Journal of Applied Biological Chemistry

  • Volume 66
  • /
  • Pages.272-281
  • /
  • 2023
  • /
  • 1976-0442(pISSN)
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  • 2234-7941(eISSN)
The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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Cytotoxic compounds against adenocarcinoma alveolar epithelial A549 cells from Paeoniae Radix

작약 뿌리에서 분리한 폐포 선암 세포주 A549에 대한 세포독성 화합물

  • Ji Won Park (Research Institute of Pharmaceutical Science, College of Pharmacy, Kyungpook National University) ;
  • Sang-Eun Shin (Research Institute of Pharmaceutical Science, College of Pharmacy, Kyungpook National University) ;
  • Haewon Park (Research Institute of Pharmaceutical Science, College of Pharmacy, Kyungpook National University) ;
  • Jeong Ah Kim (Research Institute of Pharmaceutical Science, College of Pharmacy, Kyungpook National University) ;
  • Eun-Ju Yang (College of Pharmacy, Chung-Ang University) ;
  • Kyung-Sik Song (Research Institute of Pharmaceutical Science, College of Pharmacy, Kyungpook National University)
  • Received : 2023.04.19
  • Accepted : 2023.06.27
  • Published : 2023.12.31
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Abstract

It has been known that Paeoniae Radix (PR) contains monoterpene glycosides showing a variety of biological activities such as anti-spasmodic, anti-inflammatory, anti-viral, neuroprotective, and sedative effects. This study aimed to find the cytotoxic compounds isolated from the dichloromethane (CH2Cl2)- and ethyl acetate-soluble fractions of PR. As results, thirteen compounds (1-13) were isolated and the chemical structures were identified. In addition, the human alveolar adenocarcinoma cell line (A549) was treated with isolated compounds to determine the cytotoxic effect via evaluation of cell viability. The reduction of A549 cell viability was shown as following order; gallic acid (8) > (2S)-naringenin (9) > methyl gallate (10)>6'-O-benzoylpaeoniflorin (7) > palmitic acid (3). Especially, 7 did not show the cytotoxicity in the human lung fibroblast cell line (MRC-5). The effect of 7 on the cell viabilities in A549 and MRC-5 is firstly reported in this study. Further study is required to find out the cytotoxic mechanism and the selectivity for the cancer cells of 7 in detail.

작약 뿌리는 monoterpene glycoside계 물질을 함유하고 있으며, 이들 화합물은 항경련, 항염증, 항바이러스, 신경보호 및 진정효과를 나타내는 것으로 알려져 있다. 이번 연구에서는 작약 뿌리의 dichloromethane (CH2Cl2) 및 ethyl acetate (EtOAc) 가용성 분획으로부터 세포독성 물질을 탐색하고자 하였다. 그 결과, 총 13종의 화합물을 분리할 수 있었으며, 이들의 세포독성 평가를 위해 사람 유래 폐암 선암 세포주인 A549에 처리하여 세포생존율 변화를 관찰하였다. A549에 대한 세포독성은 gallic acid (8) > (2S)-naringenin (9) > methyl gallate (10) > 6'-Obenzoylpaeoniflorin (7) > palmitic acid (3) 순으로 나타났다. 특히, 7은 normal cell인 MRC-5에 대한 독성은 없는 것으로 확인되었으며, 7의 A549 및 MRC-5 세포생존율에 미치는 영향에 대한 보고는 이번이 처음이다. 향후 7에 대한 세포독성 메커니즘 및 선택성과 관련된 추가연구가 필요할 것으로 판단된다.

Keywords

Acknowledgement

이 논문은 2022학년도 경북대학교 연구년 교수 연구비에 의하여 작성되었음. 중앙대학교에서 실시한 활성평가 연구는 농촌진흥청 연구사업(세부과제번호: PJ014208)의 지원에 의해 수행되었습니다.

