Dietary Phytochemicals as a Potential Source for Targeting Cancer Stem Cells

Manogaran, Prasath; Umapathy, Devan; Karthikeyan, Manochitra; Venkatachalam, Karthikkumar; Singaravelu, Anbu

doi:10.1080/07357907.2021.1894569

Cited by 10 publications

(16 citation statements)

References 98 publications

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“…The inhibition of select stem cell markers provides potential mechanistic leads for the efficacy of efficacious natural products. Consistent with this evidence it is notable that several mechanistically distinct naturally-occurring compounds have documented stem cell specific inhibitory effects [51][52][53][54][55].…”

Section: Effect Of Curcumin On Stem Cellsmentioning

confidence: 71%

“…The cellular models are developed from genetically predisposed colonic epithelium [23,24,27], stem cell models are developed from drug-resistant colonic epithelial cells [19,21,22], and tumor spheroid models are developed either from patient derived cancer stem cell-enriched spheroids [39,40] or from sporadic cancer derived cell lines [44,45]. Experimental modulations are quantified by specific Consistent with this evidence it is notable that several mechanistically distinct naturallyoccurring compounds have documented stem cell specific inhibitory effects [51][52][53][54][55].…”

Section: Discussionmentioning

confidence: 99%

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Drug-Resistant Stem Cells: Novel Approach for Colon Cancer Therapy

Telang¹

2022

IJMS

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Background: Next to breast cancer, advanced stage metastatic colon cancer represents a major cause for mortality in women. Germline or somatic mutations in tumor suppressor genes or in DNA mismatch repair genes represent risk factors for genetic predisposition of colon cancer that are also detectable in sporadic colon cancer. Conventional chemotherapy for colon cancer includes combination of 5-fluoro-uracil with oxaliplatin and irinotecan or targeted therapy with non-steroid anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors. Major limitations of these therapeutic interventions are associated with systemic toxicity, acquired tumor resistance and the emergence of drug resistant stem cells that favor initiation, progression and metastasis of therapy-resistant disease. These limitations emphasize an unmet need to identify tumor stem cell selective testable alternatives. Drug-resistant stem cell models facilitate the identification of new testable alternatives from natural phytochemicals and herbal formulations. The goal of this review is to provide an overview relevant to the current status of conventional/targeted therapy, the role of cancer stem cells and the status of testable alternatives for therapy-resistant colon cancer. Experimental models: Hyper-proliferative and tumorigenic cell lines from genetically predisposed colonic tissues of female mice represent experimental models. Chemotherapeutic agents select drug-resistant phenotypes that exhibit upregulated expressions of cellular and molecular stem cell markers. Mechanistically distinct natural phytochemicals effectively inhibit stem cell growth and downregulate the expressions of stem cell markers. Conclusions: The present review discusses the status of colon cancer therapy and inherent limitations, cancer stem cell biology, potential lead compounds and their advantages over chemotherapy. The present experimental approaches will facilitate the identification of pharmacological and naturally-occurring agents as lead compounds for stem cell targeted therapy of colon cancer.

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Section: Effect Of Curcumin On Stem Cellsmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Drug-Resistant Stem Cells: Novel Approach for Colon Cancer Therapy

Telang¹

2022

IJMS

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“…Recently, the use of natural products as adjuvants with other chemotherapeutic agents gained medical importance to enhance the chemotherapeutic efficacy of anticancer agents against various cancer cells. [ 8 ] Natural anticancer compounds such as topotecan, irinotecan, and polysaccharide K are approved by FDA for clinical use in combination with chemotherapy against CRC. [ 8 ] In this context, the present study is focused to induce chemosensitization with neferine/isoliensinine treatment or combinatorial regimen against CSCs.…”

Section: Discussionmentioning

confidence: 99%

“…[ 8 ] Natural anticancer compounds such as topotecan, irinotecan, and polysaccharide K are approved by FDA for clinical use in combination with chemotherapy against CRC. [ 8 ] In this context, the present study is focused to induce chemosensitization with neferine/isoliensinine treatment or combinatorial regimen against CSCs.…”

