Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Inhibition of Jurkat T Cell Proliferation by Active Components of Rumex japonicus Roots Via Induced Mitochondrial Damage and Apoptosis Promotion

  • Qiu, Yinda (College of Pharmacy, Chonnam National University) ;
  • Li, Aoding (College of Pharmacy, Chonnam National University) ;
  • Lee, Jina (Biometrology Group, Korea Research Institute of Standards and Science (KRISS)) ;
  • Lee, Jeong Eun (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Lee, Eun-Woo (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Cho, Namki (College of Pharmacy, Chonnam National University) ;
  • Yoo, Hee Min (Biometrology Group, Korea Research Institute of Standards and Science (KRISS))
  • Received : 2020.07.14
  • Accepted : 2020.10.18
  • Published : 2020.12.28
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Abstract

Rumex japonicus Houtt (RJH) is a valuable plant used in traditional medicine to treat several diseases, such as scabies and jaundice. In this study, Jurkat cell growth inhibitory extracts of R. japonicus roots were subjected to bioassay-guided fractionation, resulting in the isolation of three naphthalene derivatives (3-5) along with one anthraquinone (6) and two phenolic compounds (1 and 2). Among these compounds, 2-methoxystypandrone (5) exhibited potent anti-proliferative effects on Jurkat cells. Analysis by flow cytometry confirmed that 2-methoxystypandrone (5) could significantly reduce mitochondrial membrane potential and promote increased levels of mitochondrial reactive oxygen species (ROS), suggesting a strong mitochondrial depolarization effect. Real-time quantitative polymerase chain reaction (qPCR) analysis was also performed, and the results revealed that the accumulation of ROS was caused by reduced mRNA expression levels of heme oxygenase (HO-1), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, 2-methoxystypandrone (5) triggered strong apoptosis that was mediated by the arrest of the G0/G1 phase of the cell cycle. Furthermore, 2-methoxystypandrone (5) downregulated p-IκB-α, p-NF-κB p65, Bcl2, and Bcl-xl and upregulated BAX proteins. Taken together, these findings revealed that 2-methoxystypandrone (5) isolated from RJH could potentially serve as an early lead compound for leukemia treatment involving intracellular signaling by increasing mitochondrial ROS and exerting anti-proliferative effects.

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References

  1. Freireich, EJ, Wiernik PH, Steensma DP. 2014. The leukemias: a half-century of discovery. J. Clin. Oncol. 32: 3463-3469. https://doi.org/10.1200/JCO.2014.57.1034
  2. Lee J-E, Thuy NTT, Lee J, Cho N, Yoo HM. 2019. Platyphylloside isolated from betula platyphylla is antiproliferative and induces apoptosis in colon cancer and leukemic cells. Molecules 24: 2960. https://doi.org/10.3390/molecules24162960
  3. Greaves M. 2016. Leukaemia "firsts" in cancer research and treatment. Nat. Rev. Cancer 16: 163-172. https://doi.org/10.1038/nrc.2016.3
  4. Lee J-E, Thanh Thuy NT, Lee Y, Cho N, Yoo HM. 2020. An Antiproliferative ent -kaurane diterpene isolated from the roots of mallotus japonicus induced apoptosis in leukemic cells. Nat. Prod. Commun. 15: 1934578X1989749. https://doi.org/10.1177/1934578x19897496
  5. Guo J, Cahill MR, McKenna SL, O'Driscoll CM. 2014. Biomimetic nanoparticles for siRNA delivery in the treatment of leukaemia. Biotechnol. Adv. 32: 1396-1409. https://doi.org/10.1016/j.biotechadv.2014.08.007
  6. Prakash O, Kumar A, Kumar P, Ajeet A. 2013. Anticancer potential of plants and natural products: a review. Am. J. Pharmacol. Sci. 1: 104-115. https://doi.org/10.12691/ajps-1-6-1
  7. Cui L, Bu W, Song J, Feng L, Xu T, Liu D, et al. 2018. Apoptosis induction by alantolactone in breast cancer MDA-MB-231 cells through reactive oxygen species-mediated mitochondrion-dependent pathway. Arch. Pharm. Res. 41: 299-313. https://doi.org/10.1007/s12272-017-0990-2
  8. Ye YC, Wang HJ, Yu L, Tashiro SI, Onodera, Ikejima T. 2012. RIP1-mediated mitochondrial dysfunction and ROS production contributed to tumor necrosis factor alpha-induced L929 cell necroptosis and autophagy. Int. Immunopharmacol. 14: 674-682. https://doi.org/10.1016/j.intimp.2012.08.003
  9. Ly JD, Grubb DR, Lawen A. 2003. The mitochondrial membrane potential (δψm) in apoptosis; an update. Apotosis 8: 115-128. https://doi.org/10.1023/A:1022945107762
  10. Jeong SY, Seol DW. 2008. The role of mitochondria in apoptosis. BMB Rep. 41: 11-22. https://doi.org/10.5483/BMBRep.2008.41.1.011
  11. Zhang BB, Wang, D gang, Guo F-fen, Xuan C. 2015. Mitochondrial membrane potential and reactive oxygen species in cancer stem cells. Farm. Cancer 14: 19-23.
