Login Register Cart 0
Research Article

一种新的组蛋白去乙酰化酶抑制剂YF343与CQ联合抑制自噬有助于增加三阴性乳腺癌细胞凋亡

卷 30, 期 40, 2023

发表于: 08 March, 2023

页: [4605 - 4621] 页: 17

弟呕挨: 10.2174/0929867330666230120152815

价格: $65

摘要

背景：靶向肿瘤表观遗传事件的化合物可能构成抗癌治疗的重要策略。组蛋白去乙酰化酶抑制剂(Histone deacetylase inhibitors, HDACis)已成为抗癌药物开发的潜在候选药物，目前许多药物正处于临床研究阶段。我们评估了以羟酸盐为基础的HDACi YF-343在三阴性乳腺癌发展中的抗癌功效，并研究了其潜在机制。 方法：通过HDACi药物筛选试剂盒估计YF-343是一种新型HDACi。用Western blot和流式细胞术分析了YF-343在乳腺癌细胞系中的生物学效应。YF-343表现出明显的细胞毒性，促进细胞凋亡，诱导细胞周期阻滞。此外，它还能诱导自噬，这在乳腺癌细胞中起促进生存的作用。 结果: 与单独使用YF-343相比，YF-343联合自噬抑制剂氯喹(CQ)在体内和体外均能显著抑制乳腺癌的进展。在机制上，通过基因芯片表达谱、qPCR分析、荧光素酶报告基因分析、染色质免疫沉淀试验、免疫组织化学分析等方法阐明了YF-343对自噬的分子机制。转录因子E2F7通过结合ATG2A启动子区促进ATG2A的表达，诱导YF-343处理的三阴性乳腺癌细胞自噬。 结论：我们的研究已经阐明了YF-343对具有促生存自噬的乳腺癌模型中肿瘤生长的潜在作用机制。YF-343与CQ联合治疗可能是一种很有前景的乳腺癌治疗策略

