Targeting Cancer Stem Cells with Natural Products

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.

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Multidrug-resistant cancer cells and cancer stem cells hijack cellular systems to circumvent systemic therapies, can natural products reverse this?

Cellular and Molecular Life Sciences ◽

10.1007/s00018-016-2362-3 ◽

2016 ◽

Vol 74 (5) ◽

pp. 777-801 ◽

Cited By ~ 13

Author(s):

Qian Zhang ◽

Yunjiang Feng ◽

Derek Kennedy

Keyword(s):

Stem Cells ◽

Natural Products ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Multidrug Resistant ◽

Cellular Systems ◽

Systemic Therapies

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Natural Products Targeting Cancer Stem Cells for Augmenting Cancer Therapeutics

International Journal of Molecular Sciences ◽

10.3390/ijms222313044 ◽

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.

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

Current Pharmaceutical Design ◽

10.2174/1381612825666190111124822 ◽

2019 ◽

Vol 24 (36) ◽

pp. 4251-4269 ◽

Cited By ~ 12

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.

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

Current Medicinal Chemistry ◽

10.2174/0929867328666210628131409 ◽

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.

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Targeting Multiple Myeloma Cancer Stem Cells with Natural Products – Lessons from Other Hematological Malignancies

Planta Medica ◽

10.1055/s-0043-109558 ◽

2017 ◽

Vol 83 (09) ◽

pp. 752-760 ◽

Cited By ~ 5

Author(s):

Mark Issa ◽

Sylvian Cretton ◽

Muriel Cuendet

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Natural Products ◽

Cancer Stem Cells ◽

Hematological Malignancies ◽

Plasma Cells ◽

Chemical Structures ◽

Recent Advances ◽

Promising Therapeutic Approach

AbstractMultiple myeloma is characterized by the accumulation of malignant plasma cells in the bone marrow. Multiple myeloma is the second most frequently diagnosed hematological malignancy, predominantly affecting the elderly. Despite recent advances in the development of novel therapies, multiple myeloma remains an incurable malignancy where the majority of patients relapse, develop resistance, and eventually die from the disease. This has been attributed to the fact that conventional therapy currently in use targets mainly the bulk of tumor cells, but not the tumor-initiating cancer stem cells. Cancer stem cells are a highly resistant subpopulation of cells believed to be responsible for the initiation, progression, metastasis, and relapse of cancer. Enormous efforts have been invested in the characterization of cancer stem cells. These efforts led to the characterization of key cellular signaling pathways responsible for conferring stem cell characteristics including self-renewal, differentiation, migratory, survival, and intracellular detoxification capabilities. Targeting these protective mechanisms offers a valuable strategy that may help combat a major driving force behind cancers. The use of natural products offers a promising therapeutic approach for targeting cancer stem cells. In this review, recent advances achieved in the characterization of cancer stem cells derived from hematological malignancies, with a particular focus on multiple myeloma, are discussed and major natural products that target cancer stem cells are presented. As natural products remain an essential source of novel chemical structures and medicinal leads, the exploitation of this immense reservoir is used to draw lessons in targeting multiple myeloma-cancer stem cells.

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

Current Medicinal Chemistry ◽

10.2174/0929867327666200320155053 ◽

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.

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