CoChat
Sign Up
Cited by 4PARP inhibition in cancer therapyAngiogenesis and VEGF in CancerDNA Repair Mechanisms

The DOI matches its Crossref record.

Novel PARP Inhibitor DDPF-20 Induces DNA Damage and Inhibits Angiogenesis through the PI3K/Akt/VEGF Pathway

Wang, Tian, Zhang, Dong, Guo, Chuanlong, Zhu, Wenyong·2022·Anti-Cancer Agents in Medicinal Chemistry
DOI 10.2174/1871520622666220221115007
Open this paper in CoChat — free account

Abstract

Background: Poly (ADP-ribose) polymerase (PARP) plays a key role in DNA damage repair. A novel compound (E)-N'-(2,3-dibromo-4,5-dihydroxyphenyl)-N-(phenylcarbamothioyl)formimidamide (DDPF-20) with excellent PARP inhibitory activity was synthesized. Objective: In this study, we aimed to clarify the mechanism of the novel PARP inhibitor DDPF-20 against lung cancer by inducing DNA damage and inhibiting angiogenesis. Method: The cytotoxic effect of DDPF-20 on the A549 cell line was determined with an MTT assay. Cell cycle and apoptosis were determined by a flow cytometer. Moreover, the γH2AX foci were detected by immunofluorescence. Capillary-like tube formation assay and chick chorioallantoic membrane (CAM) assay were used to detect the angiogenesis inhibitory effect of DDPF-20. The expressions of related proteins were detected by western blot. The anticancer activity of DDPF-20 in vivo was also detected. Results: With an IC50 value of 52.42 ± 15.13 nM, DDPF-20 inhibited the proliferation, induced G2/M cycle arrest, and induced apoptosis of human lung cancer A549 cells. Further research showed that DDPF-20 induced DNA doublestrand breaks (DSBs). Interestingly, DDPF-20 inhibited the tube formation of HUVEC cells, as well as inhibited the neovascularization of CAM, proving the angiogenesis inhibitory ability of DDPF-20. Mechanism studies proved that DDPF-20 inhibited the PI3K/Akt/VEGF signaling pathway. In an in vivo study, DDPF-20 inhibited tumor growth of an A549 xenograft. Analysis of the molecular mechanism underlying this effect revealed that the PI3K/Akt/VEGF pathway was involved in DDPF-20-induced cell death and inhibited angiogenesis in vivo. Conclusion: This study suggested that the novel PARP inhibitor DDPF-20 may have therapeutic potential in treating lung cancer.

