scholarly journals Current Perspectives on Phytomedicines targeting Cancer Stem Cells

2021 ◽  
Author(s):  
Mrunmayee Saraff ◽  
Rekha Gahtori ◽  
Surya Tripathi ◽  
Sugapriya Dhanasekaran ◽  
Sanjay Kumar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Efflux Pump ◽  
Cancer Drug ◽  
Molecular Signaling ◽  
Mesenchymal Transition ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Elevated Expression

Studies have established the presence of a small subpopulation of cells within tumor cells, known as cancer stem cells (CSCs). These cells have evidently been the reason for metastasis, chemotherapy or radiotherapy resistance and tumor relapses in several types of cancers. CSCs are prone to epithelial-to-mesenchymal transition (EMT), resulting in aggressive tumors. They modulate various pathways of molecular signaling, including Wnt, Hedgehog and Notch, thus increasing the stem-like characteristics. Elevated expression of ATP binding cassette (ABC) transporter efflux pump as well as suppression of apoptosis has also increased anti-cancer drug resistance. Plants are known to possess bioactive compounds that can modulate these key regulators and hence eliminate CSCs. This review aims to report and summarize preclinical studies about the effects of phytocompounds on CSCs of various tumors. Furthermore, clinical trials carried out for some of these phytoconstituents are reported. Thus, selectively targeting CSCs with plant extracts and herbal preparations may be a promising remedial strategy for cancer.

scholarly journals Phytomedicines Targeting Cancer Stem Cells: Therapeutic Opportunities and Prospects for Pharmaceutical Development

2021 ◽  
Vol 14 (7) ◽  
pp. 676
Author(s):  
Piyush Kumar Gupta ◽  
Mrunmayee Saraff ◽  
Rekha Gahtori ◽  
Nidhi Negi ◽  
Surya Kant Tripathi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial Mesenchymal Transition ◽  
Efflux Pump ◽  
Mesenchymal Transition ◽  
Anti Cancer ◽  
Selective Targeting ◽  
Drug Efflux Pump ◽  
Bioactive Agents ◽  
Preclinical And Clinical Studies

The presence of small subpopulations of cells within tumor cells are known as cancer stem cells (CSCs). These cells have been the reason for metastasis, resistance with chemotherapy or radiotherapy, and tumor relapse in several types of cancers. CSCs underwent to epithelial–mesenchymal transition (EMT) and resulted in the development of aggressive tumors. CSCs have potential to modulate numerous signaling pathways including Wnt, Hh, and Notch, therefore increasing the stem-like characteristics of cancer cells. The raised expression of drug efflux pump and suppression of apoptosis has shown increased resistance with anti-cancer drugs. Among many agents which were shown to modulate these, the plant-derived bioactive agents appear to modulate these key regulators and were shown to remove CSCs. This review aims to comprehensively scrutinize the preclinical and clinical studies demonstrating the effects of phytocompounds on CSCs isolated from various tumors. Based on the available convincing literature from preclinical studies, with some clinical data, it is apparent that selective targeting of CSCs with plants, plant preparations, and plant-derived bioactive compounds, termed phytochemicals, may be a promising strategy for the treatment of relapsed cancers.

Marine Natural Products as a Promising Source of Therapeutic Compounds to Target Cancer Stem Cells

2020 ◽  
Vol 27 ◽  
Author(s):  
Catarina Vizetto-Duarte ◽  
Pedro Castelo Branco ◽  
Luísa Custódio
Keyword(s):  
Stem Cells ◽  
Natural Products ◽  
Cancer Stem Cells ◽  
Marine Natural Products ◽  
Epithelial To Mesenchymal Transition ◽  
Heart Diseases ◽  
The Body ◽  
Mesenchymal Transition ◽  
Anti Cancer ◽  
Promising Source

: Cancer is the world’s second leading cause of death after heart diseases, and involves abnormal cell growth at a primary site and the potential to spread to other parts of the body. Tumors are highly heterogeneous and consist of subgroups of cells with distinct characteristics. Of these, the cancer stem cells (CSC) niche plays a crucial role in driving the spread of the tumor and are thought to provide treatment resistance. CSC is a rare special population of cancer cells exhibiting high tumorigenic properties together with self-renewal and differentiation capability. CSC is not only linked with high tumor-initiating activity, but is also implicated in chemotherapeutic re-sistance, metastasis, epithelial to mesenchymal transition, and recurrence. Thereafter, novel ther-apeutic strategies targeting CSC are in need in order to improve long-term clinical outcome. The literature supports the evidence that marine natural compounds can exhibit antioxidant, antimitot-ic, anti-inflammatory, anti-biotic as well as anticancer activity. In this review, we will provide an insight into the relevance of selected marine natural products as a source of bioactive compounds with anti-cancer properties, and to target CSC, which may benefit the development of novel anti-cancer therapeutic strategies.

scholarly journals The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1239
Author(s):  
Leila Jahangiri ◽  
Tala Ishola ◽  
Perla Pucci ◽  
Ricky M. Trigg ◽  
Joao Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Repair Capacity ◽  
Mesenchymal Transition ◽  
Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

scholarly journals Pivotal Role of AKT2 during Dynamic Phenotypic Change of Breast Cancer Stem Cells

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1058 ◽  
Author(s):  
Gener ◽  
Rafael ◽  
Seras-Franzoso ◽  
Perez ◽  
Pindado ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Distant Metastases ◽  
Metastatic Potential ◽  
Phenotypic Change ◽  
Primary Tumors ◽  
Mesenchymal Transition

Therapeutic resistance seen in aggressive forms of breast cancer remains challenging for current treatments. More than half of the patients suffer from a disease relapse, most of them with distant metastases. Cancer maintenance, resistance to therapy, and metastatic disease seem to be sustained by the presence of cancer stem cells (CSC) within a tumor. The difficulty in targeting this subpopulation derives from their dynamic interconversion process, where CSC can differentiate to non-CSC, which in turn de-differentiate into cells with CSC properties. Using fluorescent CSC models driven by the expression of ALDH1A 1(aldehyde dehydrogenase 1A1), we confirmed this dynamic phenotypic change in MDA-MB-231 breast cancer cells and to identify Serine/Threonine Kinase 2 (AKT2) as an important player in the process. To confirm the central role of AKT2, we silenced AKT2 expression via small interfering RNA and using a chemical inhibitor (CCT128930), in both CSC and non-CSC from different cancer cell lines. Our results revealed that AKT2 inhibition effectively prevents non-CSC reversion through mesenchymal to epithelial transition, reducing invasion and colony formation ability of both, non-CSC and CSC. Further, AKT2 inhibition reduced CSC survival in low attachment conditions. Interestingly, in orthotopic tumor mouse models, high expression levels of AKT2 were detected in circulating tumor cells (CTC). These findings suggest AKT2 as a promising target for future anti-cancer therapies at three important levels: (i) Epithelial-to-mesenchymal transition (EMT) reversion and maintenance of CSC subpopulation in primary tumors, (ii) reduction of CTC and the likelihood of metastatic spread, and (iii) prevention of tumor recurrence through inhibition of CSC tumorigenic and metastatic potential.

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