Section: Discussionmentioning

confidence: 99%

“…Natural compounds such as isolated phytochemicals are being used as adjutants along with chemotherapy against cancer. [ 7,8 ] Past reports described the efficacy of several phytochemicals in mediating the reversal of multidrug resistance (MDR). For instance, curcumin could alleviate the MDR in the vincristine‐resistant colon and gastric cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Reversal of cisplatin resistance by neferine/isoliensinine and their combinatorial regimens with cisplatin‐induced apoptosis in cisplatin‐resistant colon cancer stem cells (CSCs)

Manogaran

Somasundaram

Viswanadha

2021

J Biochem & Molecular Tox

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Cisplatin chemotherapy to the colorectal cancer cells (CRCs) is accompanied by dose‐limiting adverse effects along with the acquisition of drug resistance implicating low therapeutic outcomes. The present study is aimed to evaluate the chemosensitizing efficacy of neferine/isoliensinine or combinatorial regimen of neferine/isoliensinine with cisplatin against CSCs (cisplatin resistant colon stem cells). CSCs were developed using pulse exposure of cisplatin to parental HCT‐15 cells. Neferine/isoliensinine or combinatorial regimens of Neferine/isoliensinine and cisplatin exhibited a stronger cytotoxic activity against CSCs compared to control. IC50 doses were found to be 6.5 μM for neferine, 12.5 μM for isoliensinine, and 120 μM for cisplatin respectively. Furthermore, the combinatorial regimen of a low dose of cisplatin (40 μM) with 4 μM neferine/8 μM isoliensinine induced cell death in a synergistic manner as described by isobologram. Neferine/isoliensinine could confer extensive intracellular reactive oxygen species generation in CSCs. Neferine/isoliensinine or combinatorial regimens dissipated mitochondrial membrane potential and enhanced intracellular [Ca2+]i, which were measured by spectroflurimetry. Furthermore, these combinatorial regimens induced a significant increase in the sub G0 phase of cell cycle arrest and PI uptake and alleviated the expression of ERCC1 in CSCs. Combinatorial regimens or neferine/isoliensinine treatments downregulated the cell survival protein expression (PI3K/pAkt/mTOR) and activated mitochondria‐mediated apoptosis by upregulating Bax, cytochrome c, caspase‐3, and PARP cleavage expression while downregulating the BCl‐2 expression in CSCs. Our study confirms the chemosensitizing efficacy of neferine/isoliensinine or combinatorial regimens of neferine/isoliensinine with a low dose of cisplatin against CSCs.

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The efficacy of natural bioactive compounds against prostate cancer: Molecular targets and synergistic activities

Mia,

Dey,

Sakib

et al. 2023

Phytotherapy Research

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Globally, prostate cancer (PCa) is regarded as a challenging health issue, and the number of PCa patients continues to rise despite the availability of effective treatments in recent decades. The current therapy with chemotherapeutic drugs has been largely ineffective due to multidrug resistance and the conventional treatment has restricted drug accessibility to malignant tissues, necessitating a higher dosage resulting in increased cytotoxicity. Plant‐derived bioactive compounds have recently attracted a great deal of attention in the field of PCa treatment due to their potent effects on several molecular targets and synergistic effects with anti‐PCa drugs. This review emphasizes the molecular mechanism of phytochemicals on PCa cells, the synergistic effects of compound‐drug interactions, and stem cell targeting for PCa treatment. Some potential compounds, such as curcumin, phenethyl‐isothiocyanate, fisetin, baicalein, berberine, lutein, and many others, exert an anti‐PCa effect via inhibiting proliferation, metastasis, cell cycle progression, and normal apoptosis pathways. In addition, multiple studies have demonstrated that the isolated natural compounds: d‐limonene, paeonol, lanreotide, artesunate, and bicalutamide have potential synergistic effects. Further, a significant number of natural compounds effectively target PCa stem cells. However, further high‐quality studies are needed to firmly establish the clinical efficacy of these phytochemicals against PCa.

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Dietary Phytochemicals as a Potential Source for Targeting Cancer Stem Cells

Cited by 10 publications

References 98 publications

Drug-Resistant Stem Cells: Novel Approach for Colon Cancer Therapy

Drug-Resistant Stem Cells: Novel Approach for Colon Cancer Therapy

Reversal of cisplatin resistance by neferine/isoliensinine and their combinatorial regimens with cisplatin‐induced apoptosis in cisplatin‐resistant colon cancer stem cells (CSCs)

The efficacy of natural bioactive compounds against prostate cancer: Molecular targets and synergistic activities

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