Natural Products Inspired Modulators of Cancer Stem Cells-specific Signaling Pathways Notch and Hedgehog

2019 ◽  
Vol 24 (36) ◽  
pp. 4251-4269 ◽  
Author(s):  
Rocco Palermo ◽  
Francesca Ghirga ◽  
Maria Grazia Piccioni ◽  
Flavia Bernardi ◽  
Nadezda Zhdanovskaya ◽  
...  
Keyword(s):  
Stem Cells ◽  
Natural Products ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Anticancer Agents ◽  
Chemical Biology ◽  
Total Syntheses ◽  
Lead Compounds ◽  
Promising Strategy ◽  
Anticancer Drug Discovery

It is nowadays widely accepted that some tumors have a niche of cells endowed with stemness features, which may cause resistance to conventional anticancer therapies and relapse/recurrence of the malignancy. These cells are usually referred to as cancer stem cells (CSCs) and, different from normal cancer cells, are rather quiescent. Targeting CSCs is thus a highly challenging but promising strategy to counteract tumor growth, and to develop innovative anticancer agents. Here, we review the chemical, biological and multidisciplinary efforts that have been spent in targeting CSCsspecific signaling pathways Notch and Hedgehog (Hh) for anticancer drug discovery. In particular, the use of natural products as a valuable source of lead compounds or chemical biology tools is emphasized. Examples of natural products functionalization through semi-synthetic transformations or total syntheses, aimed at improving pharmacokinetics and/or pharmacodynamics properties of natural products in Notch or Hh inhibition, are provided as well.

scholarly journals Natural Products Targeting Cancer Stem Cells for Augmenting Cancer Therapeutics

2021 ◽  
Vol 22 (23) ◽  
pp. 13044
Author(s):  
Ari Meerson ◽  
Soliman Khatib ◽  
Jamal Mahajna
Keyword(s):  
Stem Cells ◽  
Natural Products ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Cancer Therapeutics ◽  
Chemotherapeutic Agents ◽  
Biologically Active ◽  
Approved Drugs ◽  
Multiple Signaling

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.

Natural products targeting cancer stem cells: a revisit

2021 ◽  
Vol 28 ◽  
Author(s):  
Jiahua Cui ◽  
Jiajun Qian ◽  
Larry Ming-Cheung Chow ◽  
Jinping Jia
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Natural Products ◽  
Cancer Stem Cells ◽  
Therapeutic Potential ◽  
Tumor Development ◽  
Biologically Active ◽  
Cellular Targets ◽  
Drug Candidates ◽  
Enhanced Expression

Background: The proposed central role of cancer stem cells (CSCs) in tumor development has been extended to explain the diverse oncologic phenomena such as multidrug resistance, metastasis and tumor recurrence in clinics. Due to the enhanced expression of ATP-binding cassette transporters and anti-apoptotic factors, stagnation on G0 phase and the strong ability of self-renewal, the CSCs were highly resistant to clinical anticancer drugs. Therefore, the discovery of new drug candidates that could effectively eradicate cancer stem cells afforded promising outcomes in cancer therapy. Introduction: Natural products and their synthetic analogues are a rich source of biologically active compounds and several of them have already been recognized as potent CSCs killers. We aim to provide a collection of recently identified natural products that suppressed the survival of the small invasive CSC populations and combated the drug resistance of these cells in chemotherapy. Results and Conclusion: These anti-CSCs natural products included flavonoids, stilbenes, quinones, terpenoids, polyketide antibiotics, steroids and alkaloids. In the present review, we highlighted the therapeutic potential of natural products and their derivatives against the proliferation and drug resistance of CSCs, their working mechanisms and related structure-activity relationships. Meanwhile, in this survey, several natural products with diverse cellular targets such as the naphthoquinone shikonin and the stilbene resveratrol were characterized as promising lead compounds for future development.

Deciphering the signaling pathways of cancer stem cells of glioblastoma multiforme: Role of Akt/mTOR and MAPK pathways

2011 ◽  
Vol 51 (1) ◽  
pp. 164-170 ◽  
Author(s):  
Meena Jhanwar-Uniyal ◽  
Ladislau Albert ◽  
Elise McKenna ◽  
Michael Karsy ◽  
Priya Rajdev ◽  
...  
Keyword(s):  
Stem Cells ◽  
Glioblastoma Multiforme ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Mapk Pathways

scholarly journals Shared signaling pathways in normal and breast cancer stem cells

2011 ◽  
Vol 10 (1) ◽  
pp. 38 ◽  
Author(s):  
Vimla Band ◽  
Xiangshan Zhao ◽  
GautamK Malhotra ◽  
Hamid Band
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Breast Cancer Stem Cells

scholarly journals Hepatic Cancer Stem Cells: Molecular Mechanisms, Therapeutic Implications, and Circulating Biomarkers

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4550
Author(s):  
Laura Gramantieri ◽  
Catia Giovannini ◽  
Fabrizia Suzzi ◽  
Ilaria Leoni ◽  
Francesca Fornari
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Anticancer Agents ◽  
Tumor Heterogeneity ◽  
Molecular Mechanisms ◽  
Driving Forces ◽  
Predictive Biomarkers ◽  
Molecular Classification ◽  
Circulating Biomarkers ◽  
Therapeutic Implications

Hepatocellular carcinoma (HCC) is one of the deadliest cancers. HCC is associated with multiple risk factors and is characterized by a marked tumor heterogeneity that makes its molecular classification difficult to apply in the clinics. The lack of circulating biomarkers for the diagnosis, prognosis, and prediction of response to treatments further undermines the possibility of developing personalized therapies. Accumulating evidence affirms the involvement of cancer stem cells (CSCs) in tumor heterogeneity, recurrence, and drug resistance. Owing to the contribution of CSCs to treatment failure, there is an urgent need to develop novel therapeutic strategies targeting, not only the tumor bulk, but also the CSC subpopulation. Clarification of the molecular mechanisms influencing CSC properties, and the identification of their functional roles in tumor progression, may facilitate the discovery of novel CSC-based therapeutic targets to be used alone, or in combination with current anticancer agents, for the treatment of HCC. Here, we review the driving forces behind the regulation of liver CSCs and their therapeutic implications. Additionally, we provide data on their possible exploitation as prognostic and predictive biomarkers in patients with HCC.

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