Targeting cellular senescence in cancer by plant secondary metabolites: A systematic review

Fakhri, Sajad; Moradi, Seyed Zachariah; Ash-Rafzadeh, Angela; Bishayee, Anupam

doi:10.1016/j.phrs.2021.105961

Cited by 23 publications

(17 citation statements)

References 239 publications

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“…The considerable volume of reported data proposed that diets rich in phenolic compounds could decrease the incidence of several cancers. Curcumin (Figure 4) is a well-known phytochemical with several important biological activities, including anticarcinogenic, neuroprotective, anti-inflammatory, and anti-SARS-CoV-2 effects (6,13,(80)(81)(82)(83)(84)(85). Curcumin suppressed the proliferation of MHCC97H liver cancer cells in vitro by promoting the formation of intracellular ROS, increasing apoptosis, and activating caspase-3, caspase-8, and TLR4/MyD-88 signaling (86).…”

Section: Phenolic Compoundsmentioning

confidence: 99%

“…Currently, the most important treatment option for malignant tumors is chemotherapy, which may lead to numerous side effects and promote drug resistance in patients. The use of natural products for the treatment of cancer is not only economically efficient, but also exerts multiple prophylactic, protective, and therapeutic roles in the treatment process that may reduce the side effects of chemotherapy and radiotherapy and decrease drug resistance (6,13,(324)(325)(326).…”

Section: Phytochemicals In Combination With Anticancer Drugs Potentia...mentioning

confidence: 99%

“…Despite the effectiveness of plant secondary metabolites in regulating chemoresistance-associated pathways, their low solubility, poor bioavailability, instability, and low selectivity limit clinical efficacy and therapeutic uses in cancer treatment. The applicability of nanotechnology has greatly improved bioavailability, cellular uptake, efficacy, and specificity of anticancer phytochemicals, thereby overcome those pharmacokinetic limitations ( 6 , 13 , 457 , 481 ). In line with this, liposomes, polymeric nanoparticles, micelles, nanodispersion, nanostructured lipid carriers, and dendrimers of plant secondary metabolites have played pivotal roles in reducing chemoresistance ( 482 ).…”

Section: Conclusion Current Limitations and Future Perspectivesmentioning

confidence: 99%

“…Plant secondary metabolites are multi-targeting anticancer agents that target the cancer-associated pathways, including cellular senescence ( 6 ), Hippo signaling ( 7 ), Wnt/β-catenin ( 8 ), Janus kinase (JAK)/signal transducer and activator of transcription (STAT) ( 9 ), phosphoinositide 3-kinases (PI3K)/Akt/mammalian target of rapamycin (mTOR) ( 10 ), hypoxia-inducible factor-1α (HIF-1α) ( 11 ), and activator protein 1 (AP-1) ( 12 ). Phenolic compounds, alkaloids, terpenes/terpenoids, and sulfur-containing compounds demonstrated anticancer potential by modulating tumorigenic signaling pathways ( 6 , 13 ). Emerging evidence has shown the influence of chemoresistance on cancer therapy ( 5 , 14 , 15 ).…”

Section: Introductionmentioning

confidence: 99%

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Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

