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Bortezomib synergizes with nocodazole in p53 mediated DNA damage response signalling in A549 lung cancer cells

Yıl 2021, Cilt: 25 Sayı: 3, 287 - 291, 27.06.2025

Gülşah Albayrak

Öz

The adoption of new treatment modalities is required to improve outcomes in lung cancer treatment as lung cancer has lowest survival rates, along with liver and pancreatic cancer. Bortezomib is a proteasome inhibitor that has higher anticancer effect in combination therapies. The aim of this study was to investigate whether bortezomib could have additional anticancer effect with antineoplastic tubulin binding agent -nocodazole in A549 lung cancer cells. Apoptosis related gene expression levels of Noxa, Bcl-xL, Casp3 and Casp7 were measured by real-time PCR after treatment with 30 nM bortezomib, 0.3 μg/ml nocodazole and with their combination for 24 hours. Synergistic effect on DNA damage response was investigated at protein levels by checking p53 and cleaved PARP expressions. Induction of apoptotis was determined at protein expression level by western blotting of XIAP, Bcl-X and Bim. It was found that nocodazole combined bortezomib treatment induced apoptosis via p53 mediated DNA damage response signalling. P53 and cleaved PARP protein expressions were increased significantly after combination treatment. Apoptosis related genes Noxa, Casp3 and Casp7 mRNA expressions were elevated significantly after combination treatment. This study concludes that bortezomib potentiates the effect of nocodazole via DNA damage induced apoptosis in A549 lung cancer cells.

Anahtar Kelimeler

Bortezomib Nocodazole DNA damage lung cancer

Kaynakça

  • [1] Barta JA, Powell CA, Wisnivesky JP. Global Epidemiology of Lung Cancer. Ann Glob Health. 2019; 85(1): 8. [CrossRef]
  • [2] Blandin Knight S, Crosbie PA, Balata H, Chudziak J, Hussell T, Dive C. Progress and prospects of early detection in lung cancer. Open Biol. 2017; 7(9): 170070. [CrossRef]
  • [3] Chen D, Frezza M, Schmitt S, Kanwar J, Dou QP. Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Targets. 2011; 11(3): 239-53. [CrossRef]
  • [4] Budenholzer L, Cheng CL, Li Y, Hochstrasser M. Proteasome Structure and Assembly. J Mol Biol. 2017; 429(22):3500-3524. [CrossRef]
  • [5] Bonvini P, Zorzi E, Basso G, Rosolen A. Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell lymphoma. Leukemia. 2007; 21(4): 838-42. [CrossRef]
  • [6] National Center for Biotechnology Information (2020). PubChem Compound Summary for CID 4122, Nocodazole. https://pubchem.ncbi.nlm.nih.gov/compound/Nocodazole (Accessed October 6, 2020).
  • [7] Lu Y, Chen J, Xiao M, Li W, Miller DD. An overview of tubulin inhibitors that interact with the colchicine binding site. Pharm Res. 2012; 29(11): 2943-71. [CrossRef]
  • [8] Kapoor P, Ramakrishnan V, Rajkumar SV. Bortezomib combination therapy in multiple myeloma. Semin Hematol. 2012; 49(3): 228-42. [CrossRef]
  • [9] Taromi S, Lewens F, Arsenic R, Sedding D, Sänger J, Kunze A, Möbs M, Benecke J, Freitag H, Christen F, Kaemmerer D, Lupp A, Heilmann M, Lammert H, Schneider CP, Richter K, Hummel M, Siegmund B, Burger M, Briest F, Grabowski P. Proteasome inhibitor bortezomib enhances the effect of standard chemotherapy in small cell lung cancer. Oncotarget. 2017; 8(57): 97061-97078. [CrossRef]
  • [10] Nocodazole product data sheet. https://www.cellsignal.co.uk/products/activators- inhibitors/nocodazole/2190?Ntk=Products&Ntt=2190 (Accessed October 6, 2020).
  • [11] Stevens M, Oltean S. Modulation of the Apoptosis Gene Bcl-x Function Through Alternative Splicing. Front Genet. 2019; 10: 804. [CrossRef]
  • [12] Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999; 6(2): 99-104. [CrossRef]
  • [13] 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 Res Notes. 2017; 10(1): 544.[CrossRef]
  • [14] Fridman JS, Lowe SW. Control of apoptosis by p53. Oncogene. 2003; 22(56): 9030-40. [CrossRef]
  • [15] Pitolli C, Wang Y, Candi E, Shi Y, Melino G, Amelio I. p53-Mediated Tumor Suppression: DNA-Damage Response and Alternative Mechanisms. Cancers (Basel). 2019; 11(12): 1983. [CrossRef]
  • [16] Chaitanya GV, Steven AJ, Babu PP. PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration. Cell Commun Signal. 2010; 8: 31. [CrossRef]
  • [17] Gobeil S, Boucher CC, Nadeau D, Poirier GG. Characterization of the necrotic cleavage of poly(ADP-ribose) polymerase (PARP-1): implication of lysosomal proteases. Cell Death Differ. 2001; 8(6): 588-94. [CrossRef]
  • [18] Beswick RW, Ambrose HE, Wagner SD. Nocodazole, a microtubule de-polymerising agent, induces apoptosis of chronic lymphocytic leukaemia cells associated with changes in Bcl-2 phosphorylation and expression. Leuk Res. 2006; 30(4): 427-36. [CrossRef]
  • [19] Yu Y, Jin H, Xu J, Gu J, Li X, Xie Q, Huang H, Li J, Tian Z, Jiang G, Chen C, He F, Wu XR, Huang C. XIAP overexpression promotes bladder cancer invasion in vitro and lung metastasis in vivo via enhancing nucleolin-mediated Rho-GDIβ mRNA stability. Int J Cancer. 2018; 142(10): 2040-2055. [CrossRef]
  • [20] Hussain AR, Siraj AK, Ahmed M, Bu R, Pratheeshkumar P, Alrashed AM, Qadri Z, Ajarim D, Al-Dayel F, Beg S, Al-Kuraya KS. XIAP over-expression is an independent poor prognostic marker in Middle Eastern breast cancer and can be targeted to induce efficient apoptosis. BMC Cancer. 2017; 17(1): 640.

