Natural Product Sciences

The Korean Society of Pharmacognosy (한국생약학회)
권호 표지
DOI QR코드

DOI QR Code

The Cytotoxic Constituents of Betula platyphylla and their Effects on Human Lung A549 Cancer Cells

  • Yang, Eun-Ju (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University) ;
  • An, Ju-Hee (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University) ;
  • Son, Youn Kyoung (Biological and Genetic Resources Assessment Division, National Institute of Biological Resources) ;
  • Yeo, Joo-Hong (Biological and Genetic Resources Assessment Division, National Institute of Biological Resources) ;
  • Song, Kyung-Sik (Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University)
  • Received : 2018.05.09
  • Accepted : 2018.08.24
  • Published : 2018.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

During the screening for cytotoxic compounds from plants grown in Korea, Betula platyphylla (BP) showed potent activity against the adenocarcinomic human alveolar basal epithelial A549 cell line. To identify the cytotoxic components from BP, the $CH_2Cl_2$ fraction with the most significant cytotoxic effect was applied to the column chromatographies. Seven compounds were isolated: lupeol (1), betulinic acid (2), (-)-rhododendrol (3), platyphyllenone (4), platyphyllone (5), (-)-centrolobol (6), and oleanolic acid (7). Among them, three diarylheptanoids (4 - 6) exhibited cytotoxicity toward A549 cells. Especially, $50{\mu}M$ of 4 reduced A549 cell viability to $18.93{\pm}0.82%$ compared to control ($100.00{\pm}21.48%$). Lactate dehydrogenase (LDH) leakage and intracellular reactive oxygen species (ROS) production were also induced by $50{\mu}M$ 4. This is the first report on the cytotoxic effect of BP-derived diarylheptanoids 4-6 against A549 cells. The compound 4 may be useful for the development of early hit compounds for non-small cell lung carcinoma, but the consideration about selectivity of 4 is required since 4 also showed the cytotoxicity in the human normal lung epithelial BEAS-2B cell line.

