Regulation of Hedgehog Signaling in Cancer by Natural and Dietary Compounds

Bao, Cheng; Kramata, Pavel; Lee, Hong Jin; Suh, Nanjoo

doi:10.1002/mnfr.201700621

Cited by 19 publications

(11 citation statements)

References 136 publications

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“…A significant contribution to the discovery of novel Hh inhibitors is given by natural compounds [11,17,22,31,32]. The first Hh inhibitor ever discovered has been Cyclopamine, a steroidal alkaloid isolated from plants of the Veratrum species [13,33].…”

Section: Introductionmentioning

confidence: 99%

Synergistic inhibition of the Hedgehog pathway by newly designed Smo and Gli antagonists bearing the isoflavone scaffold

Berardozzi

Bernardi

Infante

et al. 2018

European Journal of Medicinal Chemistry

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Aberrant activation of the Hedgehog (Hh) pathway is responsible for the onset and progression of several malignancies. Small molecules able to block the pathway at the upstream receptor Smoothened (Smo) or the downstream effector Gli1 have thus emerged recently as valuable anticancer agents. Here, we have designed, synthesized, and tested new Hh inhibitors taking advantage by the highly versatile and privileged isoflavone scaffold. The introduction of specific substitutions on the isoflavone's ring B allowed the identification of molecules targeting preferentially Smo or Gli1. Biological assays coupled with molecular modeling corroborated the design strategy, and provided new insights into the mechanism of action of these molecules. The combined administration of two different isoflavones behaving as Smo and Gli antagonists, respectively, in primary medulloblastoma (MB) cells highlighted the synergistic effects of these agents, thus paving the way to further and innovative strategies for the pharmacological inhibition of Hh signaling.

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Section: Introductionmentioning

confidence: 99%

Synergistic inhibition of the Hedgehog pathway by newly designed Smo and Gli antagonists bearing the isoflavone scaffold

Berardozzi

Bernardi

Infante

et al. 2018

European Journal of Medicinal Chemistry

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“…Adherens junction refers to the feature of all epithelial sheets and apical adhesive structures, regulating cancer invasion and metastasis 30. Hedgehog signaling is reported to modulate the tumor microenvironment in several cancers, associated with tumor cell growth, invasion, and metastasis 31, 32. Hence, we presumed POM121 may participate in tumorigenesis, invasion and metastasis.…”

Section: Discussionmentioning

confidence: 96%

POM121 is identified as a novel prognostic marker of oral squamous cell carcinoma

Ma¹,

Li²,

Jia³

et al. 2019

J. Cancer

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Background: The aim of this study was to confirm the role of nuclear pore membrane protein 121(POM121) in oral squamous cell carcinoma and to explore the underlying mechanism.Methods: POM121mRNA and protein expressions were evaluated in OSCC tissues and normal oral tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. The relationship between POM121 expression and clinical characteristics was analyzed. Bioinformatics analysis was performed to explore the possible mechanisms how POM121 affected OSCC.Results: We confirmed that POM121 mRNA expression in OSCC tissues was significantly higher than that in non-tumorous tissues, as was POM121 protein expression. POM121 expression was associated with distant metastasis and TNM stage. Multivariate analysis confirmed POM121 expression as an independent prognostic factor for OSCC patients. OSCC patients with high POM121 expression had a worse overall survival (OS) compared with patients with low POM121 expression. Bioinformatics analysis indicated POM121 may regulate OSCC through hedgehog and /or p53 signaling pathway.Conclusion: Targeting of POM121 expression levels could provide new diagnostic and therapeutic strategies for OSCC patients.

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“…Moreover, involvement of Hedgehog (Hh) signaling in CSC has been suggested in studies of multiple human cancers [ 15 ]. Hh signaling is activated in Bcr-Abl-positive leukemia stem cells (LSC), and pharmacological inhibitors of Smo reduced leukemia stem cells in vivo [ 16 ], suggesting that Smo inhibition could be an effective treatment strategy in reducing tumor relapse and drug resistance in chronic myeloid leukemia. Dysregulation of these pathways is hypothesized to promote gradual CSC differentiation, leading to decreased tumor viability in response to chemotherapeutics, and making them an attractive target for the treatment of both bulk tumors and CSCs [ 17 ].…”

Section: Hallmarks Of Cscmentioning

confidence: 99%

Natural Products Targeting Cancer Stem Cells for Augmenting Cancer Therapeutics

Meerson

Khatib

Mahajna

2021

IJMS

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Cancer stem cells (CSC) have been identified in several types of solid tumors. In some cases, CSC may be the source of all the tumor cells, the cause of the tumor’s resistance to chemotherapeutic agents, and the source of metastatic cells. Thus, a combination therapy targeting non-CSC tumor cells as well as specifically targeting CSCs holds the potential to be highly effective. Natural products (NPs) have been a historically rich source of biologically active compounds and are known for their ability to influence multiple signaling pathways simultaneously with negligible side effects. In this review, we discuss the potential of NPs in targeting multiple signaling pathways in CSC and their potential to augment the efficacy of standard cancer therapy. Specifically, we focus on the anti-CSC activities of flavonoids, FDA-approved drugs originating from natural sources. Additionally, we emphasize the potential of NPs in targeting microRNA-mediated signaling, given the roles of microRNA in the maintenance of the CSC phenotype.

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Regulation of Hedgehog Signaling in Cancer by Natural and Dietary Compounds

Cited by 19 publications

References 136 publications

Synergistic inhibition of the Hedgehog pathway by newly designed Smo and Gli antagonists bearing the isoflavone scaffold

Synergistic inhibition of the Hedgehog pathway by newly designed Smo and Gli antagonists bearing the isoflavone scaffold

POM121 is identified as a novel prognostic marker of oral squamous cell carcinoma

Natural Products Targeting Cancer Stem Cells for Augmenting Cancer Therapeutics

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