References

  1. Causes of Death Statistics in 2021. Statistics Korea (2022) https://www.korea.kr/news/policyBriefingView.do?newsId=156527816 Accessed 27 Sep 2022
  2. Schabath MB, Cote ML (2019) Cancer progress and priorities: lung cancer. Cancer Epidemiol Biomark Prev 28: 1563-1579. doi: 10.1158/1055-9965.EPI-19-0221
  3. Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran Jr WJ, Wu Y-L, Paz-Ares L (2017) Lung cancer: current therapies and new targeted treatments. The Lancet 389: 299-311. doi: 10.1016/S0140-6736(16)30958-8
  4. Jones GS, Baldwin DR (2018) Recent advances in the management of lung cancer. Clin Med 18: s41. doi: 10.7861/clinmedicine.18-2s-s41
  5. Li Z, Feiyue Z, Gaofeng L (2021) Traditional Chinese medicine and lung cancer--From theory to practice. Biomed Pharmacother 137: 111381. doi: 10.1016/j.biopha.2021.111381
  6. Kim SJ, Park JH, Choi SY, Son KH, Kim KU (2007) Isolated and identification of biological activity compounds from leaves and stem of Paeonia lactiflora Pallas. Korean J Medicinal Crop Sci 15: 6-11
  7. Won JB, Ma JY, Lee JH, Ma CJ (2009) Simultaneous quantification of three marker compounds in Samultang by HPLC/DAD. Korean J Pharmacogn 40: 298-302
  8. Tan YQ, Chen HW, Li J, Wu QJ (2020) Efficacy, chemical constituents, and pharmacological actions of Radix Paeoniae Rubra and Radix Paeoniae Alba. Front Pharmacol 11: 1054. doi: 10.3389/fphar.2020.01054
  9. The Korean Pharmacopoeia (2022) Ministry of Food and Drug Safety (KFDA), Cheongju
  10. Herbst RS, Heymach JV, Lippman S (2008) Molecular origins of cancer: Lung cancer. N Engl J Med 359: 1367-1380. doi: 10.1056/NEJMra0802714
  11. Zhou P, Hu J, Wang X, Wang J, Zhang Y, Wang C (2018) Epidermal growth factor receptor expression affects proliferation and apoptosis in non-small cell lung cancer cells via the extracellular signal-regulated kinase/microRNA 200a signaling pathway. Oncol Lett 15: 5201-5207. doi: 10.3892/ol.2018.7961
  12. Rho JK, Choi YJ, Lee JK, Ryoo B-Y, Yang SH, Kim CH, Lee JC (2009) Epithelial to mesenchymal transition derived from repeated exposure to gefitinib determines the sensitivity to EGFR inhibitors in A549, a non-small cell lung cancer cell line. Lung Cancer 63: 219-226. doi: 10.1016/ j.lungcan.2008.05.017
  13. Tong N, Zhang J, Chen Y, Li Z, Luo Y, Zuo H, Zhao X (2012) Berberine sensitizes mutliple human cancer cells to the anticancer effects of doxorubicin in vitro. Oncol Lett 3: 1263-1267. doi: 10.3892/ol.2012.644
  14. Park YH, Lim SH, Ham HJ, Kim HY, Jeong HN, Kim KH, Kim SM (2010) Isolation of anti-inflammatory active substance β-sitosterol from seabuckthorn (Hippophae rhamnoides L.) stem. J Korean Soc Food Sci Nutr 39: 980-985
  15. Paliany AS, Sivasothy Y, Awang K, Rizman-Idid M, Alias SA (2014) Marine derived fungi of peninsular Malaysia-A biochemical perspective. Chiang Mai J Sci 41: 894-909
  16. Abdullah BM, Zubairi SI, Huri HZ, Hairunisa N, Yousif E, Basu RC (2016) Polyesters based on linoleic acid for biolubricant basestocks: Low-temperature, Tribological and Rheological properties. Plos One 11: e0151603. doi: 10.1371/journal.pone.0151603