Keywords

References

  1. Zhu, Q. G.; Zhang, S. M.; Ding, X. X.; He, B.; Zhang, H. Q. Oncotarget 2017, 8, 57680-57692.
  2. Dong, L.; Lei, D.; Zhang, H. Oncotarget 2017, 8, 64600-64606.
  3. Wang, J.; Chen, J.; Guo, Y.; Wang, B.; Chu, H. Oncotarget 2017, 8, 53854-53872.
  4. Siegel, R. L.; Miller, K. D.; Jemal, A. CA Cancer J. Clin. 2016, 66, 7-30. https://doi.org/10.3322/caac.21332
  5. Zarogoulidis, K.; Zarogoulidis, P.; Darwiche, K.; Boutsikou, E.; Machairiotis, N.; Tsakiridis, K.; Katsikogiannis, N.; Kougioumtzi, I.; Karapantzos, I.; Huang, H.; Spyratos, D. J. Thorac. Dis. 2013, 5(S4), S389-S396.
  6. Kroschinsky, F.; Stolzel, F.; von Bonin, S.; Beutel, G.; Kochanek, M.; Kiehl, M.; Schellongowski, P. Crit. Care 2017, 21, 89. https://doi.org/10.1186/s13054-017-1678-1
  7. Daga, A.; Ansari, A.; Patel, S.; Mirza, S.; Rawal, R.; Umrania, V. Asian Pac. J. Cancer Prev. 2015, 16, 4147-4156. https://doi.org/10.7314/APJCP.2015.16.10.4147
  8. Ancuceanu, R. V.; Istudor, V. Altern. Med. Rev. 2004, 9, 402-419.
  9. Atanasov, A. G.; Waltenberger, B.; Pferschy-Wenzig, E. M.; Linder, T.; Wawrosch, C.; Uhrin, P.; Temml, V.; Wang, L.; Schwaiger, S.; Heiss, E. H.; Rollinger, J. M.; Schuster, D.; Breuss, J. M.; Bochkov, V.; Mihovilovic, M. D.; Kopp, B.; Bauer, R.; Dirsch, V. M.; Stuppner, H. Biotechnol. Adv. 2015, 33, 1582-1614. https://doi.org/10.1016/j.biotechadv.2015.08.001
  10. Schelman, W. R.; Mohammed, T. A.; Traynor, A. M.; Kolesar, J. M.; Marnocha, R. M.; Eickhoff, J.; Keppen, M.; Alberti, D. B.; Wilding, G.; Takebe, N.; Liu, G. Invest. New Drugs 2014, 32, 295-302. https://doi.org/10.1007/s10637-013-9999-7
  11. Baggstrom, M. Q.; Qi, Y.; Koczywas, M.; Argiris, A.; Johnson, E. A.; Millward, M. J.; Murphy, S. C.; Erlichman, C.; Rudin, C. M.; Govindan, R. J. Thorac. Oncol. 2011, 6, 1757-1760. https://doi.org/10.1097/JTO.0b013e31822e2941
  12. Ready, N.; Karaseva, N. A.; Orlov, S. V.; Luft, A. V.; Popovych, O.; Holmlund, J. T.; Wood, B. A.; Leopold, L. J. Thorac. Oncol. 2011, 6, 781-785. https://doi.org/10.1097/JTO.0b013e31820a0ea6
  13. Eom, H. J.; Kang, H. R.; Choi, S. U.; Kim, K. H. Chem. Biodivers. 2017, 14.
  14. Jiang, H.; Shen, Y.; Yasuda, E.; Chiba, M.; Terazawa, M. Eurasian J. For. Res. 2001, 3, 49-54.
  15. Wang, S. J.; Pei, Y. H.; Hua, H. M. J. Asian Nat. Prod. Res. 2001, 3, 157-160. https://doi.org/10.1080/10286020108041384
  16. Cho, N.; Kim, H. W.; Lee, H. K.; Jeon, B. J.; Sung, S. H. Biosci. Biotechnol. Biochem. 2016, 80, 166-171. https://doi.org/10.1080/09168451.2015.1072460
  17. Eom, H. J.; Kang, H. R.; Kim, H. K.; Jung, E. B.; Park, H. B.; Kang, K. S.; Kim, K. H. Bioorg. Chem. 2016, 66, 97-101. https://doi.org/10.1016/j.bioorg.2016.04.001
  18. Matsuda, H.; Ishikado, A.; Nishida, N.; Ninomiya, K.; Fujiwara, H.; Kobayashi, Y.; Yoshikawa, M. Bioorg. Med. Chem. Lett. 1998, 8, 2939-2944. https://doi.org/10.1016/S0960-894X(98)00528-9
  19. Lee, M.; Park, J. H.; Min, D. S.; Yoo, H.; Park, J. H.; Kim, Y. C.; Sung, S. H. Biosci. Biotechnol. Biochem. 2012, 76, 1616-1620. https://doi.org/10.1271/bbb.110887
  20. Lee, M.; Sung, S. H. Pharmacogn. Mag. 2016, 12, 276-281.
  21. Le, C. F.; Kailaivasan, T. H.; Chow, S. C.; Abdullah, Z.; Ling, S. K.; Fang, C. M. Int. Immunopharmacol. 2017, 44, 203-210. https://doi.org/10.1016/j.intimp.2017.01.013
  22. Prachayasittikul, S.; Saraban, P.; Cherdtrakulkiat, R.; Ruchirawat, S.; Prachayasittikul, V. EXCLI J. 2010, 9, 1-10.
  23. Kim, J. H.; Byun, J. C.; Bandi, A. K. R.; Hyun, C. G.; Lee, N. H. J. Med. Plants Res. 2009, 3, 914-920.
  24. Kim, M. H.; Nugroho, A.; Choi, J.; Park, J. H.; Park, H. J. Arch. Pharm. Res. 2011, 34, 971-978. https://doi.org/10.1007/s12272-011-0614-1
  25. Parmar, V. S.; Vardhan, A.; Taneja, P.; Sinha, R.; Patnaik, G. K.; Tripathi, S. C.; Boll, P. M.; Larsen, S. J. Chem. Soc. Perkin Trans. 1 1991, 11, 2687-2690.
  26. Ibrahim, S. R.; Fouad, M. A.; Abdel-Lateff, A.; Okino, T.; Mohamed, G. A. Nat. Prod. Res. 2014, 28, 1765-1771. https://doi.org/10.1080/14786419.2014.947489
  27. Sunnerheim-Sjoberg, K.; Knutsson, P. G. J. Chem. Ecol. 1995, 21, 1339-1348. https://doi.org/10.1007/BF02027566
  28. Ohta, S.; Koyama, M.; Aoki, T.; Suga, T. Bull. Chem. Soc. Jpn. 1985, 58, 2423-2424. https://doi.org/10.1246/bcsj.58.2423
  29. Onoja, E.; Ndukwe, I. G. J. Nat. Prod. Plant Resour. 2013, 3, 57-60.
  30. Awan, Z. I.; Habib-ur-Rehman, K. A. Y.; Minhas, F. A. IOSR J. App. Chem. 2013, 5, 58-66. https://doi.org/10.9790/5736-0545866
  31. Fuchino, H.; Konishi, S.; Satoh, T.; Yagi, A.; Saitsu, K.; Tatsumi, T.; Tanaka, N. Chem. Pharm. Bull. 1996, 44, 1033-1038. https://doi.org/10.1248/cpb.44.1033
  32. Terazawa, M.; Koga, T.; Okuyama, H.; Miyake, M. Jap. Wood Res. Soc. J. 1973, 19, 47-48.
  33. Kim, S. H.; Park, J. H.; Kim, T. B.; Lee, H. H.; Lee, K. Y.; Kim, Y. C.; Sung, S. H. Bioorg. Med. Chem. Lett. 2010, 20, 2824-2827. https://doi.org/10.1016/j.bmcl.2010.03.053
  34. Liao, C. R.; Kuo, Y. H.; Ho, Y. L.; Wang, C. Y.; Yang, C. S.; Lin, C. W.; Chang, Y. S. Molecules 2014, 19, 9515-9534. https://doi.org/10.3390/molecules19079515
  35. You, Y. J.; Nam, N. H.; Kim, Y.; Bae, K. H.; Ahn, B. Z. Phytother. Res. 2003, 17, 341-344. https://doi.org/10.1002/ptr.1140
  36. Rao, S. D.; Rao, B. N.; Devi, P. U.; Rao, A. K. Orient. J. Chem. 2017, 33, 173-180. https://doi.org/10.13005/ojc/330119
  37. Jang, G. U.; Choi, S. U.; Lee, K. R. Yakhak Hoeji 2005, 49, 244-248.
  38. Sidova, V.; Zoufaly, P.; Pokorny, J.; Dzubak, P.; Hajduch, M.; Popa, I.; Urban, M. PLoS One 2017, 12, e0171621. https://doi.org/10.1371/journal.pone.0171621
  39. Dinic, J.; Novakovic, M.; Podolski-Renic, A.; Vajs, V.; Tesevic, V.; Isakovi , A.; Pesic, M. Chem. Biol. Interact. 2016, 249, 36-45. https://doi.org/10.1016/j.cbi.2016.02.019
  40. Chokchaisiri, R.; Pimkaew, P.; Piyachaturawat, P.; Chalermglin, R.; Suksamrarn, A. Rec. Nat. Prod. 2014, 8, 46-50.
  41. Tsao, S. M.; Yin, M. C. J. Agric. Food Chem. 2015, 63, 3196-3204. https://doi.org/10.1021/acs.jafc.5b00102
  42. Dong, G. Z.; Jeong, J. H.; Lee, Y. I.; Lee, S. Y.; Zhao, H. Y.; Jeon, R.; Lee, H. J.; Ryu, J. H. Arch. Pharm. Res. 2017, 40, 509-517. https://doi.org/10.1007/s12272-017-0905-2
  43. Tung, N. H.; Kwon, H. J.; Kim, J. H.; Ra, J. C.; Ding, Y.; Kim, J. A.; Kim, Y. H. Bioorg. Med. Chem. Lett. 2010, 20, 1000-1003. https://doi.org/10.1016/j.bmcl.2009.12.057
  44. Ilic-Tomic, T.; Sokovic, M.; Vojnovic, S.; Ciric, A.; Veljic, M.; Nikodinovic-Runic, J.; Novakovic, M. Planta Med. 2017, 83, 117-125.
  45. Park, D.; Kim, H. J.; Jung, S. Y.; Yook, C. S.; Jin, C.; Lee, Y. S. Chem. Pharm. Bull. 2010, 58, 238-241. https://doi.org/10.1248/cpb.58.238
  46. Yadav, D.; Singh, S. C.; Verma, R. K.; Saxena, K.; Verma, R.; Murthy, P. K.; Gupta, M. M. Phytomedicine 2013, 20, 124-132. https://doi.org/10.1016/j.phymed.2012.10.017
  47. Novakovic, M.; Novakovic, I.; Cvetkovic, M.; Sladic, D.; Tesevic, V. Braz. J. Bot. 2015, 38, 441-446. https://doi.org/10.1007/s40415-015-0151-0
  48. Novakovic, M.; Pesic, M.; Trifunovic, S.; Vuckovic, I.; Todorovic, N.; Podolski-Renic, A.; Dinic, J.; Stojkovic, S.; Tesevic, V.; Vajs, V.; Milosavljevic, S. Phytochemistry 2014, 97, 46-54. https://doi.org/10.1016/j.phytochem.2013.11.001

