Journal of Microbiology and Biotechnology

  • 제32권7호
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  • Pages.918-926
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  • 2022
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  • 1017-7825(pISSN)
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  • 1738-8872(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
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Induction of Cell Cycle Arrest, Apoptosis, and Reducing the Expression of MCM Proteins in Human Lung Carcinoma A549 Cells by Cedrol, Isolated from Juniperus chinensis

  • Yun, Hee Jung (Biopharmaceutical Engineering Major, Division of Applied Bioengineering, College of Engineering, Dong-eui University) ;
  • Jeoung, Da Jeoung (Department of Biopharmaceutics, Dong-eui University Graduate School) ;
  • Jin, Soojung (Core-Facility Center for Tissue Regeneration, Dong-eui University) ;
  • Park, Jung-ha (Biopharmaceutical Engineering Major, Division of Applied Bioengineering, College of Engineering, Dong-eui University) ;
  • Lee, Eun-Woo (Biopharmaceutical Engineering Major, Division of Applied Bioengineering, College of Engineering, Dong-eui University) ;
  • Lee, Hyun-Tai (Biopharmaceutical Engineering Major, Division of Applied Bioengineering, College of Engineering, Dong-eui University) ;
  • Choi, Yung Hyun (Core-Facility Center for Tissue Regeneration, Dong-eui University) ;
  • Kim, Byung Woo (Biopharmaceutical Engineering Major, Division of Applied Bioengineering, College of Engineering, Dong-eui University) ;
  • Kwon, Hyun Ju (Biopharmaceutical Engineering Major, Division of Applied Bioengineering, College of Engineering, Dong-eui University)
  • 투고 : 2022.05.10
  • 심사 : 2022.06.29
  • 발행 : 2022.07.28
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초록

Proteins related to DNA replication have been proposed as cancer biomarkers and targets for anticancer agents. Among them, minichromosome maintenance (MCM) proteins, often overexpressed in various cancer cells, are recognized both as notable biomarkers for cancer diagnosis and as targets for cancer treatment. Here, we investigated the activity of cedrol, a single compound isolated from Juniperus chinensis, in reducing the expression of MCM proteins in human lung carcinoma A549 cells. Remarkably, cedrol also strongly inhibited the expression of all other MCM protein family members in A549 cells. Moreover, cedrol treatment reduced cell viability in A549 cells, accompanied by cell cycle arrest at the G1 phase, and enhanced apoptosis. Taken together, this study broadens our understanding of how cedrol executes its anticancer activity while demonstrating that cedrol has potential application in the treatment of human lung cancer as an inhibitor of MCM proteins.

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과제정보

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant No. NRF-2017R1D1A1B04034994).

