Myricetin inhibits breast and lung cancer cells proliferation via inhibiting MARK4

Abstract

Identifying novel molecules as potential kinase inhibitors are gaining significant attention globally. The present study suggests Myricetin as a potential inhibitor of microtubule‐affinity regulating kinase (MARK4), adding another molecule to the existing list of anticancer therapeutics. MARK4 regulates initial cell division steps and is a potent druggable target for various cancers. Structure‐based docking with 100 ns molecular dynamics simulation depicted activity of Myricetin in the active site pocket of MARK4 and the formation of a stable complex. The fluorescence‐based assay showed excellent affinity of Myricetin to MARK4 guided by static and dynamic quenching. Moreover, the assessment of enthalpy change (∆H) and entropy change (∆S) delineated electrostatic interactions as a dominant force in the MARK4‐myricetin interaction. Isothermal titration calorimetric measurements revealed spontaneous binding of Myricetin with MARK4. Further, the kinase assay depicted significant inhibition of MARK4 by Myricetin with IC50 = 3.11 µM. Additionally, cell proliferation studies established that Myricetin significantly inhibited the cancer cells (MCF‐7 and A549) proliferation, and inducing apoptosis. This study provides a solid rationale for developing Myricetin as a promising anticancer molecule in the MARK4 mediated malignancies.

Binding Studies of Caffeic and p-Coumaric Acid with α-Amylase: Multispectroscopic and Computational Approaches Deciphering the Effect on Advanced Glycation End Products (AGEs)

“…All these binding experiments were conducted at physiological pH of 7.4. The obtained quenching data were put into Stern-Volmer (Equation ( 1)) and modified Stern-Volmer equation (Equation ( 2)) as per earlier published literature [20,21,36] to find various binding parameters. The binding experiment was performed at physiological pH of 7.4.…”

“…Investigations have shown that α-amylase inhibition aids in regulating glucose levels [17]. Polyphenols, their derivatives and other naturally derived compounds show therapeutic potential against various diseases such as cancer [18][19][20][21], neurodegenerative disorders [22,23], diabetes [24,25] and many more.…”

Cinnamomum zeylanicum Extract and its Bioactive Component Cinnamaldehyde Show Anti-Tumor Effects via Inhibition of Multiple Cellular Pathways

“…Natural products are extensively used to target cancer therapy with minimal side effects ( Anwar et al, 2020a ; Anwar et al, 2020b ; Anjum et al, 2021 ; Anwar et al, 2021 ; Anwar et al, 2022a ; Anwar et al, 2022b ; Anwar et al, 2022c ). Cinnamomum zeylanicum (CZ) is a tropical evergreen plant belonging to the genus Cinnamomum.…”

Expression of Irisin/FNDC5 in Breast Cancer

“…BC is often detected in its advanced stages when the available treatment is not very effective [ 1 ]. There are many studies that have searched for new methods of BC treatment, e.g., by inhibiting kinases such as MARK4 [ 2 , 3 ]; however, there is still a need to search for new potential drugs and prognostic and predictive markers for BC. Recent studies on BC and other cancer types have indicated that irisin could be one such potential marker.…”