Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Chelidonium majus Induces Apoptosis of Human Ovarian Cancer Cells via ATF3-Mediated Regulation of Foxo3a by Tip60

  • Shen, Lei (Aerospace Center Hospital) ;
  • Lee, Soon (Division of Analytical Science, Korea Basic Science Institute) ;
  • Joo, Jong Cheon (Department of Sasang Constitutional Medicine, College of Korean Medicine, Wonkwang University) ;
  • Hong, Eunmi (Division of Analytical Science, Korea Basic Science Institute) ;
  • Cui, Zhen Yang (Rehabilitation Medicine College, Weifang Medical University) ;
  • Jo, Eunbi (Department of Life Science and Research Institute for Natural Sciences, College of Natural Sciences, Hanyang University) ;
  • Park, Soo Jung (Department of Sasang Constitutional Medicine, College of Korean Medicine, Woosuk University) ;
  • Jang, Hyun-Jin (Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2021.09.15
  • Accepted : 2022.02.14
  • Published : 2022.04.28
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Abstract

Forkhead transcription factor 3a (Foxo3a) is believed to be a tumor suppressor as its inactivation leads to cell transformation and tumor development. However, further investigation is required regarding the involvement of the activating transcription factor 3 (ATF3)-mediated Tat-interactive protein 60 (Tip60)/Foxo3a pathway in cancer cell apoptosis. This study demonstrated that Chelidonium majus upregulated the expression of ATF3 and Tip60 and promoted Foxo3a nuclear translocation, ultimately increasing the level of Bcl-2-associated X protein (Bax) protein. ATF3 overexpression stimulated Tip60 expression, while ATF3 inhibition by siRNA repressed Tip60 expression. Furthermore, siRNA-mediated Tip60 inhibition significantly promoted Foxo3a phosphorylation, leading to blockade of Foxo3a translocation into the nucleus. Thus, we were able to deduce that ATF3 mediates the regulation of Foxo3a by Tip60. Moreover, siRNA-mediated Foxo3a inhibition suppressed the expression of Bax and subsequent apoptosis. Taken together, our data demonstrate that Chelidonium majus induces SKOV-3 cell death by increasing ATF3 levels and its downstream proteins Tip60 and Foxo3a. This suggests a potential therapeutic role of Chelidonium majus against ovarian cancer.

Keywords

Acknowledgement

With deep sadness we announce the sudden death of our colleague Dr. Ik-Soon Jang, who started and led this Chelidonium majus project. All authors will remember him as our scientific leader, friend, and colleague. This paper was supported by Wonkwang University in 2020.

References

  1. Zhou Q, Liu Y, Wang X, Di X. 2012. Microwave-assisted extraction in combination with capillary electrophoresis for rapid determination of isoquinoline alkaloids in Chelidonium majus L. Talanta 99: 932-938. https://doi.org/10.1016/j.talanta.2012.07.061
  2. El-Readi MZ, Eid S, Ashour ML, Tahrani A, Wink M. 2013. Modulation of multidrug resistance in cancer cells by chelidonine and Chelidonium majus alkaloids. Phytomedicine 20: 282-294. https://doi.org/10.1016/j.phymed.2012.11.005
  3. Van Wyk B-E, Wink M. 2004. Medicinal plants of the world : an illustrated scientific guide to important medicinal plants and their uses, pp. 102. 1st Ed. Timber Press, Portland.
  4. Kohn L. 2005. Health and long life the Chinese way, pp. 131. 1st Ed. Three Pines Press, Cambridge, MA., USA.
  5. Deljanin M, Nikolic M, Baskic D, Todorovic D, Djurdjevic P, Zaric M, et al. 2016. Chelidonium majus crude extract inhibits migration and induces cell cycle arrest and apoptosis in tumor cell lines. J. Ethnopharmacol. 190: 362-371. https://doi.org/10.1016/j.jep.2016.06.056
  6. Herrmann R, Roller J, Polednik C, Schmidt M. 2018. Effect of chelidonine on growth, invasion, angiogenesis and gene expression in head and neck cancer cell lines. Oncol. Lett. 16: 3108-3116.