Yıl 2021, Cilt: 25 Sayı: 3, 287 - 291, 27.06.2025

Gülşah Albayrak

Öz

Kaynakça

  • [1] Barta JA, Powell CA, Wisnivesky JP. Global Epidemiology of Lung Cancer. Ann Glob Health. 2019; 85(1): 8. [CrossRef]
  • [2] Blandin Knight S, Crosbie PA, Balata H, Chudziak J, Hussell T, Dive C. Progress and prospects of early detection in lung cancer. Open Biol. 2017; 7(9): 170070. [CrossRef]
  • [3] Chen D, Frezza M, Schmitt S, Kanwar J, Dou QP. Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Targets. 2011; 11(3): 239-53. [CrossRef]
  • [4] Budenholzer L, Cheng CL, Li Y, Hochstrasser M. Proteasome Structure and Assembly. J Mol Biol. 2017; 429(22):3500-3524. [CrossRef]
  • [5] Bonvini P, Zorzi E, Basso G, Rosolen A. Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell lymphoma. Leukemia. 2007; 21(4): 838-42. [CrossRef]
  • [6] National Center for Biotechnology Information (2020). PubChem Compound Summary for CID 4122, Nocodazole. https://pubchem.ncbi.nlm.nih.gov/compound/Nocodazole (Accessed October 6, 2020).
  • [7] Lu Y, Chen J, Xiao M, Li W, Miller DD. An overview of tubulin inhibitors that interact with the colchicine binding site. Pharm Res. 2012; 29(11): 2943-71. [CrossRef]
  • [8] Kapoor P, Ramakrishnan V, Rajkumar SV. Bortezomib combination therapy in multiple myeloma. Semin Hematol. 2012; 49(3): 228-42. [CrossRef]
  • [9] Taromi S, Lewens F, Arsenic R, Sedding D, Sänger J, Kunze A, Möbs M, Benecke J, Freitag H, Christen F, Kaemmerer D, Lupp A, Heilmann M, Lammert H, Schneider CP, Richter K, Hummel M, Siegmund B, Burger M, Briest F, Grabowski P. Proteasome inhibitor bortezomib enhances the effect of standard chemotherapy in small cell lung cancer. Oncotarget. 2017; 8(57): 97061-97078. [CrossRef]
  • [10] Nocodazole product data sheet. https://www.cellsignal.co.uk/products/activators- inhibitors/nocodazole/2190?Ntk=Products&Ntt=2190 (Accessed October 6, 2020).
  • [11] Stevens M, Oltean S. Modulation of the Apoptosis Gene Bcl-x Function Through Alternative Splicing. Front Genet. 2019; 10: 804. [CrossRef]
  • [12] Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999; 6(2): 99-104. [CrossRef]
  • [13] 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 Res Notes. 2017; 10(1): 544.[CrossRef]
  • [14] Fridman JS, Lowe SW. Control of apoptosis by p53. Oncogene. 2003; 22(56): 9030-40. [CrossRef]
  • [15] Pitolli C, Wang Y, Candi E, Shi Y, Melino G, Amelio I. p53-Mediated Tumor Suppression: DNA-Damage Response and Alternative Mechanisms. Cancers (Basel). 2019; 11(12): 1983. [CrossRef]
  • [16] Chaitanya GV, Steven AJ, Babu PP. PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration. Cell Commun Signal. 2010; 8: 31. [CrossRef]
  • [17] Gobeil S, Boucher CC, Nadeau D, Poirier GG. Characterization of the necrotic cleavage of poly(ADP-ribose) polymerase (PARP-1): implication of lysosomal proteases. Cell Death Differ. 2001; 8(6): 588-94. [CrossRef]
  • [18] Beswick RW, Ambrose HE, Wagner SD. Nocodazole, a microtubule de-polymerising agent, induces apoptosis of chronic lymphocytic leukaemia cells associated with changes in Bcl-2 phosphorylation and expression. Leuk Res. 2006; 30(4): 427-36. [CrossRef]
  • [19] Yu Y, Jin H, Xu J, Gu J, Li X, Xie Q, Huang H, Li J, Tian Z, Jiang G, Chen C, He F, Wu XR, Huang C. XIAP overexpression promotes bladder cancer invasion in vitro and lung metastasis in vivo via enhancing nucleolin-mediated Rho-GDIβ mRNA stability. Int J Cancer. 2018; 142(10): 2040-2055. [CrossRef]
  • [20] Hussain AR, Siraj AK, Ahmed M, Bu R, Pratheeshkumar P, Alrashed AM, Qadri Z, Ajarim D, Al-Dayel F, Beg S, Al-Kuraya KS. XIAP over-expression is an independent poor prognostic marker in Middle Eastern breast cancer and can be targeted to induce efficient apoptosis. BMC Cancer. 2017; 17(1): 640.
Toplam 20 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri (Diğer)
Bölüm Articles
Yazarlar