Cited by

  1. Betulinic Acid Suppresses Ovarian Cancer Cell Proliferation through Induction of Apoptosis vol.9, pp.7, 2018, https://doi.org/10.3390/biom9070257
  2. The Inhibitory Effect of Cordycepin on the Proliferation of MCF-7 Breast Cancer Cells, and Its Mechanism: An Investigation Using Network Pharmacology-Based Analysis vol.9, pp.9, 2018, https://doi.org/10.3390/biom9090414
  3. 1,7‐Bis(4‐hydroxyphenyl)‐4‐hepten‐3‐one from Betula platyphylla induces apoptosis by suppressing autophagy flux and activating the p38 pathway in lung cancer cells vol.34, pp.1, 2018, https://doi.org/10.1002/ptr.6506
  4. Analysis and Identification of Active Compounds from Salviae miltiorrhizae Radix Toxic to HCT-116 Human Colon Cancer Cells vol.10, pp.4, 2018, https://doi.org/10.3390/app10041304
  5. Activation of JNK and p38 in MCF-7 Cells and the In Vitro Anticancer Activity of Alnus hirsuta Extract vol.25, pp.5, 2018, https://doi.org/10.3390/molecules25051073
  6. Regioselective Hydroxylation of Rhododendrol by CYP102A1 and Tyrosinase vol.10, pp.10, 2018, https://doi.org/10.3390/catal10101114
  7. Bioactivity-based analysis and chemical characterization of cytotoxic compounds from a poisonous mushroom, Amanita spissacea, in human lung cancer cells in vitro vol.35, pp.4, 2018, https://doi.org/10.1080/14786419.2019.1586699