Effect of Palmatine Binding to MYC<italic style="font-style: italic"> </italic>G-quadruplex on Proliferation and Apoptosis of Colon Cancer Cells and Molecular Mechanism

Li-na WEN; Jian-hui LI; Han-ping SHI

doi:10.13422/j.cnki.syfjx.20211313

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Effect of Palmatine Binding to MYC G-quadruplex on Proliferation and Apoptosis of Colon Cancer Cells and Molecular Mechanism

更新时间：2021-10-14

- Effect of Palmatine Binding to MYC G-quadruplex on Proliferation and Apoptosis of Colon Cancer Cells and Molecular Mechanism
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 21, Pages: 98-104(2021)
- 作者机构：
  
  1.首都医科大学附属北京世纪坛医院，北京 100038
  2.中国科学院生物物理研究所，北京 100101
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20211313
  CLC： R285;R289;R22;R2-031;R33
- Received：20 May 2021，
  
  Published Online：14 September 2021，
  
  Published：05 November 2021
- 稿件说明：
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温丽娜,李建辉,石汉平.巴马汀结合MYCG-四链体干预结肠癌细胞增殖和凋亡的作用及分子机制[J].中国实验方剂学杂志,2021,27(21):98-104.

WEN Li-na,LI Jian-hui,SHI Han-ping.Effect of Palmatine Binding to MYCG-quadruplex on Proliferation and Apoptosis of Colon Cancer Cells and Molecular Mechanism[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(21):98-104.
温丽娜,李建辉,石汉平.巴马汀结合MYCG-四链体干预结肠癌细胞增殖和凋亡的作用及分子机制[J].中国实验方剂学杂志,2021,27(21):98-104. DOI： 10.13422/j.cnki.syfjx.20211313.

WEN Li-na,LI Jian-hui,SHI Han-ping.Effect of Palmatine Binding to MYCG-quadruplex on Proliferation and Apoptosis of Colon Cancer Cells and Molecular Mechanism[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(21):98-104. DOI： 10.13422/j.cnki.syfjx.20211313.

摘要

目的

探究巴马汀是否通过结合MYC原癌基因启动子区G-四链体干预结肠癌HCT116细胞的增殖及凋亡及其可能的分子机制。

方法

采用荧光光谱分析巴马汀与MYC基因G-四链体的结合能力，采用圆二色谱分析巴马汀对MYC基因G-四链体构型的影响，采用分子对接预测二者的结合模式，采用荧光显微镜分析巴马汀分子在HCT116细胞中的定位，采用实时荧光定量聚合酶链式反应分析巴马汀对MYC基因转录的影响，采用蛋白免疫印迹法检测巴马汀对MYC蛋白表达的影响，进一步采用噻唑蓝比色法分析巴马汀对HCT116细胞活力的影响，采用流式细胞术分析巴马汀对HCT116细胞凋亡的影响。

结果

荧光光谱及分子对接研究表明巴马汀可能以堆积方式与MYC基因G-四链体结合，圆二色谱分析表明马汀能够维持MYC基因G-四链体的平行构型，荧光成像分析表明巴马汀分布于细胞核中且能够与G-四链体结合。此外，巴马汀抑制了MYC基因转录及MYC蛋白表达，抑制了HCT116细胞的增殖并促进了细胞凋亡。

结论

巴马汀能够结合MYC基因G-四链体并抑制其基因转录，进而抑制MYC蛋白表达，这可能是巴马汀抑制结肠癌HCT116细胞增殖并促进其凋亡的分子机制之一。

Abstract

Objective

To explore whether palmatine interferes with the proliferation and apoptosis of colon cancer HCT116 cells by binding to G-quadruplex in the promoter region of MYC proto-oncogene and its possible molecular mechanism.

Method

Fluorescence spectrum was used to analyze the binding ability of palmatine to MYC G-quadruplex. Circular dichroism analysis was conducted to confirm the effect of palmatine on the configuration of MYC G-quadruplex， followed by the prediction of their binding mode based on molecular docking and the localization analysis of palmatine in HCT116 cells under a fluorescence microscope. The effects of palmatine on MYC gene transcription and MYC protein expression were determined by real-time fluorescence quantitative polymerase chain reaction and Western blot， respectively. The effects of palmatine on the viability and apoptosis of HCT116 cells were further assayed by thiazolyl blue tetrazolium bromide （MTT） assay and flow cytometry.