  17. Tlhapi DB, Ramaite ID, Anokwuru CP (2021) Metabolomic profiling and antioxidant activities of Breonadia salicina using 1H-NMR and UPLC-QTOF-MS analysis. Molecules 26: 6707. doi: 10.3390/molecules26216707
  18. Samy MN, Mahmoud BK, Shady NH, Abdelmohsen UR, Ross SA (2022) Bioassay-guided fractionation with antimalarial and antimicrobial activities of Paeonia officinalis. Molecules 27: 8382. doi: 10.3390/molecules27238382
  19. Yean MH, Lee JY, Kim JS, Kang SS (2008) Phytochemical studies on Paeoniae Radix (1); Monoterpene glucosides. Korean J Pharmacogn 39: 19-27
  20. Yen PH, Van Kiem P, Nhiem NX, Tung NH, Quang TH, Van Minh C, Kim JW, Choi EM, Kim YH (2007) A new monoterpene glycoside from the roots of Paeonia lacti-flora increases the differentiation of osteoblastic MC3T3-E1 cells. Arch Pharm Res 30: 1179-1185. doi: 10.1007/BF02980258
  21. Chu BY, Jin WY, Choi SL, Myung PK, Seong YH, Song KS, Bae KH (2004) A Cytotoxic Compound from Moutan Cortex Radicis. Korean J Medicinal Crop Sci 12: 255-261
  22. Kwon OK, Kim CS, Suh WS, Park KJ, Cha JM, Choi SU, Kwon HC, Lee KR (2016) Phenolic compounds from the twigs of Corylopsis coreana Uyeki and their cytotoxic activity. Korean J Pharmacogn 47: 1-6
  23. Kim JG, Le TPL, Hong HR, Han JS, Ko JH, Lee SH, Lee MK, Hwang BY (2019) Nitric oxide inhibitory constituents from the fruits of Amomum tsao-ko. Nat Prod Sci 25: 76-80
  24. Oh JY, Choi U, Kim YS, Shin DH (2003) Isolation and identification of antioxidative components from bark of Rhus javanica Linne. Korean J Food Sci Technol 35: 726-732
  25. Orabi MA, Zidan SA, Attia GH, Alyami HS, Matsunami K, Hatano T (2021) Ellagitannins and simple phenolics from the halophytic plant Tamarix nilotica. Nat Prod Res 36: 177-185. doi: 10.1080/14786419.2020.1774757
  26. Zhang FY, Du GJ, Zhang L, Zhang CL, Lu WL, Liang W (2009) Naringenin enhances the anti-tumor effect of doxorubicin through selectively inhibiting the activity of multidrug resistance-associated proteins but not P-glycoprotein. Pharm Res 26: 914-925. doi: 10.1007/s11095-008-9793-y
  27. Lee ER, Kang YJ, Choi HY, Kang GH, Kim JH, Kim BW, Han YS, Nah SY, Paik HD, Park YS (2007) Induction of apoptotic cell death by synthetic naringenin derivatives in human lung epithelial carcinoma A549 cells. Biol Pharm Bull 30: 2394-2398. doi: 10.1248/bpb.30.2394
  28. Sandeep K, Won Bong L, Ji Sun K, Sang Woo K, Hui Z, Kum Hue B, Min Sung C, Hee Kyun O, Ok Su K, Hong Ran C (2012) C16 Saturated fatty acid induced autophagy in A549 cells through topoisomerase I inhibition. Food Nutr Sci 2012: doi: 10.4236/fns.2012.39160
  29. Kim C, Sim H, Bae JS (2022) Benzoylpaeoniflorin activates anti-inflammatory mechanisms to mitigate sepsis in cell-culture and mouse sepsis models. Int J Mol Sci 23: 13130. doi: 10.3390/ijms232113130
  30. Zhu X, Fang ZH (2014) New monoterpene glycosides from the root cortex of Paeonia suffruticosa and their potential anti-inflammatory activity. Nat Prod Res 28: 301-305. doi: 10.1080/14786419.2013.858340
  31. Kim SH, Lee MK, Lee KY, Sung SH, Kim J, Kim YC (2009) Chemical constituents isolated from Paeonia lactiflora roots and their neuroprotective activity against oxidative stress in vitro. J Enzym Inhib Med Chem 24: 1138-1140. doi: 10.1080/14756360802667977