Gülşah Albayrak

Yayımlanma Tarihi 27 Haziran 2025
Yayımlandığı Sayı Yıl 2021 Cilt: 25 Sayı: 3

Kaynak Göster

APA Albayrak, G. (2025). Bortezomib synergizes with nocodazole in p53 mediated DNA damage response signalling in A549 lung cancer cells. Journal of Research in Pharmacy, 25(3), 287-291.
AMA Albayrak G. Bortezomib synergizes with nocodazole in p53 mediated DNA damage response signalling in A549 lung cancer cells. J. Res. Pharm. Haziran 2025;25(3):287-291.
Chicago Albayrak, Gülşah. “Bortezomib Synergizes With Nocodazole in p53 Mediated DNA Damage Response Signalling in A549 Lung Cancer Cells”. Journal of Research in Pharmacy 25, sy. 3 (Haziran 2025): 287-91.
EndNote Albayrak G (01 Haziran 2025) Bortezomib synergizes with nocodazole in p53 mediated DNA damage response signalling in A549 lung cancer cells. Journal of Research in Pharmacy 25 3 287–291.
IEEE G. Albayrak, “Bortezomib synergizes with nocodazole in p53 mediated DNA damage response signalling in A549 lung cancer cells”, J. Res. Pharm., c. 25, sy. 3, ss. 287–291, 2025.
ISNAD Albayrak, Gülşah. “Bortezomib Synergizes With Nocodazole in p53 Mediated DNA Damage Response Signalling in A549 Lung Cancer Cells”. Journal of Research in Pharmacy 25/3 (Haziran 2025), 287-291.
JAMA Albayrak G. Bortezomib synergizes with nocodazole in p53 mediated DNA damage response signalling in A549 lung cancer cells. J. Res. Pharm. 2025;25:287–291.
MLA Albayrak, Gülşah. “Bortezomib Synergizes With Nocodazole in p53 Mediated DNA Damage Response Signalling in A549 Lung Cancer Cells”. Journal of Research in Pharmacy, c. 25, sy. 3, 2025, ss. 287-91.
Vancouver Albayrak G. Bortezomib synergizes with nocodazole in p53 mediated DNA damage response signalling in A549 lung cancer cells. J. Res. Pharm. 2025;25(3):287-91.