Dual mode of binding of anti cancer drug epirubicin to G-quadruplex [d-(TTAGGGT)]4 containing human telomeric DNA sequence induces thermal stabilization

Raje, Shailja; Pandav, Kumud; Barthwal, Ritu

doi:10.1016/j.bmc.2019.115131

Cited by 11 publications

(4 citation statements)

References 85 publications

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“…EPI is an anthracycline that can be used to treat breast cancer and exhibits the anti-cancer effect by intercalating into DNA strands to block DNA and RNA synthesis and inhibition of topoisomerase II [ 19 ]. However, the application of EPI in the treatment of cancer has been limited due to its serious adverse side effects, particularly dose-related cardiotoxicity, which can cause irreversible congestive cardiac failure in patients [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Ursolic Acid Enhances the Sensitivity of MCF-7 and MDA-MB-231 Cells to Epirubicin by Modulating the Autophagy Pathway

et al. 2022

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Breast cancer is the leading cause of cancer death among women in the world, and its morbidity and mortality are increasing year by year. Epirubicin (EPI) is a commonly used drug for the treatment of breast cancer but unfortunately can cause cardiac toxicity in patients because of dose accumulation. Therefore, there is an urgent need for new therapies to enhance the sensitivity of breast cancer cells to EPI. In this study, we found ursolic acid (UA) can significantly improve the drug sensitivity of human breast cancer MCF-7/MDA-MB-231 cells to EPI. Next, we observed that the co-treatment of UA and EPI can up-regulate the expression of autophagy-related proteins Beclin-1, LC3-II/LC3-I, Atg5, and Atg7, and decrease the expression levels of PI3K and AKT, which indicates that the potential mechanism should be carried out by the regulating class III PI3K(VPS34)/Beclin-1 pathway and PI3K/AKT/mTOR pathway. Furthermore, we found the autophagy inhibitor 3-methyladenine (3-MA) could significantly reverse the inhibitory effect of co-treatment of UA and EPI on MCF-7 and MDA-MB-231 cells. These findings indicate that UA can dramatically enhance the sensitivity of MCF-7 and MDA-MB-231 cells to EPI by modulating the autophagy pathway. Our study may provide a new therapeutic strategy for combination therapy.

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Section: Discussionmentioning

confidence: 99%

Ursolic Acid Enhances the Sensitivity of MCF-7 and MDA-MB-231 Cells to Epirubicin by Modulating the Autophagy Pathway

et al. 2022

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“…Similarly, some TOP2 inhibitory molecules have been shown to possess G4 stabilization capacities (77)(78)(79)(80).…”

Section: Discussionmentioning

confidence: 99%

Transcription-associated topoisomerase activities control DNA-breaks production by G-quadruplex ligands

Pipier

Bossaert

Riou

et al. 2020

Preprint

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G-quadruplexes (G4), non-canonical DNA structures, are involved in several essential processes. Stabilization of G4 structures by small compounds (G4 ligands) affects almost all DNA transactions, including telomere maintenance and genomic stability. Here, thanks to a powerful and unbiased genetic approach, we identify topoisomerase 2-alpha (TOP2A) as the main effector of cell cytotoxicity induced by CX5461, a G4 ligand currently undergoing phase I/II clinical trials. This approach also allowed to identify new point mutations affecting TOP2A activity without compromising cell viability. Moreover, based on cross-resistance studies and siRNA-based protein depletion we report that TOP2A plays a major role in cell cytotoxicity induced by two unrelated clastogenic G4 ligands, CX5461 and pyridostatin (PDS). We also report that cytotoxic effects induced by both compounds are associated with topoisomerase 2mediated DNA breaks production. Finally, we show that TOP2-mediated DNA breaks production is strongly associated with RNA Pol II-dependent transcription and is countered by topoisomerase 1 (TOP1). Altogether our results indicate that clastogenic G4 ligands act as DNA structure-driven TOP2-poisons at transcribed regions bearing G-quadruplex structures.

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“…On the other hand, knowing that G-quadruplexes in proto-oncogenic or telomeric regions of the genome play significant roles in cancer progression, the classical antitumor drugs that interact with DNA have been tested to check their ability to bind with G4s [ 25 ]. For example, anticancer drugs, such as epirubicin [ 47 ] and adriamycin [ 48 ], bind as monomers to telomeric G4 with a high affinity. Therefore, in terms of the potential therapeutic application of G4s, recognizing ligands is necessary for them to be able to distinguish between different G4 topologies [ 49 ].…”

Section: Introductionmentioning

confidence: 99%

Interaction of 9-Methoxyluminarine with Different G-Quadruplex Topologies: Fluorescence and Circular Dichroism Studies

Nowak-Karnowska

Głuszyńska

Kosman

et al. 2021

IJMS

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The interactions of G–quadruplexes of different topologies with highly fluorescent 9-methoxyluminarine ligand 9-MeLM were investigated by fluorescence and circular dichroism spectroscopy. The results showed that 9-methoxyluminarine was able to interact and did not destabilize any investigated molecular targets. The studied compound was selectively quenched by parallel c-MYC G-quadruplex DNA, whereas hybrid and antiparallel G4 topology caused only a negligible decrease in the fluorescence of the ligand. A high decrease of fluorescence of the ligand after binding with c-MYC G-quadruplex suggests that this molecule can be used as a selective probe for parallel G-quadruplexes.

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Dual mode of binding of anti cancer drug epirubicin to G-quadruplex [d-(TTAGGGT)]4 containing human telomeric DNA sequence induces thermal stabilization

Cited by 11 publications

References 85 publications

Ursolic Acid Enhances the Sensitivity of MCF-7 and MDA-MB-231 Cells to Epirubicin by Modulating the Autophagy Pathway

Ursolic Acid Enhances the Sensitivity of MCF-7 and MDA-MB-231 Cells to Epirubicin by Modulating the Autophagy Pathway

Transcription-associated topoisomerase activities control DNA-breaks production by G-quadruplex ligands

Interaction of 9-Methoxyluminarine with Different G-Quadruplex Topologies: Fluorescence and Circular Dichroism Studies

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