Enhancement of glioblastoma multiforme therapy through a novel Quercetin-Losartan hybrid

Tsiailanis, Antonis D.; Renziehausen, Alexander; Kiriakidi, Sofia; Vrettos, Eirinaios I.; Μαρκόπουλος, Γεώργιος; Sayyad, Nisar; Hirmiz, Baydaa; Aguilar, Marie‐Isabel; Borgo, Mark P. Del; Kolettas, Evangelos; Widdop, Robert E; Mavromoustakos, Thomas; Crook, Tim; Syed, Nelofer; Tzakos, Andreas G.

doi:10.1016/j.freeradbiomed.2020.08.007

Cited by 20 publications

(13 citation statements)

References 69 publications

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“…Recently, it was reported that quercetin reverses the irregular DNA methylation patterns of different cancer cells and thus also exerts anticancer activities through epigenetic modifications. , Quercetin decreases the population of tumor-initiating cells through the modulation of the death-associated factor 6 (DAXX) protein . Interestingly, when used in combination, quercetin increases the efficiencies of other anticancer molecules like losartan, paclitaxel, and resveratrol in different cancers. − The nanoformulations of quercetin are very effective against different cancers including lung, liver, breast, and glioblastomas. ,, These studies reported the anticancer properties of quercetin, but the exact mechanism of its action remains elusive, and this study is the first of its kind that investigated the potential of quercetin as an inhibitor of CDK6.…”

Section: Introductionmentioning

confidence: 99%

Inhibiting CDK6 Activity by Quercetin Is an Attractive Strategy for Cancer Therapy

et al. 2020

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Cyclin-dependent kinase 6 (CDK6) is a potential drug target that plays an important role in the progression of different types of cancers. We performed in silico and in vitro screening of different natural compounds and found that quercetin has a high binding affinity for the CDK6 and inhibits its activity with an IC 50 = 5.89 μM. Molecular docking and a 200 ns whole atom simulation of the CDK6-quercetin complex provide insights into the binding mechanism and stability of the complex. Binding parameters ascertained by fluorescence and isothermal titration calorimetry studies revealed a binding constant in the range of 10 7 M –1 of quercetin to the CDK6. Thermodynamic parameters associated with the formation of the CDK6–quercetin complex suggested an electrostatic interaction-driven process. The cell-based protein expression studies in the breast (MCF-7) and lung (A549) cancer cells revealed that the treatment of quercetin decreases the expression of CDK6. Quercetin also decreases the viability and colony formation potential of selected cancer cells. Moreover, quercetin induces apoptosis, by decreasing the production of reactive oxygen species and CDK6 expression. Both in silico and in vitro studies highlight the significance of quercetin for the development of anticancer leads in terms of CDK6 inhibitors.

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Section: Introductionmentioning

confidence: 99%

Inhibiting CDK6 Activity by Quercetin Is an Attractive Strategy for Cancer Therapy

et al. 2020

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“… 20 , 21 Quercetin in combination with losartan has recently shown promising benefit in survival. 22 Antioxidants may further increase sensitivity to radiotherapy. Whereas antioxidant supplements might provide some protection from radiation-induced brain injury 23 or even increased sensitization to treatment, precautions must be taken because of the potential reduction of therapeutic effects, possibly resulting in a higher risk of recurrence.…”

Section: Discussionmentioning

confidence: 99%

Use of Complementary and Integrative Medicine Among Patients With Glioblastoma Multiforme Seen at a Tertiary Care Center

Munoz-Casabella

Wahner‐Roedler

Croghan

et al. 2022

Glob Adv Health Med

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Background Glioblastoma multiforme (GBM) is among the most aggressive and lethal tumors, with a median survival of 12–15 months. Many patients use complementary and integrative medicine (CIM) therapies to supplement their cancer treatment. Objective To determine the prevalence of CIM use and identify the most frequently used types of CIM in a cohort of patients with GBM seen at a tertiary care medical center in the United States. Methods An anonymous survey was mailed through the US Postal Service from August 1, 2019, through February 21, 2020, to patients with GBM. Results A total of 346 surveys were mailed, and 146 responses (42%) were received. The median age of respondents was 61 years (range, 52–68 years), and 85 (58%) were male. Most patients had undergone surgery (90%), chemotherapy (96%), and radiotherapy (95%). The median time from diagnosis of GBM to survey participation was 18 months (range, 12–31 months). Most respondents (81%) used some form of CIM, most frequently meditation (22%), relaxation and other stress management techniques (19%), chiropractic therapy (16%), and acupuncture (12%). Compared with men, women more commonly meditated (32% vs 16%; P = .046) and practiced yoga (20% vs 6%; P = .04). We observed age-based differences, with younger patients more commonly meditating, practicing relaxation and stress management techniques, and receiving chiropractic therapy ( P < .05 for all). Conclusions Providers should encourage patients with GBM to discuss their interest in CIM therapies and guide them to evidence-based treatments that may help improve their quality of life.

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“…Theranostic agents can be composed of various linkers tethering the individual components conferring the required properties, for example, water solubility (i.e., sulfonate groups), bioavailability (i.e., polyethylene glycol (PEG) groups), and stability in biofluids, such as blood (i.e., non-cleavable bonds). Linkers play a crucial role within bioconjugates and their manipulation might interfere (positively or negatively) with the overall bioactivity profile of the conjugate [18,[65][66][67][68][69]. Finally, molecules can be encapsulated or organized into micelles, nanoparticles, and other complex nanoformulations [70].…”

Section: Design Strategies For Cancer Theranostics With Photoacoustic...mentioning

confidence: 99%

Design Principles Governing the Development of Theranostic Anticancer Agents and Their Nanoformulations with Photoacoustic Properties

et al. 2022

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The unmet need to develop novel approaches for cancer diagnosis and treatment has led to the evolution of theranostic agents, which usually include, in addition to the anticancer drug, an imaging agent based mostly on fluorescent agents. Over the past few years, a non-invasive photoacoustic imaging modality has been effectively integrated into theranostic agents. Herein, we shed light on the design principles governing the development of theranostic agents with photoacoustic properties, which can be formulated into nanocarriers to enhance their potency. Specifically, we provide an extensive analysis of their individual constituents including the imaging dyes, drugs, linkers, targeting moieties, and their formulation into nanocarriers. Along these lines, we present numerous relevant paradigms. Finally, we discuss the clinical relevance of the specific strategy, as also the limitations and future perspectives, and through this review, we envisage paving the way for the development of theranostic agents endowed with photoacoustic properties as effective anticancer medicines.

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Enhancement of glioblastoma multiforme therapy through a novel Quercetin-Losartan hybrid

Cited by 20 publications

References 69 publications

Inhibiting CDK6 Activity by Quercetin Is an Attractive Strategy for Cancer Therapy

Inhibiting CDK6 Activity by Quercetin Is an Attractive Strategy for Cancer Therapy

Use of Complementary and Integrative Medicine Among Patients With Glioblastoma Multiforme Seen at a Tertiary Care Center

Design Principles Governing the Development of Theranostic Anticancer Agents and Their Nanoformulations with Photoacoustic Properties

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