  7. Capistrano IR, Wouters A, Lardon F, Gravekamp C, Apers S, Pieters L. 2015. In vitro and in vivo investigations on the antitumour activity of Chelidonium majus. Phytomedicine 22: 1279-1287. https://doi.org/10.1016/j.phymed.2015.10.013
  8. Xie YJ, Gao WN, Wu QB, Yao XJ, Jiang ZB, Wang YW, et al. 2020. Chelidonine selectively inhibits the growth of gefitinib-resistant non-small cell lung cancer cells through the EGFR-AMPK pathway. Pharmacol. Res. 159: 104934. https://doi.org/10.1016/j.phrs.2020.104934
  9. Havelek R, Seifrtova M, Kralovec K, Krocova E, Tejkalova V, Novotny I, et al. 2016. Comparative cytotoxicity of chelidonine and homochelidonine, the dimethoxy analogues isolated from Chelidonium majus L. (Papaveraceae), against human leukemic and lung carcinoma cells. Phytomedicine 23: 253-266. https://doi.org/10.1016/j.phymed.2016.01.001
  10. Panzer A, Joubert AM, Bianchi PC, Hamel E, Seegers JC. 2001. The effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways. Eur. J. Cell Biol. 80: 111-118. https://doi.org/10.1078/0171-9335-00135
  11. Colombo ML, Bosisio E. 1996. Pharmacological activities of Chelidonium majus L. (Papaveraceae). Pharmacol. Res. 33: 127-134. https://doi.org/10.1006/phrs.1996.0019
  12. Gilca M, Gaman L, Panait E, Stoian I, Atanasiu V. 2010. Chelidonium majus--an integrative review: traditional knowledge versus modern findings. Forsch. Komplementmed. 17: 241-248. https://doi.org/10.1159/000321397
  13. Kokoska L, Polesny Z, Rada V, Nepovim A, Vanek T. 2002. Screening of some Siberian medicinal plants for antimicrobial activity. J. Ethnopharmacol. 82: 51-53. https://doi.org/10.1016/S0378-8741(02)00143-5
  14. Lee YC, Kim SH, Roh SS, Choi HY, Seo YB. 2007. Suppressive effects of Chelidonium majus methanol extract in knee joint, regional lymph nodes, and spleen on collagen-induced arthritis in mice. J. Ethnopharmacol. 112: 40-48. https://doi.org/10.1016/j.jep.2007.01.033
  15. Noureini SK, Wink M. 2009. Transcriptional down regulation of hTERT and senescence induction in HepG2 cells by chelidonine. World J. Gastroenterol. 15: 3603-3610. https://doi.org/10.3748/wjg.15.3603
  16. Lu JJ, Bao JL, Chen XP, Huang M, Wang YT. 2012. Alkaloids isolated from natural herbs as the anticancer agents. Evid. Based Complement. Alternat. Med. 2012: 485042.
