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Year 2022, , 1 - 5, 30.03.2022

Gülşah Albayrak

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

Abstract

References

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  • [2] de Groot P.M., Wu C.C., Carter B.W., Munden R.F., The epidemiology of lung cancer, Translational Lung Cancer Research, 7(3) (2018) 220.
  • [3] Luo Y.H., Luo L., Wampfler J.A., Wang Y., Liu D., Chen Y.M., Adjei A.A., Midthun D.E., Yang P., 5-year overall survival in patients with lung cancer eligible or ineligible for screening according to US Preventive Services Task Force criteria: a prospective, observational cohort study, The Lancet Oncology, 20(8) (2019) 1098-1108.
  • [4] Cicenas J., Kalyan K., Sorokinas A., Stankunas E., Levy J., Meskinyte I., Stankevicius V., Kaupinis A., Valius M., Roscovitine in cancer and other diseasesi, Annals of Translational Medicine, 3(10) (2015).
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  • [11] Ping Dou Q., A Zonder J., Overview of proteasome inhibitor-based anti-cancer therapies: perspective on bortezomib and second generation proteasome inhibitors versus future generation inhibitors of ubiquitin-proteasome system, Current Cancer Drug Targets, 14(6) (2014) 517-536.
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  • [14] Zhang T., Jiang T., Zhang F., Li C., Zhou Y.A., Zhu Y.F., Li X.F., Involvement of p21Waf1/Cip1 cleavage during roscovitine-induced apoptosis in non-small cell lung cancer cells, Oncology reports, 23(1) (2010) 239-245.
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  • [23] Herceg Z., Wang Z.Q., Failure of poly (ADP-ribose) polymerase cleavage by caspases leads to induction of necrosis and enhanced apoptosis, Molecular and Cellular Biology, 19(7) (1999) 5124-5133.

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

Year 2022, , 1 - 5, 30.03.2022

Gülşah Albayrak

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

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

CDK inhibitor Lung cancer Bortezomib Apoptosis Roscovitine

References

  • [1] Barta J.A., Powell C.A., Wisnivesky J.P., Global epidemiology of lung cancer, Annals of Global Health, 85(1) (2019).
  • [2] de Groot P.M., Wu C.C., Carter B.W., Munden R.F., The epidemiology of lung cancer, Translational Lung Cancer Research, 7(3) (2018) 220.
  • [3] Luo Y.H., Luo L., Wampfler J.A., Wang Y., Liu D., Chen Y.M., Adjei A.A., Midthun D.E., Yang P., 5-year overall survival in patients with lung cancer eligible or ineligible for screening according to US Preventive Services Task Force criteria: a prospective, observational cohort study, The Lancet Oncology, 20(8) (2019) 1098-1108.
  • [4] Cicenas J., Kalyan K., Sorokinas A., Stankunas E., Levy J., Meskinyte I., Stankevicius V., Kaupinis A., Valius M., Roscovitine in cancer and other diseasesi, Annals of Translational Medicine, 3(10) (2015).
  • [5] Langlois F., Chu J., Fleseriu M., Pituitary-directed therapies for Cushing’s disease, Frontiers in Endocrinology, 9 (2018) 164.
  • [6] Bettayeb K., Oumata N., Echalier A., Ferandin Y., Endicott J.A., Galons H., Meijer L., CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases, Oncogene, 27(44) (2008) 5797-5807.
  • [7] Chen D., Frezza M., Schmitt S., Kanwar J., P Dou Q., Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives, Current Cancer Drug Targets, 11(3) (2011) 239-253.
  • [8] Thibaudeau T.A., Smith D.M., A practical review of proteasome pharmacology, Pharmacological Reviews, 71(2) (2019) 170-197.
  • [9] Shang F., Taylor A., Ubiquitin–proteasome pathway and cellular responses to oxidative stress, Free Radical Biology and Medicine, 51(1) (2011) 5-16.
  • [10] Soave C.L., Guerin T., Liu J., Dou Q.P., Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing, Cancer and Metastasis Reviews, 36(4) (2017) 717-736.
  • [11] Ping Dou Q., A Zonder J., Overview of proteasome inhibitor-based anti-cancer therapies: perspective on bortezomib and second generation proteasome inhibitors versus future generation inhibitors of ubiquitin-proteasome system, Current Cancer Drug Targets, 14(6) (2014) 517-536.
  • [12] Kapoor P., Ramakrishnan V., Rajkumar S.V., Bortezomib combination therapy in multiple myeloma, In Seminars in Hematology, 49(3) (2012) 228-242.
  • [13] Taromi S., Lewens F., Arsenic R., Sedding D., Sänger J., Kunze A., Moebs M., Benecke J., Freitag H., Christen F., Kaemmerer D., Proteasome inhibitor bortezomib enhances the effect of standard chemotherapy in small cell lung cancer, Oncotarget 8(57) (2017) 97061.
  • [14] Zhang T., Jiang T., Zhang F., Li C., Zhou Y.A., Zhu Y.F., Li X.F., Involvement of p21Waf1/Cip1 cleavage during roscovitine-induced apoptosis in non-small cell lung cancer cells, Oncology reports, 23(1) (2010) 239-245.
  • [15] Bertoli C., Skotheim J.M., De Bruin R.A., Control of cell cycle transcription during G1 and S phases, Nature Reviews Molecular Cell Biology, 14(8) (2013) 518-528.
  • [16] Law M.E., Corsino P.E., Narayan S., Law B.K., Cyclin-dependent kinase inhibitors as anticancer therapeutics, Molecular Pharmacology, 88(5) (2015) 846-852.
  • [17] Bhullar K.S., Lagarón N.O., McGowan E.M., Parmar I., Jha A., Hubbard B.P., Rupasinghe H.V., Kinase-targeted cancer therapies: progress, challenges and future directions, Molecular Cancer, 17(1) (2018) 1-20.
  • [18] Sooman L., Gullbo J., Bergqvist M., Bergström S., Lennartsson J., Ekman S., Synergistic effects of combining proteasome inhibitors with chemotherapeutic drugs in lung cancer cells, BMC Research Notes, 10(1) (2017) 1-9.
  • [19] Pandey V., Ranjan N., Narne P., Babu P.P., Roscovitine effectively enhances antitumor activity of temozolomide in vitro and in vivo mediated by increased autophagy and Caspase-3 dependent apoptosis, Scientific Reports, 9(1) (2019) 1-13.
  • [20] Fridman J.S., Lowe S.W., Control of apoptosis by p53, Oncogene, 22(56) (2003) 9030-9040.
  • [21] Stevens M., Oltean S., Modulation of the apoptosis gene Bcl-x function through alternative splicing, Frontiers in Genetics, 10 (2019) 804.
  • [22] Porter A.G., Jänicke R.U., Emerging roles of caspase-3 in apoptosis, Cell Death & Differentiation, 6(2) (1999) 99-104.
  • [23] Herceg Z., Wang Z.Q., Failure of poly (ADP-ribose) polymerase cleavage by caspases leads to induction of necrosis and enhanced apoptosis, Molecular and Cellular Biology, 19(7) (1999) 5124-5133.
There are 23 citations in total.

Details

Primary Language English
Subjects Structural Biology
Journal Section Natural Sciences
Authors

Gülşah Albayrak 0000-0001-9106-5798

Publication Date March 30, 2022
Submission Date March 11, 2021
Acceptance Date December 29, 2021
Published in Issue Year 2022

Cite

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