关键词: HDACi，三阴性乳腺癌，细胞凋亡，自噬，氯喹，E2F7。

« Previous Next »
[1]
Podo, F.; Buydens, L.M.C.; Degani, H.; Hilhorst, R.; Klipp, E.; Gribbestad, I.S.; Van Huffel, S.; van Laarhoven, H.W.; Luts, J.; Monleon, D.; Postma, G.J.; Schneiderhan-Marra, N.; Santoro, F.; Wouters, H.; Russnes, H.G.; Sørlie, T.; Tagliabue, E.; Børresen-Dale, A.L. Triple-negative breast cancer: present challenges and new perspectives. Mol. Oncol., 2010, 4(3), 209-229.
[http://dx.doi.org/10.1016/j.molonc.2010.04.006] [PMID: 20537966]
[2]
Li, H.; Chen, Y.; Wang, X.; Tang, L.; Guan, X. T1-2N0M0 triple-negative breast cancer treated with breast-conserving therapy has better survival compared to mastectomy: A SEER population-based retrospective analysis. Clin. Breast Cancer, 2019, 19(6), e669-e682.
[http://dx.doi.org/10.1016/j.clbc.2019.05.011] [PMID: 31375327]
[3]
King, T.A.; Li, W.; Brogi, E.; Yee, C.J.; Gemignani, M.L.; Olvera, N.; Levine, D.A.; Norton, L.; Robson, M.E.; Offit, K.; Borgen, P.I.; Boyd, J. Heterogenic loss of the wild-type BRCA allele in human breast tumorigenesis. Ann. Surg. Oncol., 2007, 14(9), 2510-2518.
[http://dx.doi.org/10.1245/s10434-007-9372-1] [PMID: 17597348]
[4]
Huang, Y.; Nayak, S.; Jankowitz, R.; Davidson, N.E.; Oesterreich, S. Epigenetics in breast cancer: what’s new? Breast Cancer Res., 2011, 13(6), 225.
[http://dx.doi.org/10.1186/bcr2925] [PMID: 22078060]
[5]
Feinberg, A.P.; Koldobskiy, M.A.; Göndör, A. Epigenetic modulators, modifiers and mediators in cancer aetiology and progression. Nat. Rev. Genet., 2016, 17(5), 284-299.
[http://dx.doi.org/10.1038/nrg.2016.13] [PMID: 26972587]
[6]
Tessarz, P.; Kouzarides, T. Histone core modifications regulating nucleosome structure and dynamics. Nat. Rev. Mol. Cell Biol., 2014, 15(11), 703-708.
[http://dx.doi.org/10.1038/nrm3890] [PMID: 25315270]
[7]
Li, Y.; Seto, E. HDACs and HDAC inhibitors in cancer development and therapy. Cold Spring Harb. Perspect. Med., 2016, 6(10), a026831.
[http://dx.doi.org/10.1101/cshperspect.a026831] [PMID: 27599530]
[8]
Clements, M.E.; Holtslander, L.; Edwards, C.; Todd, V.; Dooyema, S.D.R.; Bullock, K.; Bergdorf, K.; Zahnow, C.A.; Connolly, R.M.; Johnson, R.W. HDAC inhibitors induce LIFR expression and promote a dormancy phenotype in breast cancer. Oncogene, 2021, 40(34), 5314-5326.
[http://dx.doi.org/10.1038/s41388-021-01931-1] [PMID: 34247191]
[9]
Hou, F.; Li, D.; Yu, H.; Kong, Q. The mechanism and potential targets of class II HDACs in angiogenesis. J. Cell. Biochem., 2018, 119(4), 2999-3006.
[http://dx.doi.org/10.1002/jcb.26476] [PMID: 29091298]
[10]
Khan, O.; La Thangue, N.B. HDAC inhibitors in cancer biology: emerging mechanisms and clinical applications. Immunol. Cell Biol., 2012, 90(1), 85-94.
[http://dx.doi.org/10.1038/icb.2011.100] [PMID: 22124371]
[11]
Gatla, H.R.; Zou, Y.; Uddin, M.M.; Singha, B.; Bu, P.; Vancura, A.; Vancurova, I. Histone deacetylase (HDAC) inhibition induces IκB kinase (IKK)-dependent interleukin-8/CXCL8 expression in dvarian cancer cells. J. Biol. Chem., 2017, 292(12), 5043-5054.
[http://dx.doi.org/10.1074/jbc.M116.771014] [PMID: 28167529]
[12]
Shan, P.; Yang, F.; Qi, H.; Hu, Y.; Zhu, S.; Sun, Z.; Zhang, Z.; Wang, C.; Hou, C.; Yu, J.; Wang, L.; Zhou, Z.; Li, P.; Zhang, H.; Wang, K. Alteration of MDM2 by the small molecule YF438 exerts antitumor effects in triple-negative breast cancer. Cancer Res., 2021, 81(15), 4027-4040.