et al. 2022

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BackgroundTumors often progress to a more aggressive phenotype to resist drugs. Multiple dysregulated pathways are behind this tumor behavior which is known as cancer chemoresistance. Thus, there is an emerging need to discover pivotal signaling pathways involved in the resistance to chemotherapeutic agents and cancer immunotherapy. Reports indicate the critical role of the toll-like receptor (TLR)/nuclear factor-κB (NF-κB)/Nod-like receptor pyrin domain-containing (NLRP) pathway in cancer initiation, progression, and development. Therefore, targeting TLR/NF-κB/NLRP signaling is a promising strategy to augment cancer chemotherapy and immunotherapy and to combat chemoresistance. Considering the potential of phytochemicals in the regulation of multiple dysregulated pathways during cancer initiation, promotion, and progression, such compounds could be suitable candidates against cancer chemoresistance.ObjectivesThis is the first comprehensive and systematic review regarding the role of phytochemicals in the mitigation of chemoresistance by regulating the TLR/NF-κB/NLRP signaling pathway in chemotherapy and immunotherapy.MethodsA comprehensive and systematic review was designed based on Web of Science, PubMed, Scopus, and Cochrane electronic databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to include papers on TLR/NF-κB/NLRP and chemotherapy/immunotherapy/chemoresistance by phytochemicals.ResultsPhytochemicals are promising multi-targeting candidates against the TLR/NF-κB/NLRP signaling pathway and interconnected mediators. Employing phenolic compounds, alkaloids, terpenoids, and sulfur compounds could be a promising strategy for managing cancer chemoresistance through the modulation of the TLR/NF-κB/NLRP signaling pathway. Novel delivery systems of phytochemicals in cancer chemotherapy/immunotherapy are also highlighted.ConclusionTargeting TLR/NF-κB/NLRP signaling with bioactive phytocompounds reverses chemoresistance and improves the outcome for chemotherapy and immunotherapy in both preclinical and clinical stages.

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Section: Phenolic Compoundsmentioning

confidence: 99%

Section: Phytochemicals In Combination With Anticancer Drugs Potentia...mentioning

confidence: 99%

Section: Conclusion Current Limitations and Future Perspectivesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

et al. 2022

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“…Natural product-derived compounds, especially phytochemicals, have been shown to inhibit various stages of carcinogenesis based on preclinical and clinical studies by affecting the proliferation, cell cycle progression, cell death resistance, energy metabolism, cellular senescence immune response, epithelial to mesenchymal transition, angiogenesis, invasion, migration and metastasis of cancer cells [16,[20][21][22][23][24][25]. Various mechanisms of these anticancer effects include upregulation of genes that detoxify reactive oxygen species (ROS) and main redox hemostasis, inhibition of inflammatory cascades, and modulation of numerous oncogenic and oncosuppressive signaling pathways [26][27][28][29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms

Bajalia

Azzouz

Chism

et al. 2022

Cancers

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Renal cell carcinoma (RCC) is associated with about 90% of renal malignancies, and its incidence is increasing globally. Plant-derived compounds have gained significant attention in the scientific community for their preventative and therapeutic effects on cancer. To evaluate the anticancer potential of phytocompounds for RCC, we compiled a comprehensive and systematic review of the available literature. Our work was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The literature search was performed using scholarly databases such as PubMed, Scopus, and ScienceDirect and keywords such as renal cell carcinoma, phytochemicals, cancer, tumor, proliferation, apoptosis, prevention, treatment, in vitro, in vivo, and clinical studies. Based on in vitro results, various phytochemicals, such as phenolics, terpenoids, alkaloids, and sulfur-containing compounds, suppressed cell viability, proliferation and growth, showed cytotoxic activity, inhibited invasion and migration, and enhanced the efficacy of chemotherapeutic drugs in RCC. In various animal tumor models, phytochemicals suppressed renal tumor growth, reduced tumor size, and hindered angiogenesis and metastasis. The relevant antineoplastic mechanisms involved upregulation of caspases, reduction in cyclin activity, induction of cell cycle arrest and apoptosis via modulation of a plethora of cell signaling pathways. Clinical studies demonstrated a reduced risk for the development of kidney cancer and enhancement of the efficacy of chemotherapeutic drugs. Both preclinical and clinical studies displayed significant promise of utilizing phytochemicals for the prevention and treatment of RCC. Further research, confirming the mechanisms and regulatory pathways, along with randomized controlled trials, are needed to establish the use of phytochemicals in clinical practice.

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Appraisal of Medicinal Plants for Pharmacological Properties

Kocak,

Kaysim

2023

Bioprospecting of Tropical Medicinal Plants

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Targeting cellular senescence in cancer by plant secondary metabolites: A systematic review

Cited by 23 publications

References 239 publications

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms

Appraisal of Medicinal Plants for Pharmacological Properties

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