Anticancer Effect of Paedoksans for Oral Squamous Cell Carcinoma and Malignant Pleural Mesothelioma

패독산류의 구강편평세포암종 및 악성중피종에 대한 항암 활성

  • Oh, Ha-Na (College of Pharmacy and Natural Medicine Research Institute, Mokpo National University) ;
  • Kim, Hyun-Jung (College of Pharmacy and Natural Medicine Research Institute, Mokpo National University) ;
  • Chae, Jung-Il (Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 Plus, Chonbuk National University) ;
  • Shim, Jung-Hyun (College of Pharmacy and Natural Medicine Research Institute, Mokpo National University) ;
  • Yoon, Goo (College of Pharmacy and Natural Medicine Research Institute, Mokpo National University)
  • 오하나 (목포대학교 약학대학 천연약물연구소) ;
  • 김현정 (목포대학교 약학대학 천연약물연구소) ;
  • 채정일 (전북대학교 치의학대학원 치과약리학교실(BK21 플러스사업단)) ;
  • 심정현 (목포대학교 약학대학 천연약물연구소) ;
  • 윤구 (목포대학교 약학대학 천연약물연구소)
  • Received : 2017.09.05
  • Accepted : 2017.09.20
  • Published : 2017.09.30

Abstract

In order to search for anticancer agent as therapy of oral squamous cell carcinoma (OSCC) and malignant pleural mesothelioma (MPM) from Korean traditional prescriptions, we selected 58 traditional prescriptions based on a review of the Korean traditional medicine books. Among the selected traditional prescriptions, only water extracts of paedoksan (敗毒散) showed relatively good cytotoxicity at the concentration of $50{\mu}g/ml$. Additionally, we evaluated cytotoxicity for various paedoksans and each herbal ingredient in paedoksans. The root of Anthriscus sylvestris exhibited more cytotoxic effect than any other ingredients in paedoksans. Bioactivity-guided fractionation of the MC layer of Anthriscus sylvestris led to the isolation of deoxypodophyllotoxin (DPT). DPT exhibited dose-dependently significant cytotoxicity against OSCC and MPM cell with nM range. Therefore, DPT from A. sylvestris might be a potential candidate as an effective anticancer therapeutic agent for OSCC and MPM.