[http://dx.doi.org/10.1158/0008-5472.CAN-20-0922] [PMID: 33985974]
[13]
Carew, J.S.; Giles, F.J.; Nawrocki, S.T. Histone deacetylase inhibitors: Mechanisms of cell death and promise in combination cancer therapy. Cancer Lett., 2008, 269(1), 7-17.
[http://dx.doi.org/10.1016/j.canlet.2008.03.037] [PMID: 18462867]
[14]
Wagner, J.M.; Hackanson, B.; Lübbert, M.; Jung, M. Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy. Clin. Epigenetics, 2010, 1(3-4), 117-136.
[http://dx.doi.org/10.1007/s13148-010-0012-4] [PMID: 21258646]
[15]
Eskelinen, E.L. The dual role of autophagy in cancer. Curr. Opin. Pharmacol., 2011, 11(4), 294-300.
[http://dx.doi.org/10.1016/j.coph.2011.03.009] [PMID: 21498118]
[16]
Yang, Z.J.; Chee, C.E.; Huang, S.; Sinicrope, F. Autophagy modulation for cancer therapy. Cancer Biol. Ther., 2011, 11(2), 169-176.
[http://dx.doi.org/10.4161/cbt.11.2.14663] [PMID: 21263212]
[17]
Roberts, J.L.; Poklepovic, A.; Booth, L.; Dent, P. The multi-kinase inhibitor lenvatinib interacts with the HDAC inhibitor entinostat to kill liver cancer cells. Cell. Signal., 2020, 70, 109573.
[http://dx.doi.org/10.1016/j.cellsig.2020.109573] [PMID: 32087304]
[18]
Mrakovcic, M.; Kleinheinz, J.; Fröhlich, L. Histone deacetylase inhibitor-induced autophagy in tumor cells: Implications for p53. Int. J. Mol. Sci., 2017, 18(9), 1883.
[http://dx.doi.org/10.3390/ijms18091883] [PMID: 30563957]
[19]
Sun, A.; Bagella, L.; Tutton, S.; Romano, G.; Giordano, A. From G0 to S phase: A view of the roles played by the retinoblastoma (Rb) family members in the Rb-E2F pathway. J. Cell. Biochem., 2007, 102(6), 1400-1404.
[http://dx.doi.org/10.1002/jcb.21609] [PMID: 17979151]
[20]
Polager, S.; Ginsberg, D. E2F – at the crossroads of life and death. Trends Cell Biol., 2008, 18(11), 528-535.
[http://dx.doi.org/10.1016/j.tcb.2008.08.003] [PMID: 18805009]
[21]
Gediya, L.K.; Chopra, P.; Purushottamachar, P.; Maheshwari, N.; Njar, V.C.O. A new simple and high-yield synthesis of suberoylanilide hydroxamic acid and its inhibitory effect alone or in combination with retinoids on proliferation of human prostate cancer cells. J. Med. Chem., 2005, 48(15), 5047-5051.
[http://dx.doi.org/10.1021/jm058214k] [PMID: 16033284]
[22]
Li, J.J.; Zhang, T.; Yang, F.F.; He, Y.; Dai, F.J.; Gao, D.; Chen, Y.; Liu, M.; Yi, Z. Inhibition of breast cancerprogression by a novelhistone deacetylaseinhibitor, LW479, bydown-regulatingEGFR expression. Br. J. Pharmacol., 2015, 15, 3817-3810.
[http://dx.doi.org/10.1111/bph.13165] [PMID: 25884486]
[23]
Australian Bureau of Statistics. The website Australian National Statistical Service Sample Calculator. 2018. Available from: http://www.abs.gov.au/websitedbs/ D3310114. nsf/Home/2016%20TableBuilder/
[24]
Minucci, S.; Pelicci, P.G. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat. Rev. Cancer, 2006, 6(1), 38-51.
[http://dx.doi.org/10.1038/nrc1779] [PMID: 16397526]
[25]
Mrakovcic, M.; Fröhlich, L.F. Molecular determinants of cancer therapy resistance to HDAC inhibitor-induced autophagy. Cancers (Basel), 2019, 12(1), 109.
[http://dx.doi.org/10.3390/cancers12010109] [PMID: 31906235]
[26]