  17. Kim O, Hwangbo C, Kim J, Li DH, Min BS, Lee JH. 2015. Chelidonine suppresses migration and invasion of MDA-MB-231 cells by inhibiting formation of the integrin-linked kinase/PINCH/alpha-parvin complex. Mol. Med. Rep. 12: 2161-2168. https://doi.org/10.3892/mmr.2015.3621
  18. Noureini SK, Esmaili H. 2014. Multiple mechanisms of cell death induced by chelidonine in MCF-7 breast cancer cell line. Chem. Biol. Interact. 223: 141-149. https://doi.org/10.1016/j.cbi.2014.09.013
  19. Lee KS, Kim SW, Lee HS. 2018. Orostachys japonicus induce p53-dependent cell cycle arrest through the MAPK signaling pathway in OVCAR-3 human ovarian cancer cells. Food Sci. Nutr. 6: 2395-2401. https://doi.org/10.1002/fsn3.836
  20. Noureini SK, Esmaeili H, Abachi F, Khiali S, Islam B, Kuta M, et al. 2017. Selectivity of major isoquinoline alkaloids from Chelidonium majus towards telomeric G-quadruplex: A study using a transition-FRET (t-FRET) assay. Biochim. Biophys. Acta Gen. Subj. 1861: 2020-2030. https://doi.org/10.1016/j.bbagen.2017.05.002
  21. Zhang LQ, Lv RW, Qu XD, Chen XJ, Lu HS, Wang Y. 2017. Aloesin suppresses cell growth and metastasis in ovarian cancer SKOV3 cells through the inhibition of the MAPK signaling pathway. Anal. Cell Pathol. (Amst). 2017: 8158254. https://doi.org/10.1155/2017/8158254
  22. Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. 2019. Ovarian cancer in the world: epidemiology and risk factors. Int. J. Womens Health 11: 287-299. https://doi.org/10.2147/IJWH.S197604
  23. Cho KR. 2009. Ovarian cancer update: lessons from morphology, molecules, and mice. Arch. Pathol. Lab Med. 133: 1775-1781. https://doi.org/10.5858/133.11.1775
  24. Karges DE. 2005. Current concepts for treatment of the painful flatfoot in the elderly. Mo. Med. 102: 236-239.
  25. Salzberg M, Thurlimann B, Bonnefois H, Fink D, Rochlitz C, von Moos R, et al. 2005. Current concepts of treatment strategies in advanced or recurrent ovarian cancer. Oncology 68: 293-298. https://doi.org/10.1159/000086967
  26. Jiang X, Kim KJ, Ha T, Lee SH. 2016. Potential dual role of activating transcription factor 3 in colorectal cancer. Anticancer Res. 36: 509-516.
  27. Liang G, Wolfgang CD, Chen BP, Chen TH, Hai T. 1996. ATF3 gene. Genomic organization, promoter, and regulation. J. Biol. Chem. 271: 1695-1701. https://doi.org/10.1074/jbc.271.3.1695
  28. Hai T, Hartman MG. 2001. The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis. Gene 273: 1-11. https://doi.org/10.1016/S0378-1119(01)00551-0
  29. Thompson MR, Xu D, Williams BR. 2009. ATF3 transcription factor and its emerging roles in immunity and cancer. J. Mol. Med (Berl) 87: 1053-1060. https://doi.org/10.1007/s00109-009-0520-x
  30. Wang Z, Yan C. 2016. Emerging roles of ATF3 in the suppression of prostate cancer. Mol. Cell. Oncol. 3: e1010948. https://doi.org/10.1080/23723556.2015.1010948
  31. Yin X, Dewille JW, Hai T. 2008. A potential dichotomous role of ATF3, an adaptive-response gene, in cancer development. Oncogene 27: 2118-2127. https://doi.org/10.1038/sj.onc.1210861
  32. Bassi C, Li YT, Khu K, Mateo F, Baniasadi PS, Elia A, et al. 2016. The acetyltransferase Tip60 contributes to mammary tumorigenesis by modulating DNA repair. Cell Death Differ. 23: 1198-1208. https://doi.org/10.1038/cdd.2015.173
  33. Jang SM, Kim JW, Kim CH, An JH, Johnson A, Song PI, et al. 2015. KAT5-mediated SOX4 acetylation orchestrates chromatin remodeling during myoblast differentiation. Cell Death Dis. 6: e1857. https://doi.org/10.1038/cddis.2015.190