Overview

Integrity signals

Registry

Crossref · 10.2174/1871520622666220221115007

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 38

  1. Siegel R.L.; Miller K.D.; Jemal A.; Cancer statistics, 2018. CA Cancer J Clin 2018,68(1),7-30 · DOI
  2. Rami-Porta R.; Asamura H.; Travis W.D.; Rusch V.W.; Lung cancer - major changes in the American joint committee on cancer eighth edition cancer staging manual. CA Cancer J Clin 2017,67(2),138-155 · DOI
  3. Reck M.; Heigener D.F.; Mok T.; Soria J-C.; Rabe K.F.; Management of non-small-cell lung cancer: Recent developments. Lancet 2013,382(9893),709-719 · DOI
  4. Lord C.J.; Ashworth A.; The DNA damage response and cancer therapy. Nature 2012,481(7381),287-294 · DOI · Paper page
  5. Oza A.M.; Cibula D.; Benzaquen A.O.; Poole C.; Mathijssen R.H.J.; Sonke G.S.; Colombo N.; Špaček, J.; Vuylsteke, P.; Hirte, H.; Mahner, S.; Plante, M.; Schmalfeldt, B.; Mackay, H.; Rowbottom, J.; Lowe, E.S.; Dougherty, B.; Barrett, J.C.; Friedlander, M. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: A randomised phase 2 trial. Lancet Oncol 2015,16(1),87-97 · DOI
  6. Lok B.H.; Gardner E.E.; Schneeberger V.E.; Ni A.; Desmeules P.; Rekhtman N.; de Stanchina E.; Teicher B.A.; Riaz N.; Powell S.N.; Poirier J.T.; Rudin C.M.; PARP inhibitor activity correlates with SLFN11 expression and demonstrates synergy with temozolomide in small cell lung cancer. Clin Cancer Res 2017,23(2),523-535 · DOI
  7. Jiang Y.; Dai H.; Li Y.; Yin J.; Guo S.; Lin S.Y.; McGrail D.J.; PARP inhibitors synergize with gemcitabine by potentiating DNA damage in non-small-cell lung cancer. Int J Cancer 2019,144(5),1092-1103 · DOI
  8. Li L.; Zhu T.; Gao Y.F.; Zheng W.; Wang C.J.; Xiao L.; Huang M.S.; Yin J.Y.; Zhou H.H.; Liu Z.Q.; Targeting DNA damage response in the radio(Chemo)therapy of non-small cell lung cancer. Int J Mol Sci 2016,17(6),E839 · DOI
  9. Cho W.C.; Jour G.; Aung P.P.; Role of angiogenesis in melanoma progression: Update on key angiogenic mechanisms and other associated components. Semin Cancer Biol 2019,59,175-186 · DOI
  10. Carmeliet P.; Jain R.K.; Molecular mechanisms and clinical applications of angiogenesis. Nature 2011,473(7347),298-307 · DOI · Paper page
  11. Tian W.; Cao C.; Shu L.; Wu F.; Anti-Angiogenic Therapy in the treatment of non-small cell lung cancer. OncoTargets Ther 2020,13,12113-12129 · DOI
  12. Hassan M.; Watari H.; AbuAlmaaty A.; Ohba Y.; Sakuragi N.; Apoptosis and molecular targeting therapy in cancer. BioMed Res Int 2014,2014,150845 · DOI
  13. Burz C.; Berindan-Neagoe I.; Balacescu O.; Irimie A.; Apoptosis in cancer: Key molecular signaling pathways and therapy targets. Acta Oncol 2009,48(6),811-821 · DOI
  14. Anzell A.R.; Maizy R.; Przyklenk K.; Sanderson T.H.; Mitochondrial quality control and disease: Insights into ischemia-reperfusion injury. Mol Neurobiol 2018,55(3),2547-2564 · DOI
  15. Guo C.; Zhang F.; Wu X.; Yu X.; Wu X.; Shi D.; Wang L.; BTH-8, a novel poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor, causes DNA double-strand breaks and exhibits anticancer activities in vitro and in vivo. Int J Biol Macromol 2020,150,238-245 · DOI
  16. Jeyamohan S.; Moorthy R.K.; Kannan M.K.; Arockiam A.J.V.; Parthenolide induces apoptosis and autophagy through the suppression of PI3K/Akt signaling pathway in cervical cancer. Biotechnol Lett 2016,38(8),1251-1260 · DOI
  17. Guo C.L.; Wang L.J.; Zhao Y.; Liu H.; Li X.Q.; Jiang B.; Luo J.; Guo S.J.; Wu N.; Shi D.Y.; A novel bromophenol derivative BOS-102 induces cell cycle arrest and apoptosis in human A549 lung cancer cells via ROS-mediated PI3K/Akt and the MAPK signaling pathway. Mar Drugs 2018,16(2),E43 · DOI
  18. Jiang B.; Luo J.; Guo S.; Wang L.; Discovery of 5-(3-bromo-2-(2,3-dibromo-4,5-dimethoxybenzyl)-4,5-dimethoxybenzylidene)thiazolidine-2,4-dione as a novel potent protein tyrosine phosphatase 1B inhibitor with antidiabetic properties. Bioorg Chem 2021,108,104648 · DOI
  19. Zhang L.; Luo J.; Li X.; Guo S.; Shi D.; 16S rRNA sequencing and metagenomics study of gut microbiota: Implications of BDB on Type 2 diabetes mellitus. Mar Drugs 2020,18(9),E469 · DOI
  20. Luo J.; Zhang R.; Wang X.; Hou Z.; Guo S.; Jiang B.; Binding properties of marine bromophenols with human protein tyrosine phosphatase 1B: Molecular docking, surface plasmon resonance and cellular insulin resistance study. Int J Biol Macromol 2020,163,200-208 · DOI
  21. Guo C.; Wang L.; Li X.; Wang S.; Yu X.; Xu K.; Zhao Y.; Luo J.; Li X.; Jiang B.; Shi D.; Discovery of novel bromophenol - thiosemicarbazone hybrids as potent selectve inhibitors of poly(ADP-ribose) polymerase-1 (PARP1) for use in cancer. J Med Chem 2019,62(6),3051-3067 · DOI
  22. Wang L.; Zhang S.; Yu X.; Guo C.; Novel Poly(ADP-ribose) Polymerase-1 inhibitor DDHCB inhibits proliferation of BRCA mutant breast cancer cell in vitro and in vivo through a synthetic lethal mechanism. Chem Res Toxicol 2020,33(7),1874-1881 · DOI
  23. Yin H.; Guo C.; Wang Y.; Liu D.; Lv Y.; Lv F.; Lu Z.; Fengycin inhibits the growth of the human lung cancer cell line 95D through reactive oxygen species produc-tion and mitochondria-dependent apoptosis. Anticancer Drugs 2013,24(6),587-598 · DOI
  24. Guo C.; Wang L.; Jiang B.; Shi D.; Bromophenol curcumin analog BCA-5 exerts an antiangiogenic effect through the HIF-1α/VEGF/Akt signaling pathway in human umbilical vein endothelial cells. Anticancer Drugs 2018,29(10),965-974 · DOI
  25. Ray Chaudhuri A.; Nussenzweig A.; The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat Rev Mol Cell Biol 2017,18(10),610-621 · DOI · Paper page
  26. Malyuchenko N.V.; Kotova E.Y.; Kulaeva O.I.; Kirpichnikov M.P.; Studitskiy V.M.; PARP1 Inhibitors: Antitumor drug design. Acta Nat (Engl Ed) 2015,7(3),27-37 · DOI
  27. Chen X.; Huan X.; Liu Q.; Wang Y.; He Q.; Tan C.; Chen Y.; Ding J.; Xu Y.; Miao Z.; Yang C.; Design and synthesis of 2-(4,5,6,7-tetrahydrothienopyridin-2-yl)-benzoimidazole carboxamides as novel orally efficacious Poly(ADP-ribose)polymerase (PARP) inhibitors. Eur J Med Chem 2018,145,389-403 · DOI
  28. Wang L-J.; Guo C-L.; Li X-Q.; Wang S-Y.; Jiang B.; Zhao Y.; Luo J.; Xu K.; Liu H.; Guo S-J.; Wu N.; Shi D-Y.; Discovery of novel bromophenol hybrids as potential anticancer agents through the Ros-mediated apoptotic pathway: Design, synthesis and biological evaluation. Mar Drugs 2017,15(11),343 · DOI
  29. Liu H.; Guo C.; Guo S.; Wang L.; Shi D.; Design and synthesis of a fluorescent probe with a large stokes shift for detecting thiophenols and its application in water samples and living cells. Molecules 2019,24(2),E375 · DOI
  30. Huang X.; Zhou W.; Zhang Y.; Liu Y.; High expression of PTGR1 promotes NSCLC cell growth via positive regulation of cyclin-dependent protein kinase complex. BioMed Res Int 2016,2016,5230642 · DOI
  31. Rajput S.; Kumar B.N.; Dey K.K.; Pal I.; Parekh A.; Mandal M.; Molecular targeting of Akt by thymoquinone promotes G(1) arrest through translation inhibition of cyclin D1 and induces apoptosis in breast cancer cells. Life Sci 2013,93(21),783-790 · DOI
  32. Kaminskyy V.O.; Piskunova T.; Zborovskaya I.B.; Tchevkina E.M.; Zhivotovsky B.; Suppression of basal autophagy reduces lung cancer cell proliferation and enhanc-es caspase-dependent and -independent apoptosis by stimulating ROS formation. Autophagy 2012,8(7),1032-1044 · DOI
  33. Lee K.C.; Chen Y.L.; Lin P.Y.; Chuang W.L.; Ursolic acid-induced apoptosis via regulation of the PI3K/Akt and MAPK signaling pathways in Huh-7 cells. Molecules 2018,23(8),E2016 · DOI
  34. Zhao X.; Ren X.; Zhu R.; Luo Z.; Ren B.; Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria-mediated apoptosis in zebrafish embryos. Aquat Toxicol 2016,180,56-70 · DOI
  35. Chuang W.L.; Lin P.Y.; Lin H.C.; Chen Y.L.; The apoptotic effect of ursolic acid on SK-Hep-1 cells is regulated by the PI3K/Akt, p38 and JNK MAPK signaling path-ways. Molecules 2016,21(4),460 · DOI
  36. Dai J.; Peng L.; Fan K.; Wang H.; Wei R.; Ji G.; Cai J.; Lu B.; Li B.; Zhang D.; Kang Y.; Tan M.; Qian W.; Guo Y.; Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells. Oncogene 2009,28(38),3412-3422 · DOI
  37. Alevizakos M.; Kaltsas S.; Syrigos K.N.; The VEGF pathway in lung cancer. Cancer Chemother Pharmacol 2013,72(6),1169-1181 · DOI
  38. Di Domenico M.; Ricciardi C.; Fusco A.; Pierantoni G.M.; Anti-VEGF therapy in breast and lung mouse models of cancers. J Biomed Biotechnol 2011,2011,947928 · DOI