Wu, N.; Li, J.; Luo, H.; Wang, D.; Bai, X. Hydroxysafflor yellow A promotes apoptosis via blocking autophagic flux in liver cancer. Biomed. Pharmacother., 2021, 136, 111227.
[http://dx.doi.org/10.1016/j.biopha.2021.111227] [PMID: 33485070]
[27]
de Bruin, A.; A Cornelissen, P.W.; Kirchmaier, B.C.; Mokry, M.; Iich, E.; Nirmala, E.; Liang, K.H.; D Végh, A.M.; Scholman, K.T.; Groot Koerkamp, M.J.; Holstege, F.C.; Cuppen, E.; Schulte-Merker, S.; Bakker, W.J. Genome-wide analysis reveals NRP1 as a direct HIF1α-E2F7 target in the regulation of motorneuron guidance in vivo. Nucleic Acids Res., 2016, 44(8), 3549-3566.
[http://dx.doi.org/10.1093/nar/gkv1471] [PMID: 26681691]
[28]
Wong, K.K. DNMT1: A key drug target in triple-negative breast cancer. Semin. Cancer Biol., 2021, 72, 198-213.
[http://dx.doi.org/10.1016/j.semcancer.2020.05.010] [PMID: 32461152]
[29]
Yin, L.; Duan, J.J.; Bian, X.W.; Yu, S. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res., 2020, 22(1), 61.
[http://dx.doi.org/10.1186/s13058-020-01296-5] [PMID: 32517735]
[30]
Gupta, G.K.; Collier, A.L.; Lee, D.; Hoefer, R.A.; Zheleva, V.; Siewertsz van Reesema, L.L.; Tang-Tan, A.M.; Guye, M.L.; Chang, D.Z.; Winston, J.S.; Samli, B.; Jansen, R.J.; Petricoin, E.F.; Goetz, M.P.; Bear, H.D.; Tang, A.H. Perspectives on triple-negative breast cancer: current treatment strategies, unmet needs, and potential targets for future therapies. Cancers (Basel), 2020, 12(9), 2392.
[http://dx.doi.org/10.3390/cancers12092392] [PMID: 32846967]
[31]
Li, Y.; Wang, S.; Wei, X.; Zhang, S.; Song, Z.; Chen, X.; Zhang, J. Role of inhibitor of yes-associated protein 1 in triple-negative breast cancer with taxol-based chemoresistance. Cancer Sci., 2019, 110(2), 561-567.
[http://dx.doi.org/10.1111/cas.13888] [PMID: 30467925]
[32]
Shao, Y.; Gao, Z.; Marks, P.A.; Jiang, X. Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Proc. Natl. Acad. Sci. USA, 2004, 101(52), 18030-18035.
[http://dx.doi.org/10.1073/pnas.0408345102] [PMID: 15596714]
[33]
Watanabe, M.; Adachi, S.; Matsubara, H.; Imai, T.; Yui, Y.; Mizushima, Y.; Hiraumi, Y.; Watanabe, K.; Kamitsuji, Y.; Toyokuni, S.; Hosoi, H.; Sugimoto, T.; Toguchida, J.; Nakahata, T. Induction of autophagy in malignant rhabdoid tumor cells by the histone deacetylase inhibitor FK228 through AIF translocation. Int. J. Cancer, 2009, 124(1), 55-67.
[http://dx.doi.org/10.1002/ijc.23897] [PMID: 18821579]
[34]
Taylor, M.A.; Das, B.C.; Ray, S.K. Targeting autophagy for combating chemoresistance and radioresistance in glioblastoma. Apoptosis, 2018, 23(11-12), 563-575.
[http://dx.doi.org/10.1007/s10495-018-1480-9] [PMID: 30171377]
[35]
Mrakovcic, M.; Kleinheinz, J.; Fröhlich, L.F. p53 at the crossroads between different types of HDAC inhibitor-mediated cancer cell death. Int. J. Mol. Sci., 2019, 20(10), 2415.
[http://dx.doi.org/10.3390/ijms20102415] [PMID: 31096697]
[36]
Hamed, H.A.; Das, S.K.; Sokhi, U.K.; Park, M.A.; Cruickshanks, N.; Archer, K.; Ogretmen, B.; Grant, S.; Sarkar, D.; Fisher, P.B.; Dent, P. Combining histone deacetylase inhibitors with MDA-7/IL-24 enhances killing of renal carcinoma cells. Cancer Biol. Ther., 2013, 14(11), 1039-1049.
[http://dx.doi.org/10.4161/cbt.26110] [PMID: 24025359]
[37]
Yang, P.M.; Chen, C.C. Life or death? Autophagy in anticancer therapies with statins and histone deacetylase inhibitors. Autophagy, 2011, 7(1), 107-108.
