Natural Products as a Promising Therapeutic Strategy to Target Cancer Stem Cells

2021 ◽  
Vol 28 ◽  
Author(s):  
Merve Erkisa ◽  
Melda Sariman ◽  
Oyku Gonul Geyik ◽  
Caner Geyik Geyik ◽  
Tatjana Stanojkovic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Natural Products ◽  
Cancer Stem Cells ◽  
Immune Surveillance ◽  
Research Area ◽  
Chemical Library ◽  
New Research ◽  
The Cost ◽  
Near Future ◽  
Potential Use

: Cancer is still a deadly disease, and its treatment desperately needs to be managed in a very sophisticated way through fast-developing novel strategies. Most of the cancer cases eventually develop into recurrencies, for which cancer stem cells (CSCs) are thought to be responsible. They are considered as a subpopulation of all cancer cells of tumor tissue with aberrant regulation of self-renewal, unbalanced proliferation, and cell death properties. Moreover, CSCs show a serious degree of resistance to chemotherapy or radiotherapy and immune surveillance as well. Therefore, new classes of drugs are rushing into the market each year, which makes the cost of therapy increase dramatically. Natural products are also becoming a new research area as a diverse chemical library to suppress CSCs. Some of the products even show promise in this regard. So, the near future could witness the introduction of natural products as a source of new chemotherapy modalities, which may result in the development of novel anticancer drugs. They could also be a reasonably-priced alternative to highly expensive current treatments. Nowadays, considering the effects of natural compounds on targeting surface markers, signaling pathways, apoptosis, and escape from immunosurveillance have been a highly intriguing area in preclinical and clinical research. In this review, we present scientific advances regarding their potential use in the inhibition of CSCs and the mechanisms by which they kill the CSCs.

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.

scholarly journals Mitotic quiescence in hepatic cancer stem cells: An incognito mode

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Kandasamy Ashokachakkaravarthy ◽  
Biju Pottakkat
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Immune Evasion ◽  
Immune Surveillance ◽  
Cancer Recurrence ◽  
Tumor Formation ◽  
Proliferating Cells ◽  
Recurrence Rates

Hepatocellular carcinoma represents one of the most aggressive cancers with high recurrence rates. The high recurrence is a major problem in the management of this disease. Cancer stem cells (CSCs) are often regarded as the basis of cancer recurrence. The anti-proliferative therapy kills the proliferating cells but induces mitotic quiescence in CSCs which remain as residual dormant CSCs. Later on, withdrawal of treatment reactivates the residual CSCs from dormancy to produce new cancer cells. The proliferation of these newly formed cancer cells initiates new tumor formation in the liver leading to tumor recurrence. HCC cells evade the immune surveillance via modulating the key immune cells by alpha feto-protein (AFP) secreted from CSCs or hepatic progenitor cells. This AFP mediated immune evasion assists in establishing new tumors by cancer cells in the liver. In this review, we will summarise the CSC mechanisms of recurrence, mitotic quiescence, dormancy and reactivation of CSCs, metastasis and immune evasion of hepatocellular carcinoma.

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.

scholarly journals Cancer Stem Cells: Emerging Key Players in Immune Evasion of Cancers

2021 ◽  
Vol 9 ◽  
Author(s):  
Martina Mang Leng Lei ◽  
Terence Kin Wah Lee
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Immune Cells ◽  
Immune Surveillance ◽  
Suppressor Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Treg Cells ◽  
Undifferentiated Cancer

Cancer stem cells (CSCs) are subpopulations of undifferentiated cancer cells within the tumor bulk that are responsible for tumor initiation, recurrence and therapeutic resistance. The enhanced ability of CSCs to give rise to new tumors suggests potential roles of these cells in the evasion of immune surveillance. A growing body of evidence has described the interplay between CSCs and immune cells within the tumor microenvironment (TME). Recent data have shown the pivotal role of some major immune cells in driving the expansion of CSCs, which concurrently elicit evasion of the detection and destruction of various immune cells through a number of distinct mechanisms. Here, we will discuss the role of immune cells in driving the stemness of cancer cells and provide evidence of how CSCs evade immune surveillance by exerting their effects on tumor-associated macrophages (TAMs), dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), T-regulatory (Treg) cells, natural killer (NK) cells, and tumor-infiltrating lymphocytes (TILs). The knowledge gained from the interaction between CSCs and various immune cells will provide insight into the mechanisms by which tumors evade immune surveillance. In conclusion, CSC-targeted immunotherapy emerges as a novel immunotherapy strategy against cancer by disrupting the interaction between immune cells and CSCs in the TME.