  12. Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN, et al. 2009. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458: 780-783. https://doi.org/10.1038/nature07733
  13. Youn J-S, Yang J, Kim S-C, Pak J-H. 2019. Complete plastome sequence of Rumex japonicus (Polygonaceae) in Dok-do Island, Korea. Mitochondrial DNA Part B. 4: 2892-2893. https://doi.org/10.1080/23802359.2019.1660274
  14. Elzaawely AA, Xuan TD, Tawata S. 2005. Antioxidant and antibacterial activities of Rumex japonicus HOUTT. aerial parts. Biol. Pharm. Bull. 28: 2225-2230. https://doi.org/10.1248/bpb.28.2225
  15. Liang HX, Dai HQ, Fu HA, Dong XP, Adebayo AH, Zhang LX, et al. Phytochem. Lett. 3: 181-184. https://doi.org/10.1016/j.phytol.2010.05.005
  16. Sun Y, Lenon GB, Yang AWH. 2020. Rumex japonicus Houtt.: a phytochemical, pharmacological, and pharmacokinetic review. Phyther. Res. 34: 1198-1215. https://doi.org/10.1002/ptr.6601
  17. Vasas A, Orban-Gyapai O, Hohmann J. 2015. The Genus Rumex: review of traditional uses, phytochemistry and pharmacology. J. Ethnopharmacol.175: 198-228. https://doi.org/10.1016/j.jep.2015.09.001
  18. Chung TW, Lee J H, Choi HJ, Park MJ, Kim EY, Han JH, et al. 2017. Anemone rivularis inhibits pyruvate dehydrogenase kinase activity and tumor growth. J. Ethnopharmacol. 203: 47-54. https://doi.org/10.1016/j.jep.2017.03.034
  19. Luo Z, Xu X, Sho T, Zhang J, Xu W, Yao J, et al. 2019. ROS-induced autophagy regulates porcine trophectoderm cell apoptosis, proliferation, and differentiation. Am. J. Physiol. Cell Physiol. 316: C198-C209. https://doi.org/10.1152/ajpcell.00256.2018
  20. Yang Z, Pan Q, Zhang D, Chen J, Qiu Y, Chen X, et al. 2019. Silibinin restores the sensitivity of cisplatin and taxol in A2780-resistant cell and reduces drug-induced hepatotoxicity. Cancer Manag. Res. 11: 7111-7122. https://doi.org/10.2147/CMAR.S201341
  21. Fatfat M, Fakhoury I, Habli Z, Mismar R, Gali-Muhtasib H. 2019. Thymoquinone enhances the anticancer activity of doxorubicin against adult T-cell leukemia in vitro and in vivo through ROS-dependent mechanisms. Life Sci. 232:116628. https://doi.org/10.1016/j.lfs.2019.116628
  22. Chen H, Zhang Y, Zhang W, Liu H, Sun C, Zhang B, et al. 2019. Inhibition of myeloid differentiation factor 2 by baicalein protects against acute lung injury. Phytomedicine 63:152997. https://doi.org/10.1016/j.phymed.2019.152997
  23. Tabuchi H, Tajimi A, Ichihara A. 2014. Phytotoxic Metabolites Isolated from Scolecotrichum graminis Fuckel. Biosci. Biotechnol. Biochem. 58: 1956-1959. https://doi.org/10.1271/bbb.58.1956
  24. Nishina A, Kubota K, Osawa T. 1993. Antimicrobial components, trachrysone and 2-methoxystypandrone, in Rumex japonicus Houtt. J. Agric. Food Chem. 41: 1772-1775. https://doi.org/10.1021/jf00034a047
  25. GUPTA SK. Ascorbic Acid - Natural Sugar Lactone Esters for Comprehensive Skin & Scalp Care. U.S. Patent Application No. 12/139,659.
