Natural Compounds in Cancer Therapy: Revealing the Role of Flavonoids in Renal Cell Carcinoma Treatment

Renal cell carcinoma (RCC) is the most lethal malignancy of the urinary system, with limited treatment options due to drug resistance and the adverse effects associated with current therapies. This review aims to systematically examine the therapeutic potential of flavonoids, which are natural polyp...

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Main Authors: Zixuan Chen, Min Liu
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/5/620
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author Zixuan Chen
Min Liu
author_facet Zixuan Chen
Min Liu
author_sort Zixuan Chen
collection DOAJ
description Renal cell carcinoma (RCC) is the most lethal malignancy of the urinary system, with limited treatment options due to drug resistance and the adverse effects associated with current therapies. This review aims to systematically examine the therapeutic potential of flavonoids, which are natural polyphenolic compounds possessing anti-inflammatory, antioxidant, and anticancer properties, in the context of RCC treatment. We summarize the anticancer activities of 26 natural flavonoids, classified into six subclasses, and explore their mechanisms of action, including the inhibition of tumor cell proliferation, migration, and invasion, as well as the induction of apoptosis, autophagy, and ferroptosis. Particular attention is paid to their modulation of key signaling pathways such as the JAK/STAT3, PI3K/Akt/mTOR, and miRNA-related axes, including miR-21/YAP1 and miR-324-3p/GPX4, providing a molecular basis for their anti-RCC activity. We also address several pharmacological challenges that limit the clinical application of flavonoids, including poor bioavailability, metabolic instability, and potential toxicity. Emerging solutions such as novel flavonoid derivatives, advanced drug delivery systems, and rational combination therapy strategies are also discussed. Current clinical evidence, including a phase II trial of flavopiridol in advanced RCC, highlights the potential but also the need for further validation. In conclusion, flavonoids offer a promising approach to improving RCC treatment. Future research should focus on optimizing their therapeutic efficacy and ensuring their safe clinical translation, with the goal of achieving personalized and minimally invasive cancer therapies.
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spelling doaj-art-fd0bc181255c4f22bfb694d24cc4e4082025-08-20T03:47:48ZengMDPI AGBiomolecules2218-273X2025-04-0115562010.3390/biom15050620Natural Compounds in Cancer Therapy: Revealing the Role of Flavonoids in Renal Cell Carcinoma TreatmentZixuan Chen0Min Liu1Department of Urology, Tongren Hospital Shanghai Jiao Tong University School of Medicine, Shanghai 200336, ChinaDepartment of Urology, Tongren Hospital Shanghai Jiao Tong University School of Medicine, Shanghai 200336, ChinaRenal cell carcinoma (RCC) is the most lethal malignancy of the urinary system, with limited treatment options due to drug resistance and the adverse effects associated with current therapies. This review aims to systematically examine the therapeutic potential of flavonoids, which are natural polyphenolic compounds possessing anti-inflammatory, antioxidant, and anticancer properties, in the context of RCC treatment. We summarize the anticancer activities of 26 natural flavonoids, classified into six subclasses, and explore their mechanisms of action, including the inhibition of tumor cell proliferation, migration, and invasion, as well as the induction of apoptosis, autophagy, and ferroptosis. Particular attention is paid to their modulation of key signaling pathways such as the JAK/STAT3, PI3K/Akt/mTOR, and miRNA-related axes, including miR-21/YAP1 and miR-324-3p/GPX4, providing a molecular basis for their anti-RCC activity. We also address several pharmacological challenges that limit the clinical application of flavonoids, including poor bioavailability, metabolic instability, and potential toxicity. Emerging solutions such as novel flavonoid derivatives, advanced drug delivery systems, and rational combination therapy strategies are also discussed. Current clinical evidence, including a phase II trial of flavopiridol in advanced RCC, highlights the potential but also the need for further validation. In conclusion, flavonoids offer a promising approach to improving RCC treatment. Future research should focus on optimizing their therapeutic efficacy and ensuring their safe clinical translation, with the goal of achieving personalized and minimally invasive cancer therapies.https://www.mdpi.com/2218-273X/15/5/620renal cell carcinomanatural productsflavonoidsdrug discoverycombination therapy
spellingShingle Zixuan Chen
Min Liu
Natural Compounds in Cancer Therapy: Revealing the Role of Flavonoids in Renal Cell Carcinoma Treatment
Biomolecules
renal cell carcinoma
natural products
flavonoids
drug discovery
combination therapy
title Natural Compounds in Cancer Therapy: Revealing the Role of Flavonoids in Renal Cell Carcinoma Treatment
title_full Natural Compounds in Cancer Therapy: Revealing the Role of Flavonoids in Renal Cell Carcinoma Treatment
title_fullStr Natural Compounds in Cancer Therapy: Revealing the Role of Flavonoids in Renal Cell Carcinoma Treatment
title_full_unstemmed Natural Compounds in Cancer Therapy: Revealing the Role of Flavonoids in Renal Cell Carcinoma Treatment
title_short Natural Compounds in Cancer Therapy: Revealing the Role of Flavonoids in Renal Cell Carcinoma Treatment
title_sort natural compounds in cancer therapy revealing the role of flavonoids in renal cell carcinoma treatment
topic renal cell carcinoma
natural products
flavonoids
drug discovery
combination therapy
url https://www.mdpi.com/2218-273X/15/5/620
work_keys_str_mv AT zixuanchen naturalcompoundsincancertherapyrevealingtheroleofflavonoidsinrenalcellcarcinomatreatment
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