scholarly journals Targeting Cancer Stem Cells—A Renewed Therapeutic Paradigm

2017 ◽  
Vol 13 (01) ◽  
pp. 45
Author(s):  
Catherine L Amey ◽  
Antoine E Karnoub ◽  
◽  
Keyword(s):  
Stem Cells ◽  
Cancer Therapy ◽  
Cancer Stem Cells ◽  
Residual Disease ◽  
Immune Surveillance ◽  
Tumor Initiating Cells ◽  
Primary Tumors ◽  
Cancer Management ◽  
After Cancer ◽  
A Minor

Metastasis is often accompanied by radio- and chemotherapeutic resistance to anticancer treatments and is the major cause of death in cancer patients. Better understanding of how cancer cells circumvent therapeutic insults and how disseminated cancer clones generate life-threatening metastases would therefore be paramount to the development of effective therapeutic approaches for clinical management of malignant disease. Mounting reports over the past two decades have provided evidence for the existence of a minor population of highly malignant cells within liquid and solid tumors, which are capable of self-renewing and of regenerating secondary growths with the heterogeneity of the primary tumors from which they derive. These cells, called tumor-initiating cells or cancer stem cells (CSCs) exhibit increased resistance to standard radio- and chemotherapies and appear to have mechanisms that enable them to evade immune surveillance. CSCs are therefore considered to be responsible for systemic residual disease after cancer therapy, as well as for disease relapse. How CSCs develop, the nature of the interactions they establish with their microenvironment, their phenotypic and functional characteristics, as well as their molecular dependencies have all taken center stage in cancer therapy. Indeed, improved understanding of CSC biology is critical to the development of important CSC-based anti-neoplastic approaches that have the potential to radically improve cancer management. Here, we summarize some of the most pertinent elements regarding CSC development and properties, and highlight some of the clinical modalities in current development as anti-CSC therapeutics.

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 Induction of Lysosome Membrane Permeabilization as a Therapeutic Strategy to Target Pancreatic Cancer Stem Cells

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1790 ◽  
Author(s):  
Timothy P. Cash ◽  
Sonia Alcalá ◽  
María del Rosario Rico-Ferreira ◽  
Elena Hernández-Encinas ◽  
Jennifer García ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Therapeutic Strategy ◽  
Membrane Permeabilization ◽  
Ductal Adenocarcinoma ◽  
Chemical Library ◽  
Specific Chemical ◽  
Pancreatic Cancer Stem Cells

Despite significant efforts to improve pancreatic ductal adenocarcinoma (PDAC) clinical outcomes, overall survival remains dismal. The poor response to current therapies is partly due to the existence of pancreatic cancer stem cells (PaCSCs), which are efficient drivers of PDAC tumorigenesis, metastasis and relapse. To find new therapeutic agents that could efficiently kill PaCSCs, we screened a chemical library of 680 compounds for candidate small molecules with anti-CSC activity, and identified two compounds of a specific chemical series with potent activity in vitro and in vivo against patient-derived xenograft (PDX) cultures. The anti-CSC mechanism of action of this specific chemical series was found to rely on induction of lysosomal membrane permeabilization (LMP), which is likely associated with the increased lysosomal mass observed in PaCSCs. Using the well characterized LMP-inducer siramesine as a tool molecule, we show elimination of the PaCSC population in mice implanted with tumors from two PDX models. Collectively, our approach identified lysosomal disruption as a promising anti-CSC therapeutic strategy for PDAC.

Targeting Cancer Stem Cells with Natural Products

2012 ◽  
Vol 13 (8) ◽  
pp. 1054-1064 ◽  
Author(s):  
Joseph Burnett ◽  
Bryan Newman ◽  
Duxin Sun
Keyword(s):  
Stem Cells ◽  
Natural Products ◽  
Cancer Stem Cells

scholarly journals Spermatogonia: stem cells with a great perspective

Reproduction ◽  
2001 ◽  
pp. 825-834 ◽  
Author(s):  
S Meachem ◽  
V von Schonfeldt ◽  
S Schlatt
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Research ◽  
Hormonal Regulation ◽  
Male Contraception ◽  
Comprehensive Overview ◽  
Oncological Patients ◽  
Spermatogonia Stem Cells ◽  
New Research ◽  
Near Future

Interest in spermatogonia has grown in recent years as a result of exciting developments in stem cell research in general and the development of new research tools allowing the isolation, culture and transplantation of these cells. This review focuses on the methodological breakthroughs and highlights the recent findings that have substantially increased understanding of spermatogonial physiology. The article provides a comprehensive overview of the hormonal regulation of spermatogonia and presents several new approaches to the use of spermatogonia in basic science and medicine. In the near future these techniques will allow the development of novel routes for the generation of transgenic lifestock, the treatment of infertility, the targeting for male contraception, and an alternative strategy for fertility preservation of oncological patients.

Sign in / Sign up

Export Citation Format

Share Document