|Table of Contents|

Tetramethylpyrazine regulates DNA damage repair in breast cancer cells through RAD52

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 01
Page:
47-52
Research Field:
Publishing date:

Info

Title:
Tetramethylpyrazine regulates DNA damage repair in breast cancer cells through RAD52
Author(s):
HUANG Puwan1; 2; CHEN Silong2; TANG Xijun1; WU Xiangfeng1; LI Liping2
1.Department of Laboratory,Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine,Guangdong Zhuhai 519000,China;2.Department of Biochemistry,Guangdong Medical University,Guangdong Dongguan 523808,China.
Keywords:
DNA double strand break repair; tetramethylpyrazine; breast cancer cells
PACS:
R737.9
DOI:
10.3969/j.issn.1672-4992.2024.01.008
Abstract:
Objective:To explore the relationship between TMP-induced cell proliferation,cell cycle and the expression of regulatory proteins in breast cancer BT474 cells and DNA double-strand break repair pathway.Methods:The proliferation inhibition of TMP on breast cancer cell line BT474 was detected by CCK8 method,the effect of TMP on cell cycle was determined by flow cytometry.The effect of TMP on DSBs accumulation after injury was analyzed by single cell gel electrophoresis.The effect of TMP on the activity of repair pathway was detected by Isce-I endonuclease system,and the expression of chromosome binding proteins related to DSBs repair pathway was detected by Western blotting.Results:TMP inhibited the proliferation of BT474 cells in a concentration-dependent manner,arrested cells in G1 phase,and significantly decreased the content of DNA in tailing cells induced by Zeocin.TMP significantly increased the recruitment of RAD52,ERCC1,XRCC4 and DNA Lig IV proteins by BT474 cells,decreased the recruitment of KU80 proteins,and promoted the repair activity of SSA and NHEJ pathway.Conclusion:TMP can inhibit the proliferation of BT474 cells by blocking the G1 phase,and TMP can enhance the recruitment of key chromosome binding proteins in each pathway and promote the activity of SSA and NHEJ repair pathway to reduce DNA damage（P＜0.05）.

References:

[1]DOIG KD,FELLOWES AP,FOX SB.Homologous recombination repair deficiency:An overview for pathologists［J］.Modern Pathology,2023,36(3):100049.
[2] COLLINS A,MOLLER P,GAJSKI G,et al.Measuring DNA modifications with the comet assay:a compendium of protocols［J］.Nature Protocols,2023,18(3):929-989.
[3] BARSZCZEWSKA PG,DRZEWIECKA M,CZARNY P,et al.Polθ inhibition:An anticancer therapy for HR-deficient tumours［J］.International Journal of Molecular Sciences,2022,24(1):319.
[4] CHRISTIE SM,FIJEN C,ROTHENBERG E.V(D)J recombination:Recent insights in formation of the recombinase complex and recruitment of DNA repair machinery［J］.Frontiers in Cell and Developmental Biology,2022,10:886718.
[5] DE GROOTD,SPANJAARD A,HOGENBIRK MA,et al.Chromosomal rearrangements and chromothripsis:The alternative end generation model［J］.International Journal of Molecular Sciences,2023,24(1):794.
[6] HUANG J,COOK DE.The contribution of DNA repair pathways to genome editing and evolution in filamentous pathogens［J］.FEMS Microbiology Reviews,2022,46(6):fuac035.
[7] SHI X,ZHAO S,CHEN S,et al.Tetramethylpyrazine in Chinese baijiu:Presence,analysis,formation,and regulation［J］.Frontiers in Nutrition,2022,9:1004435.
[8] IANG R,XU J,ZHANG Y,et al.Ligustrazine alleviate acute lung injury through suppressing pyroptosis and apoptosis of alveolar macrophages［J］.Front Pharmacol,2021,12:680512.
[9] LI X,LIN Z,WANG P,et al.Tetramethylpyrazine-rhein derivative inhibits the migration of canine inflammatory mammary carcinoma cells by mitochondrial damage-mediated apoptosis and cadherins downregulation［J］.Biomed Pharmacother,2023,162:114731.
[10] LIN J,WANG Q,ZHOU S,et al.Tetramethylpyrazine:A review on its mechanisms and functions［J］.Biomed Pharmacother,2022,150:113005.
[11] ZHENG H,WANG S,ZHOU P,et al.Effects of Ligustrazine on DNA damage and apoptosis induced by irradiation［J］.Environmental Toxicology and Pharmacology,2013,36(3):1197-11206.
[12] TODOROVA T,MITEVA D,CHANKOVA S.DNA susceptibility of Saccharomyces cerevisiae to Zeocin depends on the growth phase［J］.International Microbiology,2019,22(4):419-4428.
[13] GUNN A,STARK JM.I-SceI-based assays to examine distinct repair outcomes of mammalian chromosomal double strand breaks［J］.Methods in Molecular Biology,2012,920:379-391.
[14] ZHANG FL,YANG SY,LIAO L,et al.Dynamic SUMOylation of MORC2 orchestrates chromatin remodelling and DNA repair in response to DNA damage and drives chemoresistance in breast cancer［J］.Theranostics,2023,13(3):973-990.
[15] LORD CJ,ASHWORTH A.The DNA damage response and cancer therapy［J］.Nature,2012,481(7381):287-294.
[16] YU Y,YU J,GE S,et al.Novel insight into metabolic reprogrammming in cancer radioresistance:A promising therapeutic target in radiotherapy［J］.International Journal of Biological Sciences,2023,19(3):811-828.
[17] LIPTAY M,BARBOSA JS,ROTTENBERG S.Replication fork remodeling and therapy escape in DNA damage response-deficient cancers［J］.Frontiers in Oncology,2020,10:670.
[18] LUO J,LI Y,ZHANG T,et al.Extrachromosomal circular DNA in cancer drug resistance and its potential clinical implications［J］.Frontiers in Oncology,2022,12:1092705.
[19] JACKSON SP,BARTEK J.The DNA-damage response in human biology and disease［J］.Nature,2009,461(7267):1071-1078.
[20] XU Y,XU D.Repair pathway choice for double-strand breaks［J］.Essays in Biochemistry,2020,64(5):765-777.
[21] HER J,BUNTING SF.How cells ensure correct repair of DNA double-strand breaks［J］.The Journal of Biological Chemistry,2018,293(27):10502-10511.

Memo

Memo:
广东省中医药局科研项目（编号：2018124）；广东省珠海市医学科研项目（编号：ZH3310200028PJL）
Last Update: 2023-11-30