Result

As revealed by fluorescence spectrum and molecular docking analysis， palmatine might bind to G-quadruplex of MYC gene through stacking. Circular dichroism analysis showed that palmatine could maintain the parallel configuration of MYC

G-quadruplex. It was discovered in fluorescence imaging that palmatine was distributed in the nucleus and bond to G-quadruplex of MYC gene. In addition， palmatine inhibited MYC gene transcription， MYC protein expression， as well as the viability of HCT116 cells， and promoted the apoptosis of HCT116 cells.

Conclusion

Palmatine is able to bind to MYC G-quadruplex to further inhibit the expression of MYC gene and protein expression， which may be one of the molecular mechanisms of palmatine in suppressing the proliferation of colon cancer HCT116 cells and facilitating their apoptosis.

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references

KEUN N ， GIOVANNUCCI E . Global burden of colorectal cancer： emerging trends，risk factors and prevention strategies ［J］. Nat Rev Gastroenterol Hepatol ， 2019 ， 16 （ 12 ）： 713 - 732 .

PAESCHKE K ， BURKOVICS P . Mgs1 function at G-quadruplex structures during DNA replication ［J］. Curr Genet ， 2021 ， 67 （ 2 ）： 225 - 230 .

EDWARDS A D ， MARECKI J C ， BYRD A K ， et al . G-Quadruplex loops regulate PARP-1 enzymatic activation ［J］. Nucleic Acids Res ， 2021 ， 49 （ 1 ）： 416 - 431 .

VARSHNEY D ， SPIEGEL J ， ZYNER K ， et al . The regulation and functions of DNA and RNA G-quadruplexes ［J］. Nat Rev Mol Cell Biol ， 2020 ， 21 （ 8 ）： 459 - 474 .

LI C ， WU B ， CHEN S ， et al . Structural requirement of G-quadruplex/aptamer-combined DNA macromolecule serving as efficient drug carrier for cancer-targeted drug delivery ［J］. Eur J Pharm Biopharm ， 2021 ， 159 ： 221 - 227 .

张兆洲，李琦 . 癌毒传舍的中医病机初探［J］. 中华中医药杂志， 2018 ， 33 （ 11 ）： 4839 - 4843 .

戴小军，于彦威，刘延庆 . 毒邪理论治疗肿瘤源流及辨治要法［J］. 中华中医药杂志， 2020 ， 35 （ 10 ）： 5122 - 5127 .

戴逸飞，戴丽，隋峰，等 . 苦寒中药及其活性成分抗肿瘤作用及机制研究进展［J］. 中国实验方剂学杂志， 2017 ， 23 （ 4 ）： 215 - 221 .

LONG J ， SONG J ， ZHONG L ， et al . Palmatine： a review of its pharmacology，toxicity and pharmacokinetics ［J］. Biochimie ， 2019 ， 162 ： 176 - 184 .

WU J ， XIAO Q ， ZHANG N ， et al . Palmatine hydrochloride mediated photodynamic inactivation of breast cancer MCF-7 cells： effectiveness and mechanism of action ［J］. Photodiagnosis Photodyn Ther ， 2016 ， 15 ： 133 - 138 .

HAMBRIGHT H G ， BATTH I S ， XIE J ， et al . Palmatine inhibits growth and invasion in prostate cancer cell： potential role for rpS6/NFkappaB/FLIP ［J］. Mol Carcinog ， 2015 ， 54 （ 10 ）： 1227 - 1234 .

LIU X ， ZHANG Y ， WU S ， et al . Palmatine induces G 2 /M phase arrest and mitochondrial-associated pathway apoptosis in colon cancer cells by targeting AURKA ［J］. Biochem Pharmacol ， 2020 ， 175 ： 113933 .

李月华，曹爽 . 慢病毒介导的c-Myc启动子结合蛋白1过表达对结肠癌HCT116细胞增殖与凋亡的影响及其机制研宄［J］. 中华细胞与干细胞杂志：电子版， 2020 ， 10 （ 1 ）： 32 - 36 .