  34. Litvinov IV, Netchiporouk E, Cordeiro B, Zargham H, Pehr K, Gilbert M, et al. 2014. Ectopic expression of embryonic stem cell and other developmental genes in cutaneous T-cell lymphoma. Oncoimmunology 3: e970025. https://doi.org/10.4161/21624011.2014.970025
  35. Mattera L, Escaffit F, Pillaire MJ, Selves J, Tyteca S, Hoffmann JS, et al. 2009. The p400/Tip60 ratio is critical for colorectal cancer cell proliferation through DNA damage response pathways. Oncogene 28: 1506-1517. https://doi.org/10.1038/onc.2008.499
  36. Pandey AK, Zhang Y, Zhang S, Li Y, Tucker-Kellogg G, Yang H, et al. 2015. TIP60-miR-22 axis as a prognostic marker of breast cancer progression. Oncotarget 6: 41290-41306. https://doi.org/10.18632/oncotarget.5636
  37. Judes G, Rifai K, Ngollo M, Daures M, Bignon YJ, Penault-Llorca F, et al. 2015. A bivalent role of TIP60 histone acetyl transferase in human cancer. Epigenomics 7: 1351-1363. https://doi.org/10.2217/epi.15.76
  38. Huang H, Tindall DJ. 2007. Dynamic FoxO transcription factors. J. Cell Sci. 120: 2479-2487. https://doi.org/10.1242/jcs.001222
  39. Maiese K, Chong ZZ, Hou J, Shang YC. 2009. The "O" class: crafting clinical care with FoxO transcription factors. Adv. Exp. Med. Biol. 665: 242-260. https://doi.org/10.1007/978-1-4419-1599-3_18
  40. Guo S, Sonenshein GE. 2004. Forkhead box transcription factor FOXO3a regulates estrogen receptor alpha expression and is repressed by the Her-2/neu/phosphatidylinositol 3-kinase/Akt signaling pathway. Mol. Cell. Biol. 24: 8681-8690. https://doi.org/10.1128/MCB.24.19.8681-8690.2004
  41. Fernandez de Mattos S, Villalonga P, Clardy J, Lam EW. 2008. FOXO3a mediates the cytotoxic effects of cisplatin in colon cancer cells. Mol. Cancer Ther. 7: 3237-3246. https://doi.org/10.1158/1535-7163.MCT-08-0398
  42. Shukla S, Bhaskaran N, Babcook MA, Fu P, Maclennan GT, Gupta S. 2014. Apigenin inhibits prostate cancer progression in TRAMP mice via targeting PI3K/Akt/FoxO pathway. Carcinogenesis 35: 452-460. https://doi.org/10.1093/carcin/bgt316
  43. Yu DS, Chen YT, Wu CL, Yu CP. 2017. Expression of p-FOXO3/FOXO3 in bladder cancer and its correlation with clinicopathology and tumor recurrence. Int. J. Clin. Exp. Pathol. 10: 11069-11074.
  44. Taylor S, Lam M, Pararasa C, Brown JE, Carmichael AR, Griffiths HR. 2015. Evaluating the evidence for targeting FOXO3a in breast cancer: a systematic review. Cancer Cell Int. 15: 1. https://doi.org/10.1186/s12935-015-0156-6
  45. Jang HJ, Yang KE, Oh WK, Lee SI, Hwang IH, Ban KT, et al. 2019. Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels. Aging (Albany NY). 11: 3731-3749. https://doi.org/10.18632/aging.102013
  46. Park S, Kim JM, Shin W, Han SW, Jeon M, Jang HJ, et al. 2018. BTNET : boosted tree based gene regulatory network inference algorithm using time-course measurement data. BMC Syst. Biol. 12: 20. https://doi.org/10.1186/s12918-018-0547-0
  47. Wilson AP. 1984. Characterization of a cell line derived from the ascites of a patient with papillary serous cystadenocarcinoma of the ovary. J. Natl. Cancer Inst. 72: 513-521.
  48. Mikolajczak PL, Kedzia B, Ozarowski M, Kujawski R, Bogacz A, Bartkowiak-Wieczorek J, et al. 2015. Evaluation of anti-inflammatory and analgesic activities of extracts from herb of Chelidonium majus L. Cent Eur. J. Immunol. 40: 400-410.