  26. Guo S, Feng B, Zhu R, Ma J, Wang W. 2011. Preparative isolation of three anthraquinones from Rumex japonicus by high-speed counter-current chromatography. Molecules 16: 1201-1210. https://doi.org/10.3390/molecules16021201
  27. Hydbring P, Malumbres M, Sicinski P. 2016. Non-canonical functions of cell cycle cyclins and cyclin-dependent kinases. Nat. Rev. Mol. Cell Biol. 17: 280-292. https://doi.org/10.1038/nrm.2016.27
  28. Otto T, Sicinski P. 2017. Cell cycle proteins as promising targets in cancer therapy. Nat. Rev. Cancer 17: 93-115. https://doi.org/10.1038/nrc.2016.138
  29. Ichim G, Tait SWG. 2016. A fate worse than death: apoptosis as an oncogenic process. Nat. Rev. Cancer 16: 539-548. https://doi.org/10.1038/nrc.2016.58
  30. Seo J, Kim MW, Bae KH, Lee SC, Song J, Lee EW. 2019. The roles of ubiquitination in extrinsic cell death pathways and its implications for therapeutics. Biochem. Pharmacol. 162: 21-40. https://doi.org/10.1016/j.bcp.2018.11.012
  31. Busuttil V, Bottero V, Frelin C, Imbert V, Ricci JE, Auberger P, et al. 2002. Blocking NF-κB activation in Jurkat leukemic T cells converts the survival agent and tumor promoter PMA into an apoptotic effector. Oncogene 21: 3213-3224. https://doi.org/10.1038/sj/onc/1205433
  32. Espinosa L, Bigas A, Mulero MC. 2014. Novel functions of chromatin-bound IκBα in oncogenic transformation. Br. J. Cancer 111: 1688-1692. https://doi.org/10.1038/bjc.2014.84
  33. Yu AF, Ky B. 2016. Roadmap for biomarkers of cancer therapy cardiotoxicity. Heart 102: 425-430. https://doi.org/10.1136/heartjnl-2015-307894
  34. Comazzi S, Aresu L, Marconato L. 2015. Transformation of canine lymphoma/leukemia to more aggressive diseases: anecdotes or reality? Front. Vet. Sci. 2: 42. https://doi.org/10.3389/fvets.2015.00042
  35. Zaidman BZ, Yassin M, Mahajna J, Wasser SP. 2005. Medicinal mushroom modulators of molecular targets as cancer therapeutics. Appl. Microbiol. Biotechnol. 67: 453-468. https://doi.org/10.1007/s00253-004-1787-z
  36. Itoigawa M. 2001. Cancer chemopreventive activity of naphthoquinones and their analogs from Avicennia plants. Cancer Lett. 174: 135-139. https://doi.org/10.1016/S0304-3835(01)00707-8
  37. Widhalm JR, Rhodes D. 2016. Biosynthesis and molecular actions of specialized 1,4-naphthoquinone natural products produced by horticultural plants. Hortic. Res. 3: 16046. https://doi.org/10.1038/hortres.2016.46
  38. Abraham RT, Weiss A. Jurkat T cells and development of the T-cell receptor signalling paradigm. Nat. Rev. Immunol. 4: 301-308. https://doi.org/10.1038/nri1330
  39. Thuy NTT, Lee JE, Yoo HM, Cho N. 2019. Antiproliferative pterocarpans and coumestans from lespedeza bicolor. J. Nat. Prod. 82: 3025-3032. https://doi.org/10.1021/acs.jnatprod.9b00567
  40. Kuang S, Qi C, Liu J, Sun X, Zhang Q, Sima Z, et al. 2014. 2-Methoxystypandrone inhibits signal transducer and activator of transcription 3 and nuclear factor-κB signaling by inhibiting Janus kinase 2 and IκB kinase. Cancer Sci. 105: 473-480. https://doi.org/10.1111/cas.12359
  41. Alenzi FQB. 2004. Links between apoptosis, proliferation and the cell cycle. Br.J. Biomed. Sci. 61: 99-102. https://doi.org/10.1080/09674845.2004.11732652
  42. Pietenpol JA, Stewart ZA. 2002. Cell cycle checkpoint signaling: cell cycle arrest versus apoptosis. Toxicology 181-182: 475-481. https://doi.org/10.1016/S0300-483X(02)00460-2
  43. Radha G, Raghavan SC. 2017. BCL2: a promising cancer therapeutic target. Biochim. Biophys Acta Rev. Cancer 1868: 309-314. https://doi.org/10.1016/j.bbcan.2017.06.004
  44. Yousef BA, Hassan HM, Zhang L-Y, Jiang Z-Z. 2018. Pristimerin exhibits in vitro and in vivo anticancer activities through inhibition of nuclear factor-κB signaling pathway in colorectal cancer cells. Phytomedicine 40: 140-147. https://doi.org/10.1016/j.phymed.2018.01.008
  45. Liang Y, Feng G, Wu L, Zhong S, Gao X, Tong Y, et al. 2019. Caffeic acid phenethyl ester suppressed growth and metastasis of nasopharyngeal carcinoma cells by inactivating the NF-κB pathway. Drug Des. Devel. Ther. 13: 1335-1345. https://doi.org/10.2147/DDDT.S199182
  46. Ye XQ, Li Q, Wang GH, Sun FF, Huang GJ, Bian XW, et al. S. 2011. Mitochondrial and energy metabolism-related properties as novel indicators of lung cancer stem cells. Int. J. Cancer 129: 820-831. https://doi.org/10.1002/ijc.25944
  47. Sun J, Wei X, Lu Y, Cui M, Li F, Lu J, et al. 2017. Glutaredoxin 1 (GRX1) inhibits oxidative stress and apoptosis of chondrocytes by regulating CREB/HO-1 in osteoarthritis. Mol. Immunol. 90: 211-218. https://doi.org/10.1016/j.molimm.2017.08.006
  48. Wang S, He G, Chen,M, Zuo T, Xu W, Liu, X. 2017. The role of antioxidant enzymes in the ovaries. Oxid. Med. Cell. Longev. 2017: 4371714.