Selected ellipticine derivatives, known to target topoisomerase II, suppress the alternative lengthening of telomere (ALT) pathway in telomerase–negative cells

Zencir, Sevil; Hsieh, Meng-Hsun; Hsu, Joel-Sean; Ergün, Yavuz; Chou, Guan-Ling; Li, Tsai-Kun; Topçu, Zeki

doi:10.1007/s00432-020-03213-x

Cited by 4 publications

(7 citation statements)

References 32 publications

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“…Therefore, new ellipticine and olivacine derivatives should be studied in terms of direct interactions with nucleic acid, the affinity of these compounds for DNA and their effect on electrochemical reduction of DNA bases. It was also reported by Zencir et al that ellipticine and its derivatives can suppress telomere lengthening in cells, which can help to kill tumor cells [51].…”

Section: Discussionmentioning

confidence: 73%

Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II

Tylińska

Dobosz

Spychała

et al. 2021

IJMS

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Olivacine and ellipticine are model anticancer drugs acting as topoisomerase II inhibitors. Here, we present investigations performed on four olivacine derivatives in light of their antitumor activity. The aim of this study was to identify the best antitumor compound among the four tested olivacine derivatives. The study was performed using CCRF/CEM and MCF-7 cell lines. Comet assay, polarography, inhibition of topoisomerase II activity, histone acetylation, and molecular docking studies were performed. Each tested compound displayed interaction with DNA and topoisomerase II, but did not cause histone acetylation. Compound 2 (9-methoxy-5,6-dimethyl-1-({[1-hydroxy-2-(hydroxymethyl)butan-2-yl]amino}methyl)-6H-pyrido[4,3-b]carbazole) was found to be the best candidate as an anticancer drug because it had the highest affinity for topoisomerase II and caused the least genotoxic damage in cells.

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Section: Discussionmentioning

confidence: 73%

Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II

Tylińska

Dobosz

Spychała

et al. 2021

IJMS

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“…In recent years, many insightful discoveries have been made in elucidating the molecular mechanism of the ALT pathway. At the same time, a few novel and exciting molecular targets, including ATR, FANCM, and TOP2, have also been identified [ 25 , 27 , 188 , 200 , 201 ]. Recent small molecule screening suggests ATM inhibitor, KU60019; tyrosine kinase inhibitor, sunitinib; and HSP-90 inhibitor, 17-AAG are also promising [ 202 ].…”

Section: Discussionmentioning

confidence: 99%

“…In vivo and in vitro knockdown of TOP2A and TOP2B as well as TOP2 inhibitor, ICRF-193, treatment reduced APB formation, increased TIFs, shortened telomeres, and hindered proliferation of ALT+ OS cells and ALT+ lung fibroblasts [ 200 ]. Similarly, two recent ellipticine derivatives, Z1 and Z2, were found to decrease C-circle and APB formation via TOP2 inhibition [ 201 ]. However, unlike genistein and ICRF-193, their anti-proliferative effects were also observed in TEL+ HeLa cells.…”

Section: The Development Of Novel Therapiesmentioning

confidence: 99%

ALT Positivity in Human Cancers: Prevalence and Clinical Insights

MacKenzie

Watters

et al. 2021

Cancers

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Since it was first described over two decades ago, the Alternative Lengthening of Telomeres (ALT) pathway has been well accepted to hold clinical significance in cancer development, cancer diagnosis and cancer treatment. In this review, we first discuss how the activation of this pathway is determined. We then provide up-to-date statistics on the cancers ALT activity is detected. Additionally, we discussed the relationship between ALT positivity and prognosis as well as the pathogenetics of the ALT positive cancers. Finally, we evaluated the pre-clinical and clinical investigation of potential therapy for ALT cancers.Abstract: Many exciting advances in cancer-related telomere biology have been made in the past decade. Of these recent advances, great progress has also been made with respect to the Alternative Lengthening of Telomeres (ALT) pathway. Along with a better understanding of the molecular mechanism of this unique telomere maintenance pathway, many studies have also evaluated ALT activity in various cancer subtypes. We first briefly review and assess a variety of commonly used ALT biomarkers. Then, we provide both an update on ALT-positive (ALT+) tumor prevalence as well as a systematic clinical assessment of the presently studied ALT+ malignancies. Additionally, we discuss the pathogenetic alterations in ALT+ cancers, for example, the mutation status of ATRX and DAXX, and their correlations with the activation of the ALT pathway. Finally, we highlight important ALT+ clinical associations within each cancer subtype and subdivisions within, as well as their prognoses. We hope this alternative perspective will allow scientists, clinicians, and drug developers to have greater insight into the ALT cancers so that together, we may develop more efficacious treatments and improved management strategies to meet the urgent needs of cancer patients.

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“…This can explain the therapeutic failures and/or a resistance against telomerase inhibition-based anti-cancer therapy. Therefore, developing new therapeutics targeting proteins known to be involved in the latter pathway will be crucial for the targeting of ALT-specific cells (41).…”

Section: Telomerase Activity and Agingmentioning

confidence: 99%

Telomerase and telomeres in aging theory and chronographic aging theory (Review)

et al. 2020

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The current review focuses on the connection of telomerase and telomeres with aging. in this review, we describe the changes in telomerase and telomere length (Tel) during development, their role in carcinogenesis processes, and the consequences of reduced telomerase activity. More specifically, the connection of Tel in peripheral blood cells with the development of aging-associated diseases is discussed. The review provides systematic data on the role of telomerase in mitochondria, the biology of telomeres in stem cells, as well as the consequences of the forced expression of telomerase (telomerization) in human cells. additionally, it presents the effects of chronic stress exposure on telomerase activity, the effect of Tel on fertility, and the effect of nutraceutical supplements on Tel. Finally, a comparative review of the chronographic theory of aging, presented by olovnikov is provided based on currently available scientific research on telomere, telomerase activity, and the nature of aging by multicellular organisms. Contents 1. introduction 2. Telomeres and telomerase: The generation of aging theory 3. Telomerase activity and aging 4. chronographic theory of aging: neural chronograph 5. conclusions and future research directions

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Selected ellipticine derivatives, known to target topoisomerase II, suppress the alternative lengthening of telomere (ALT) pathway in telomerase–negative cells

Cited by 4 publications

References 32 publications

Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II

Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II

ALT Positivity in Human Cancers: Prevalence and Clinical Insights

Telomerase and telomeres in aging theory and chronographic aging theory (Review)

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