  49. Isolani ME, Pietra D, Balestrini L, Borghini A, Deri P, Imbriani M, et al. 2012. The in vivo effect of chelidonine on the stem cell system of planarians. Eur. J. Pharmacol. 686: 1-7. https://doi.org/10.1016/j.ejphar.2012.03.036
  50. Xie JJ, Xie YM, Chen B, Pan F, Guo JC, Zhao Q, et al. 2014. ATF3 functions as a novel tumor suppressor with prognostic significance in esophageal squamous cell carcinoma. Oncotarget 5: 8569-8582. https://doi.org/10.18632/oncotarget.2322
  51. Huang X, Li X, Guo B. 2008. KLF6 induces apoptosis in prostate cancer cells through up-regulation of ATF3. J. Biol. Chem. 283: 29795-29801. https://doi.org/10.1074/jbc.M802515200
  52. Zhang X, Tang N, Hadden TJ, Rishi AK. 2011. Akt, FoxO and regulation of apoptosis. Biochim. Biophys. Acta. 1813: 1978-1986. https://doi.org/10.1016/j.bbamcr.2011.03.010
  53. Li Z, Zhang H, Chen Y, Fan L, Fang J. 2012. Forkhead transcription factor FOXO3a protein activates nuclear factor kappaB through B-cell lymphoma/leukemia 10 (BCL10) protein and promotes tumor cell survival in serum deprivation. J. Biol. Chem. 287: 17737-17745. https://doi.org/10.1074/jbc.M111.291708
  54. Gong C, Khoo US. 2013. Nuclear localization marker of FOXO3a: Can it be used to predict doxorubicin response? Front. Oncol. 3: 149. https://doi.org/10.3389/fonc.2013.00149
  55. Das TP, Suman S, Alatassi H, Ankem MK, Damodaran C. 2016. Inhibition of AKT promotes FOXO3a-dependent apoptosis in prostate cancer. Cell Death Dis. 7: e2111. https://doi.org/10.1038/cddis.2015.403
  56. Sunters A, Madureira PA, Pomeranz KM, Aubert M, Brosens JJ, Cook SJ, et al. 2006. Paclitaxel-induced nuclear translocation of FOXO3a in breast cancer cells is mediated by c-Jun NH2-terminal kinase and Akt. Cancer Res. 66: 212-220. https://doi.org/10.1158/0008-5472.CAN-05-1997
  57. Wilk A, Urbanska K, Grabacka M, Mullinax J, Marcinkiewicz C, Impastato D, et al. 2012. Fenofibrate-induced nuclear translocation of FoxO3A triggers Bim-mediated apoptosis in glioblastoma cells in vitro. Cell Cycle. 11: 2660-2671. https://doi.org/10.4161/cc.21015
  58. Bowman KR, Kim JH, Lim CS. 2019. Narrowing the field: cancer-specific promoters for mitochondrially-targeted p53-BH3 fusion gene therapy in ovarian cancer. J. Ovarian Res. 12: 38. https://doi.org/10.1186/s13048-019-0514-4
  59. Tang Y, Luo J, Zhang W, Gu W. 2006. Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis. Mol. Cell. 24: 827-839. https://doi.org/10.1016/j.molcel.2006.11.021
  60. Imamura Y, Mukohara T, Shimono Y, Funakoshi Y, Chayahara N, Toyoda M, et al. 2015. Comparison of 2D- and 3D-culture models as drug-testing platforms in breast cancer. Oncol. Rep. 33: 1837-1843. https://doi.org/10.3892/or.2015.3767
  61. Nowacka M, Sterzynska K, Andrzejewska M, Nowicki M, Januchowski R. 2021. Drug resistance evaluation in novel 3D in vitro model. Biomed. Pharmacother. 138: 111536. https://doi.org/10.1016/j.biopha.2021.111536