including small-molecule inhibitors, multivalent saccharide ligands, and more recently peptides and peptidomimetics have offered alternatives for tackling tumor progression. In this article, we review the current status of the discovery and development of chemical lectin inhibitors and discuss novel strategies to limit cancer progression by targeting lectin–glycan interactions.

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Inhibition of malignant thyroid carcinoma cell proliferation by Ras and galectin-3 inhibitors

Cited by 22 publications

References 46 publications

Oxidative DNA damage induced by ROS-modulating agents with the ability to target DNA: A comparison of the biological characteristics of citrus pectin and apple pectin

Oxidative DNA damage induced by ROS-modulating agents with the ability to target DNA: A comparison of the biological characteristics of citrus pectin and apple pectin

Combinatorial Therapies in Thyroid Cancer: An Overview of Preclinical and Clinical Progresses

Turning-Off Signaling by Siglecs, Selectins, and Galectins: Chemical Inhibition of Glycan-Dependent Interactions in Cancer

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