PANDA D ， SAHA P ， DAS T ， et al . Target guided synthesis using DNA nano-templates for selectively assembling a G-quadruplex binding c-MYC inhibitor ［J］. Nat Commun ， 2017 ， 8 ： 16103 .

WANG W ， HU S ， GU Y ， et al . Human MYC G-quadruplex： from discovery to a cancer therapeutic target ［J］. Biochim Biophys Acta Rev Cancer ， 2020 ， 1874 （ 2 ）： 188410 .

JI X ， SUN H ， ZHOU H ， et al . The interaction of telomeric DNA and C-MYC22 G-quadruplex with 11 natural alkaloids ［J］. Nucleic Acid Ther ， 2012 ， 22 （ 2 ）： 127 - 136 .

温丽娜，韩宗强 . 以KRAS启动子G-四链体DNA为靶点的小檗碱对人结肠癌细胞SW620的作用及机制［J］. 中国实验方剂学杂志， 2018 ， 24 （ 12 ）： 143 - 149 .

WANG M Q ， LIAO Y F ， ZHANG S H ， et al . Synthesis，G-quadruplex DNA binding and cytotoxic properties of naphthalimide substituted styryl dyes ［J］. Bioorg Med Chem ， 2020 ， 28 （ 5 ）： 115325 .

BALUAPURI A ， WOLF E ， EILERS M . Target gene-independent functions of MYC oncoproteins ［J］. Nat Rev Mol Cell Biol ， 2020 ， 21 （ 5 ）： 255 - 267 .

雷楠，熊思会，谭溧，等 . 野黄芩苷通过hedgehog信号通路抑制结肠肿瘤干细胞分化的研究［J］. 中国中药杂志， 2020 ， 45 （ 7 ）： 1676 - 1683 .

SABO A ， KRESS T R ， PELIZZOLA M ， et al . Selective transcriptional regulation by Myc in cellular growth control and lymphomagenesis ［J］. Nature ， 2014 ， 511 （ 7510 ）： 488 - 492 .

DAUCH D ， RUDALSKA R ， COSSA G ， et al . A MYC-aurora kinase A protein complex represents an actionable drug target in p53-altered liver cancer ［J］. Nat Med ， 2016 ， 22 （ 7 ）： 744 - 753 .

CHEN M C ， TIPPANA R ， DEMESHKINA N A ， et al . Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36 ［J］. Nature ， 2018 ， 558 （ 7710 ）： 465 - 469 .

HANSEL-HERTSCH R ， SPIEGEL J ， MARSICO G ， et al . Genome-wide mapping of endogenous G-quadruplex DNA structures by chromatin immunoprecipitation and high-throughput sequencing ［J］. Nat Protoc ， 2018 ， 13 （ 3 ）： 551 - 564 .

RIGO R ， PALUMBO M ， SISSI C . G-quadruplexes in human promoters： a challenge for therapeutic applications ［J］. Biochim Biophys Acta Gen Subj ， 2017 ， 1861 （ 5 PtB）： 1399 - 1413 .

HARCOURT E M ， KIETRYS A M ， KOOL E T . Chemical and structural effects of base modifications in messenger RNA ［J］. Nature ， 2017 ， 541 （ 7637 ）： 339 - 346 .

DUTTA D ， DEBNATH M ， MULLER D ， et al . Cell penetrating thiazole peptides inhibit c-MYC expression via site-specific targeting of c-MYC G-quadruplex ［J］. Nucleic Acids Res ， 2018 ， 46 （ 11 ）： 5355 - 5365 .

SENGUPTA P ， BANERIEE N ， ROYCHOWDHURY T ， et al . Site-specific amino acid substitution in dodecameric peptides determines the stability and unfolding of c-MYC quadruplex promoting apoptosis in cancer cells ［J］. Nucleic Acids Res ， 2018 ， 46 （ 19 ）： 9932 - 9950 .

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Effect of Palmatine Binding to MYC G-quadruplex on Proliferation and Apoptosis of Colon Cancer Cells and Molecular Mechanism

DOI：10.13422/j.cnki.syfjx.20211313

摘要

Abstract

关键词

Keywords

references