Cited by

Sorted by citations

See all 4

Metadata

Authors
Wang, T., Zhang, D., Guo, C., & Zhu, W.
Affiliations
  • Shandong University (CN)
  • Department of Thoracic Surgery, Pingdu People\'s Hospital, Pingdu, Shandong, 266700, China
  • Qingdao University of Science and Technology (CN)
Corresponding author
Zhu, Wenyong
ORCID
Venue
Anti-Cancer Agents in Medicinal Chemistry
Publisher
Bentham Science Publishers Ltd.
Published
2022-08
Volume
22
Issue
13
Pages
2468-2476
ISSN
  • 1568-0118 (ISSN-L)
  • 1871-5206
DOI
10.2174/1871520622666220221115007
OpenAlex
W4212991391
Cited by
4
References
0
Citations by year
2026: 1 · 2024: 1 · 2023: 2
FWCI
0.32
Type
journal article
Language
en
Open access
closed
Locations
  • Anti-Cancer Agents in Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
PARP inhibitors, lung cancer, DNA damage, DNA double-strand breaks, angiogenesis inhibition, apoptosis, G2/M cell cycle arrest, γH2AX foci, tumor xenografts, anticancer activity
MeSH terms
Poly(ADP-ribose) Polymerase Inhibitors, Antineoplastic Agents, DNA Damage, Humans, Lung Neoplasms, Neovascularization, Pathologic, Poly(ADP-ribose) Polymerases, Apoptosis, Phosphatidylinositol 3-Kinases, Vascular Endothelial Growth Factor A, Cell Line, Tumor, Cell Proliferation, Proto-Oncogene Proteins c-akt

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review