A Comprehensive Study on the Anti-cancer Effects of Quercetin and Its Epigenetic Modifications in Arresting Progression of Colon Cancer Cell Proliferation

Bhatiya, Meenu; Pathak, Surajit; Jothimani, Ganesan; Duttaroy, Asim K.; Banerjee, Antara

doi:10.1007/s00005-023-00669-w

Cited by 15 publications

(6 citation statements)

References 52 publications

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“…Although it is relatively non-toxic, the main disadvantage of quercetin is its low bioavailability (50). The dose used herein is below ranges reported for many in vitro studies (reporting up to 120 µM (51)(52)(53)). Furthermore, it is unclear how to translate the in vitro dose used for cell culture studies to humans.…”

Section: Discussionmentioning

confidence: 95%

Quercetin enhances decidualization through AKT-ERK-p53 signaling and supports a role for senescence in endometriosis

Delenko,

Xue,

Chatterjee

et al. 2024

Preprint

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Background Patients with endometriosis suffer with chronic pelvic pain and infertility, and from the lack of pharmacologic therapies that consistently halt disease progression. Differences in the endometrium of patients with endometriosis vs. unaffected controls are well-documented. Specifically, shed endometrial tissues (delivered to the pelvic cavity via retrograde menstruation) reveal that a subset of stromal cells exhibiting pro-inflammatory, pro-fibrotic, and pro-senescence-like phenotypes is enhanced in endometriosis patients compared to controls. Additionally, cultured biopsy-derived endometrial stromal cells from endometriosis patients exhibit impaired decidualization, a defined differentiation process required for human embryo implantation and pregnancy. Quercetin, a senolytic agent, shows therapeutic potential for pulmonary fibrosis, a disorder attributed to senescent pulmonary fibroblasts. In rodent models of endometriosis, quercetin shows promise, and quercetin improves decidualization in vitro. However, the exact mechanisms are not completely understood. Therefore, we investigated the effects of quercetin on menstrual effluent-derived endometrial stromal cells from endometriosis patients and unaffected controls to define the signaling pathways underlying quercetin’s effects on endometrial stromal cells. Methods Menstrual effluent-derived endometrial stromal cells were collected and cultured from unaffected controls and endometriosis patients and then, low passage cells were treated with quercetin (25 µM) under basal or standard decidualization conditions. Decidualization responses were analyzed by measuring the production of IGFBP1 and PRL. Also, the effects of quercetin on intracellular cAMP levels and cellular oxidative stress responses were measured. Phosphokinase arrays, western blotting, and flow cytometry methods were performed to define the effects of quercetin on various signaling pathways and the potential mechanistic roles of quercetin. Results Quercetin significantly promotes decidualization of control- and endometriosis-endometrial stromal cells. Quercetin substantially reduces the phosphorylation of multiple signaling molecules in the AKT and ERK1/2 pathways, while enhancing the phosphorylation of p53 and total p53 levels. Furthermore, p53 inhibition blocks decidualization while p53 activation promotes decidualization. Finally, we provide evidence that quercetin increases apoptosis of endometrial stromal cells with a senescent-like phenotype. Conclusions These data provide insight into the mechanisms of action of quercetin on endometrial stromal cells and warrant future clinical trials to test quercetin and other senolytics for treating endometriosis.

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Section: Discussionmentioning

confidence: 95%

Quercetin enhances decidualization through AKT-ERK-p53 signaling and supports a role for senescence in endometriosis

Delenko,

Xue,

Chatterjee

et al. 2024

Preprint

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“…Quercetin inhibited the proliferation of colon cancer cells in a dose‐dependent manner by regulating the expression of SIRT6 and Klotho, inhibiting telomerase activity, and safeguarding DNA integrity (Bhatiya et al, 2023). Quercetin demonstrated chemopreventive and therapeutic activity in a 7,12‐dimethylbenz[a]anthracene‐induced hamster buccal pouch carcinoma model.…”

Section: Sirt‐mediated Therapeutic Effects Of Quercetinmentioning

confidence: 99%

Exploring the therapeutic potential of quercetin: A focus on its sirtuin‐mediated benefits

Ungurianu,

Zanfirescu,

Margină

2024

Phytotherapy Research

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As the global population ages, preventing lifestyle‐ and aging‐related diseases is increasing, necessitating the search for safe and affordable therapeutic interventions. Among nutraceuticals, quercetin, a flavonoid ubiquitously present in various plants, has garnered considerable interest. This review aimed to collate and analyze existing literature on the therapeutic potentials of quercetin, especially its interactions with SIRTs and its clinical applicability based on its bioavailability and safety. This narrative review was based on a literature survey spanning from 2015 to 2023 using PUBMED. The keywords and MeSH terms used were: “quercetin” AND “bioavailability” OR “metabolism” OR “metabolites” as well as “quercetin” AND “SIRTuin” OR “SIRT*” AND “cellular effects” OR “pathway” OR “signaling” OR “neuroprotective” OR “cardioprotective” OR “nephroprotective” OR “antiatherosclerosis” OR “diabetes” OR “antidiabetic” OR “dyslipidemia” AND “mice” OR “rats”. Quercetin demonstrates multiple therapeutic activities, including neuroprotective, cardioprotective, and anti‐atherosclerotic effects. Its antioxidant, anti‐inflammatory, antiviral, and immunomodulatory properties are well‐established. At a molecular level, it majorly interacts with SIRTs, particularly SIRT1 and SIRT6, and modulates numerous signaling pathways, contributing to its therapeutic effects. These pathways play roles in reducing oxidative stress, inflammation, autophagy regulation, mitochondrial biogenesis, glucose utilization, fatty acid oxidation, and genome stability. However, clinical trials on quercetin's effectiveness in humans are scarce. Quercetin exhibits a wide range of SIRT‐mediated therapeutic effects. Despite the compelling preclinical data, more standardized clinical trials are needed to fully understand its therapeutic potential. Future research should focus on addressing its bioavailability and safety concerns.

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“…The antitumor aspect involves breast cancer, liver cancer, colon cancer, etc. [ 65 , 66 , 67 , 68 , 69 , 70 ]. However, there are application limitations related to the stability of use in vivo, which limits the use of quercetin [ 71 ].…”

Section: Polyphenolic Compoundsmentioning

confidence: 99%

Dendrimers as Nanocarriers for the Delivery of Drugs Obtained from Natural Products

Deng

Wang

et al. 2023

Polymers

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Natural products have proven their value as drugs that can be therapeutically beneficial in the treatment of various diseases. However, most natural products have low solubility and poor bioavailability, which pose significant challenges. To solve these issues, several drug nanocarriers have been developed. Among these methods, dendrimers have emerged as vectors for natural products due to their superior advantages, such as a controlled molecular structure, narrow polydispersity index, and the availability of multiple functional groups. This review summarizes current knowledge on the structures of dendrimer-based nanocarriers for natural compounds, with a particular focus on applications in alkaloids and polyphenols. Additionally, it highlights the challenges and perspectives for future development in clinical therapy.

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A Comprehensive Study on the Anti-cancer Effects of Quercetin and Its Epigenetic Modifications in Arresting Progression of Colon Cancer Cell Proliferation

Cited by 15 publications

References 52 publications

Quercetin enhances decidualization through AKT-ERK-p53 signaling and supports a role for senescence in endometriosis

Quercetin enhances decidualization through AKT-ERK-p53 signaling and supports a role for senescence in endometriosis

Exploring the therapeutic potential of quercetin: A focus on its sirtuin‐mediated benefits

Dendrimers as Nanocarriers for the Delivery of Drugs Obtained from Natural Products

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