참고문헌

  1. Neves H, Kwok HF. 2017. In sickness and in health: the many roles of the minichromosome maintenance proteins. Biochim. Biophys. Acta Rev. Cancer 1868: 295-308. https://doi.org/10.1016/j.bbcan.2017.06.001
  2. Nasheuer HP, Smith R, Bauerschmidt C, Grosse F, Weisshart K. 2002. Initiation of eukaryotic DNA replication: regulation and mechanisms. Prog. Nucleic Acid Res. Mol. Biol. 72: 41-94. https://doi.org/10.1016/S0079-6603(02)72067-9
  3. Blow JJ, Dutta A. 2005. Preventing re-replication of chromosomal DNA. Nat. Rev. Mol. Cell Biol. 6: 476-486. https://doi.org/10.1038/nrm1663
  4. Tada S, Blow JJ. 1998. The replication licensing system. Biol. Chem. 379: 941-949. https://doi.org/10.1515/bchm.1998.379.8-9.941
  5. Forsburg SL. 2004. Eukaryotic MCM proteins: beyond replication initiation. Microbiol. Mol. Biol. Rev. 68: 109-131. https://doi.org/10.1128/MMBR.68.1.109-131.2004
  6. Yu S, Wang G, Shi Y, Xu H, Zheng Y, Chen Y. 2020. MCMs in cancer: prognostic potential and mechanisms. Anal. Cell Pathol. (Amst). 2020: 3750294.
  7. Lau KM, Chan QK, Pang JC, Li KK, Yeung WW, Chung NY, et al. 2010. Minichromosome maintenance proteins 2, 3 and 7 in medulloblastoma: overexpression and involvement in regulation of cell migration and invasion. Oncogene 29: 5475-5489. https://doi.org/10.1038/onc.2010.287
  8. Zhang X, Teng Y, Yang F, Wang M, Hong X, Ye LG, et al. 2015. MCM2 is a therapeutic target of lovastatin in human non-small cell lung carcinomas. Oncol. Rep. 33: 2599-2605. https://doi.org/10.3892/or.2015.3822
  9. Liu Z, Li J, Chen J, Shan Q, Dai H, Xie H, et al. 2018. MCM family in HCC: MCM6 indicates adverse tumor features and poor outcomes and promotes S/G2 cell cycle progression. BMC Cancer 18: 200.
  10. Qiu YT, Wang WJ, Zhang B, Mei LL, Shi ZZ. 2017. MCM7 amplification and overexpression promote cell proliferation, colony formation and migration in esophageal squamous cell carcinoma by activating the AKT1/mTOR signaling pathway. Oncol. Rep. 37: 3590-3596. https://doi.org/10.3892/or.2017.5614
  11. Ishimi Y, Okayasu I, Kato C, Kwon HJ, Kimura H, Yamada K, et al. 2003. Enhanced expression of Mcm proteins in cancer cells derived from uterine cervix. Eur. J. Biochem. 270: 1089-1101. https://doi.org/10.1046/j.1432-1033.2003.03440.x
  12. Freeman A, Morris LS, Mills AD, Stoeber K, Laskey RA, Williams GH, et al. 1999. Minichromosome maintenance proteins as biological markers of dysplasia and malignancy. Clin. Cancer Res. 5: 2121-2132.
  13. Seo YS, Kang YH. 2018. The human replicative helicase, the CMG complex, as a target for anti-cancer therapy. Front. Mol. Biosci. 5: 26.
  14. Majid S, Dar AA, Saini S, Chen Y, Shahryari V, Liu J, et al. 2010. Regulation of minichromosome maintenance gene family by microRNA-1296 and genistein in prostate cancer. Cancer Res. 70: 2809-2818. https://doi.org/10.1158/0008-5472.CAN-09-4176
  15. Bruemmer D, Yin F, Liu J, Kiyono T, Fleck E, Van Herle A, et al. Atorvastatin inhibits expression of minichromosome maintenance proteins in vascular smooth muscle cells. Eur. J. Pharmacol. 462: 15-23.
  16. Kim SH, Kim SC, Ku JL. 2017. Metformin increases chemo-sensitivity via gene downregulation encoding DNA replication proteins in 5-Fu resistant colorectal cancer cells. Oncotarget 8: 56546-56557. https://doi.org/10.18632/oncotarget.17798
  17. Guan YB, Yang DR, Nong SJ, Ni J, Hu CH, Li J, et al. 2017. Breviscapine (BVP) inhibits prostate cancer progression through damaging DNA by minichromosome maintenance protein-7 (MCM-7) modulation. Biomed. Pharmacother. 93: 103-116. https://doi.org/10.1016/j.biopha.2017.06.024
  18. Ishimi Y, Sugiyama T, Nakaya R, Kanamori M, Kohno T, Enomoto T, et al. Effect of heliquinomycin on the activity of human minichromosome maintenance 4/6/7 helicase. FEBS J. 276: 3382-3391.
  19. Toyokawa G, Masuda K, Daigo Y, Cho HS, Yoshimatsu M, Takawa M, et al. 2011. Minichromosome maintenance protein 7 is a potential therapeutic target in human cancer and a novel prognostic marker of non-small cell lung cancer. Mol. Cancer 10: 65.
  20. Ali SH, Chandraker A, DeCaprio JA. 2007. Inhibition of Simian virus 40 large T antigen helicase activity by fluoroquinolones. Antivir. Ther. 12: 1-6.
  21. Simon N, Bochman ML, Seguin S, Brodsky JL, Seibel WL, Schwacha A. 2013. Ciprofloxacin is an inhibitor of the Mcm2-7 replicative helicase. Biosci. Rep. 33: e00072.
  22. Cragg GM, Newman DJ. 2005. Plants as a source of anti-cancer agents. J. Ethnopharmacol. 100: 72-79. https://doi.org/10.1016/j.jep.2005.05.011
  23. Pradhan D, Biswasroy P, Sahu A, Sahu DK, Ghosh G, Rath G. 2021. Recent advances in herbal nanomedicines for cancer treatment. Curr. Mol. Pharmacol. 14: 292-305. https://doi.org/10.2174/1874467213666200525010624