[http://dx.doi.org/10.4161/auto.7.1.13988] [PMID: 21057221]
[38]
Stankov, M.V.; El Khatib, M.; Kumar Thakur, B.; Heitmann, K.; Panayotova-Dimitrova, D.; Schoening, J.; Bourquin, J.P.; Schweitzer, N.; Leverkus, M.; Welte, K.; Reinhardt, D.; Li, Z.; Orkin, S.H.; Behrens, G.M.N.; Klusmann, J.H. Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy. Leukemia, 2014, 28(3), 577-588.
[http://dx.doi.org/10.1038/leu.2013.264] [PMID: 24080946]
[39]
Lapierre, L.R.; Kumsta, C.; Sandri, M.; Ballabio, A.; Hansen, M. Transcriptional and epigenetic regulation of autophagy in aging. Autophagy, 2015, 11(6), 867-880.
[http://dx.doi.org/10.1080/15548627.2015.1034410] [PMID: 25836756]
[40]
Chen, X.; Zhang, Y.; Shi, Y.; Lian, H.; Tu, H.; Han, S.; Yin, J.; Peng, B.; Zhou, B.; He, X.; Liu, W. MiR-129 triggers autophagic flux by regulating a novel Notch-1/ E2F7/Beclin-1 axis to impair the viability of human malignant glioma cells. Oncotarget, 2016, 7(8), 9222-9235.
[http://dx.doi.org/10.18632/oncotarget.7003] [PMID: 26824182]
[41]
Sun, C.C.; Li, S.J.; Hu, W.; Zhang, J.; Zhou, Q.; Liu, C.; Li, L.L.; Song, Y.Y.; Zhang, F.; Chen, Z.L.; Li, G.; Bi, Z.Y.; Bi, Y.Y.; Gong, F.Y.; Bo, T.; Yuan, Z.P.; Hu, W.D. Comprehensive analysis of the expression and prognosis for E2Fs in human breast cancer. Mol. Ther., 2019, 27, 1153-1165.
[http://dx.doi.org/10.1016/j.ymthe.2019.03.019] [PMID: 31010740]
[42]
Lammens, T.; Li, J.; Leone, G.; De Veylder, L. Atypical E2Fs: new players in the E2F transcription factor family. Trends Cell Biol., 2009, 19(3), 111-118.
[http://dx.doi.org/10.1016/j.tcb.2009.01.002] [PMID: 19201609]
[43]
Morgunova, E.; Yin, Y.; Jolma, A.; Dave, K.; Schmierer, B.; Popov, A.; Eremina, N.; Nilsson, L.; Taipale, J. Structural insights into the DNA-binding specificity of E2F family transcription factors. Nat. Commun., 2015, 6(1), 10050.
[http://dx.doi.org/10.1038/ncomms10050] [PMID: 26632596]
[44]
Weijts, B.G.M.W.; Westendorp, B.; Hien, B.T.; Martínez-López, L.M.; Zijp, M.; Thurlings, I.; Thomas, R.E.; Schulte-Merker, S.; Bakker, W.J.; de Bruin, A. A typical E2Fs inhibit tumor angiogenesis. Oncogene, 2018, 37(2), 271-276.
[http://dx.doi.org/10.1038/onc.2017.336] [PMID: 28925392]
[45]
Moon, N.S.; Dyson, N. E2F7 and E2F8 keep the E2F family in balance. Dev. Cell, 2008, 14(1), 1-3.
[http://dx.doi.org/10.1016/j.devcel.2007.12.017] [PMID: 18194644]
[46]
Staberg, M.; Michaelsen, S.R.; Rasmussen, R.D.; Villingshøj, M.; Poulsen, H.S.; Hamerlik, P. Inhibition of histone deacetylases sensitizes glioblastoma cells to lomustine. Cell Oncol. (Dordr.), 2017, 40(1), 21-32.
[http://dx.doi.org/10.1007/s13402-016-0301-9] [PMID: 27766591]
[47]
Lopez, G.; Torres, K.; Lev, D. Autophagy blockade enhances HDAC inhibitors’ pro-apoptotic effects. Autophagy, 2011, 7(4), 440-441.
[http://dx.doi.org/10.4161/auto.7.4.14680] [PMID: 21224727]
[48]
Körholz, K.; Ridinger, J.; Krunic, D.; Najafi, S.; Gerloff, X.F.; Frese, K.; Meder, B.; Peterziel, H.; VegaRubindeCelis, S.; Witt, Ol.; Oehme, I. Broad-spectrum HDAC inhibitors promote autophagy through FOXO transcription factors in neuroblastoma. Cells, 2021, 10(5), 1001.

Rights & Permissions Print Cite
Article Metrics
74
3
World No Tabaco Day
International No Diet Day
© 2024 Bentham Science Publishers | Privacy Policy