Bortezomib Potentiates the Effect of Roscovitine Via Dna Damage Induced Apoptosis in A549 Lung Cancer Cells

Gülşah Albayrak

doi:10.17776/csj.895309

EN

Bortezomib Potentiates the Effect of Roscovitine Via Dna Damage Induced Apoptosis in A549 Lung Cancer Cells

Abstract

The adoption of new treatment modalities remains crucial as lung cancer has one of the lowest survival rates, along with liver and pancreatic cancer. Bortezomib is a proteasome inhibitor that has higher anticancer effect in combination therapies. Therefore, the aim of this study is to investigate whether bortezomib could have additional anticancer effect when combined with cyclin-dependent kinase (CDK) inhibitor-roscovitine in vitro. Apoptosis related gene expression levels of p53, Noxa, Puma, Bcl-xL, Bak, Casp-3 and Casp-7 were measured by quantitative PCR (qPCR) upon treatment with 10-20μM roscovitine and in combination with 30nM bortezomib for 24 hours. Synergistic effect on apoptosis was also investigated at protein levels by analyzing p53, Cleaved Casp-3 and Cleaved Parp expressions. Induction of autophagy was determined by western blotting of B-catenin and LC3B I-II. Roscovitine combined bortezomib treatment induced apoptosis by upregulating p53 pathway and its downstream mediators. Bortezomib increased Parp and Caspase3 cleavage significantly at 24h. Bortezomib inhibited B-catenin and triggered autophagy induction at 24 and 48hours. As cancer cells evade programmed cell death, CDK inhibitors might be used to direct cancer cells into apoptosis. This study concludes that bortezomib potentiates the effect of roscovitine via DNA damage induced apoptosis in A549 lung cancer cells.

Keywords

References

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Details

Primary Language

English

Subjects

Structural Biology

Journal Section

Research Article

Authors

Gülşah Albayrak ^*
0000-0001-9106-5798
Türkiye

Publication Date

March 30, 2022

Submission Date

March 11, 2021

Acceptance Date

December 29, 2021

Published in Issue

Year 2022 Volume: 43 Number: 1

DOI

https://doi.org/10.17776/csj.895309

IZ

https://izlik.org/JA97DJ33XB

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RIS / Bibtex

APA

Albayrak, G. (2022). Bortezomib Potentiates the Effect of Roscovitine Via Dna Damage Induced Apoptosis in A549 Lung Cancer Cells. Cumhuriyet Science Journal, 43(1), 1-5. https://doi.org/10.17776/csj.895309

Öz

Bortezomib Potentiates the Effect of Roscovitine Via Dna Damage Induced Apoptosis in A549 Lung Cancer Cells

Abstract

Keywords

References

Details

Primary Language

Subjects

Journal Section

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Publication Date

Submission Date

Acceptance Date

Published in Issue

DOI

IZ

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