  24. Kwon HJ, Hong, YK, Park C, Choi YH, Yun HJ, Lee EW, et al. 2010. Widdrol induces cell cycle arrest, associated with MCM downregulation, in human colon adenocarcinoma cells. Cancer Lett. 290: 96-103. https://doi.org/10.1016/j.canlet.2009.09.003
  25. Kwon HJ, Lee EW, Hong YK, Yun HJ, Kim BW. 2010. Widdrol from Juniperus chinensis induces apoptosis in human colon adenocarcinoma HT29 cells. Biotechnol. Bioprocess Eng. 15: 167-172. https://doi.org/10.1007/s12257-009-0154-4
  26. Yun HJ, Hyun SK, Park JH, Kim BW, Kwon HJ. 2012. Widdrol activated DNA damage checkpoint through the signaling Chk2-p53-Cdc25A-p21-MCM4 pathway in HT29 cells. Mol. Cell Biochem. 363: 281-289. https://doi.org/10.1007/s11010-011-1180-z
  27. Sherr CJ. 2000. The Pezcoller lecture: cancer cell cycle revisited. Cancer Res. 60: 3689-3695.
  28. Nevins JR. 1998. Toward an understanding of the functional complexity of the E2F and retinoblastoma families. Cell Growth Differ. 9: 585-593.
  29. Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Hensen PM. 1992. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J. Immunol. 148: 2207-2216. https://doi.org/10.4049/jimmunol.148.7.2207
  30. Martin SJ, Reutelingsperger CP, McGahon AJ, Rader JA, van Schie RC, LaFace DM, et al. 1995. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J. Exp. Med. 182: 1545-1556. https://doi.org/10.1084/jem.182.5.1545
  31. Koopman G, Reutelingsperger, CP, Kuijten GA, Keehnen RJ, Pals ST, van Oers MH. 1994. Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood 84: 1415-1420. https://doi.org/10.1182/blood.V84.5.1415.bloodjournal8451415
  32. Chang CI, Chen WC, Shao YY, Yeh GR, Yang NS, Chiang W, et al. 2008. A new labdane-type diterpene from the bark of Juniperus chinensis Linn. Nat. Prod. Res. 22: 1158-1162. https://doi.org/10.1080/14786410601132444
  33. Guleria S, Kumar A, Tiku AK. 2008. Chemical composition and fungitoxic activity of essential oil of Thuja orientalis L. grown in the north-western Himalaya. Z Naturforsch. C, J. Biosci. 63: 211-214. https://doi.org/10.1515/znc-2008-3-409
  34. Bhatia SP, McGinty D, Letizia CS, Api AM. 2008. Fragrance material review on cedrol. Food Chem. Toxicol. 46: S100-S102.
  35. Dayawansa S, Umeno K, Takakura H, Hori E, Tabuchi E, Nagashima Y, et al. 2003. Autonomic responses during inhalation of natural fragrance of Cedrol in humans. Auton Neurosci. 108: 79-86. https://doi.org/10.1016/j.autneu.2003.08.002
  36. Umeno K, Hori E, Tsubota M, Shojaku H, Miwa T, Nagashima Y, et al. 2008. Effects of direct cedrol inhalation into the lower airway on autonomic nervous activity in totally laryngectomized subjects. Br. J. Clin. Pharmacol. 65: 188-196. https://doi.org/10.1111/j.1365-2125.2007.02992.x
  37. Yada Y, Sadachi H, Nagashima Y, Suzuki T. 2007. Overseas survey of the effect of cedrol on the autonomic nervous system in three countries. J. Physiol. Anthropol. 26: 349-354. https://doi.org/10.2114/jpa2.26.349
  38. Kagawa D, Jokura H, Ochiai R, Tokimitsu I, Tsubone H. 2003. The sedative effects and mechanism of action of cedrol inhalation with behavioral pharmacological evaluation. Planta Med. 69: 637-641. https://doi.org/10.1055/s-2003-41114
  39. Loizzo MR, Tundis R, Menichini F, Saab AM, Statti GA, Menichini F. 2008. Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cells. Cell Prolif. 41: 1002-1012. https://doi.org/10.1111/j.1365-2184.2008.00561.x
  40. Zhang SY, Li XB, Hou SG, Sun Y, Shi YR, Lin SS. 2016. Cedrol induces autophagy and apoptotic cell death in A549 non-small cell lung carcinoma cells through the PI3K/Akt signaling pathway, the loss of mitochondrial transmembrane potential and the generation of ROS. Int. J. Mol. Med. 38: 291-299. https://doi.org/10.3892/ijmm.2016.2585
  41. Chang KF, Huang XF, Chang JT, Huang YC, Weng JC, Tsai NM. 2020. Cedrol suppresses glioblastoma progression by triggering DNA damage and blocking nuclear translocation of the androgen receptor. Cancer Lett. 495: 180-190. https://doi.org/10.1016/j.canlet.2020.09.007
  42. Mishra SK, Bae YS, Lee YM, Kim JS, Oh SH, Kim HM. 2021. Sesquiterpene alcohol cedrol chemosensitizes human cancer cells and suppresses cell proliferation by destabilizing plasma membrane lipid rafts. Front. Cell Dev. Biol. 8: 571676.
  43. Cai L, Ye H, Li X, Lin Y, Yu F, Chen J, et al. 2013. Chemical constituents of volatile oil from Pyrolae herba and antiproliferative activity against SW1353 human chondrosarcoma cells. Int. J. Oncol. 42: 1452-1458. https://doi.org/10.3892/ijo.2013.1816
  44. Fulda S, Debatin KM. 2006. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25: 4798-4811. https://doi.org/10.1038/sj.onc.1209608
  45. McIlwain DR, Berger T, Mak TW. 2013. Caspase functions in cell death and disease. Cold Spring Harb Perspect. Biol. 5: a008656.
  46. Pfeffer CM, Singh ATK. 2018. Apoptosis: a target for anticancer therapy. Int. J. Mol. Sci. 19: 448.