Keywords

References

  1. Chae, J. I. and Shim, J. H. (2012) Apoptotic effect of mithramycin A via regulation of specificity protein 1 expression in oral squamous cancer cells. Cancer Prev. Res. 17: 212-217.
  2. Tsao, A. S., Wistuba, I., Roth, J. A. and Kindler, H. L. (2009) Malignant pleural mesothelioma. J. Clin. Oncol. 27: 2081-2090. https://doi.org/10.1200/JCO.2008.19.8523
  3. Boutin, C., Schlesser, M., Frenay, C. and Astoul, P. (1998) Malignant pleural mesothelioma. Eur. Respir. J. 12: 972-981. https://doi.org/10.1183/09031936.98.12040972
  4. Tomek, S., Emri, S., Krejcy, K. and Manegold, C. (2003) Chemotherapy for malignant pleural mesothelioma: past results and recent developments. Br. J. Cancer 88: 167-174. https://doi.org/10.1038/sj.bjc.6600673
  5. Kim, K. H., Yoon, G., Cho, J. J., Cho, J. H., Cho, Y. S., Chae, J. I. and Shim, J. H. (2015) Licochalcone A induces apoptosis in malignant pleural mesothelioma through downregulation of Sp1 and subsequent activation of mitochondria-related apoptotic pathway. Int. J. Oncol. 46: 1385-1392. https://doi.org/10.3892/ijo.2015.2839
  6. Lee, Y. H., Kim, Y. G. and Kim, J. H. (2000) Studies on anti-oral cancer activities of medicinal plant extracts. J. Korean Assoc. Oral and Maxillofac. Surg. 26: 53-58.
  7. Lee, W., Kim, H. J., Moon, H. S., Kim, S. N. and Yoon, G. (2013) Screening of Korean traditional prescriptions with inhibitory activity against protein tyrosine phosphatase 1B and analysis of Jakgamhwangsinbu-tang (芍甘黃辛附湯) prescription. Kor. J. Pharmacogn. 44: 176-181.
  8. Im, G. Y., Hwang, Y. H., Lee, J. H., Oh, Y. C., Cho, W. K. and Ma, J. Y. (2011) Acute toxicity study on Insampaedok-san and fermented Insampaedok-san. Kor. J. Oriental Preventive Medical Society 15: 141-152.
  9. Kang, T. J., Lee, S. Y., Singh R. P., Agarwak R. and Yim, D. S. (2009) Anti-tumor activity of oxypeucedanin from Ostericum koreanum against human prostate carcinoma DU145 cells. Acta Oncologica 48: 895-900. https://doi.org/10.1080/02841860902824925
  10. Li, W., Tian, Y. H., Liu, Y., Wang, Z., Tang, S., Zhang, J. and Wang, Y. P. (2016) Platycodin D exerts anti-tumor efficacy in H22 tumor-bearing mice via improving immune function and inducing apoptosis. J. Toxicol. Sci. 41: 417-428. https://doi.org/10.2131/jts.41.417
  11. Liu, R. Y. and Li, J. P. (2014) Saikosaponin-d inhibits proliferation of human undifferentiated thyroid carcinoma cells through induction of apoptosis and cell cycle arrest. Eur. Rev. Med. Pharmacol. Sci. 18: 2435-2443.
  12. Wang, Y. R., Xu, Y., Jiang, Z. Z., Guerram, M., Wang, B., Zhu, X. and Zhang, L. Y. (2015) Deoxypodophyllotoxin induces G2/M cell cycle arrest and apoptosis in SGC-7901 cells and inhibits tumor growth in vivo. Molecules 20: 1661-1675. https://doi.org/10.3390/molecules20011661
  13. Bae, K. E., Coi, Y. W., Kim, S. T. and Kim, Y. K. (2011) Components of Rhizome extract of Cnidium officinale Makino and their In vitro biological effects. Molecules 16: 8833-8847. https://doi.org/10.3390/molecules16108833
  14. Oh, H. L., Lee, D. K., Lim, H. and Lee, C. H. (2010) HY253, a novel decahydrofluorene analog, from Aralia continentalis, induces cell cycle arrest at the G1 phase and cytochrome cmediated apoptosis in human lung cancer A549 cells. J. Ethnopharmacol. 129: 135-139. https://doi.org/10.1016/j.jep.2010.02.010
  15. Oh, H. L. and Lee, C. H. (2010) HY251, a novel decahydrocyclopenta[a]indene analog, from Aralia continentalis induces apoptosis via down-regulation of AR expression in human prostate cancer LNCaP cells. Bioorg. Med. Chem. Lett. 21: 1347-1349.
  16. Kim, H. S., Lim, J. M., Kim, J. Y., Kim, Y., Park, S. and Sohn, J. (2016) Panaxydol, a component of Panax ginseng, induces apoptosis in cancer cells through EGFR activation and ER stress and inhibits tumor growth in mouse models. Int. J. Cancer 138: 1432-1441. https://doi.org/10.1002/ijc.29879
  17. Yoon, G., Jung, Y. D. and Cheon, S. H. (2005) Cytotoxic Allyl Retrochalcone from the Roots of Glycyrrhiza inflata. Chem. Pharm. Bull. 53: 694-695. https://doi.org/10.1248/cpb.53.694
  18. Ma, J., Liu, J., Lu, C. and Cai, D. (2015) Pachymic acid induces apoptosis via activating ROS-dependent JNK and ER stress pathways in lung cancer cells. Cancer Cell. Int. 15: 78. https://doi.org/10.1186/s12935-015-0230-0
  19. Han, K., Meng, W., Zhang, J. J., Zhou, Y., Wang, Y. L., Su, Y., Lin, S. C., Gan, Z. H., Sun, Y. N. and Min, D. L. (2016) Luteolin inhibited proliferation and induced apoptosis of prostate cancer cells through miR-301. Onco. Targets Ther. 9: 3085-3094.
  20. Venkatesan, T., Jeong, M. J., Choi, Y. W., Park, E. J., El-Desouky, S. K. and Kim, Y. K. (2016) Deoxyrhapontigenin, a natural stilbene derivative isolated from Rheum undulatum L. induces endoplasmic reticulum stress-mediated apoptosis in human breast cancer cells. Integr. Cancer Ther. 15: NP44-NP52. https://doi.org/10.1177/1534735416636958
  21. Kang, T. H., Bang, J. Y., Kim, M. H., Kang, I. C., Kim, H. M. and Jeong, H. J. (2011) Atractylenolide III, a sesquiterpenoid, induces apoptosis in human lung carcinoma A549 cells via mitochondria-mediated death pathway. Food Chem. Toxicol. 49: 514-519. https://doi.org/10.1016/j.fct.2010.11.038
  22. 생약학교재 편찬위원회 (2006) 생약학, 200, 동명사, 서울.
  23. Kim, J. H., Hyun, J. W. and Kim, Y. G. (1999) Anticancer effects of natural medicinal plant extracts on oral carcinoma cells. J. Appl. Pharmacol. 7: 153-157.
  24. Favoni, R. E., Daga, A., Malatesta, P. and Florio, T. (2012) Preclinical studies identify novel targeted pharmacological strategies for treatment of human malignant pleural mesothelioma. Br. J. Pharmacol. 166: 532-553. https://doi.org/10.1111/j.1476-5381.2012.01873.x
  25. Lin, C. X., Son, M. J., Ju, H. K., Moon, T. C., Lee, E., Kim, S. H., Kim, M. J., Son, J. K., Lee, S. H. and Chang, H. W. (2004) Deoxypodophyllotoxin, a naturally occurring lignan, inhibits the passive cutaneous anaphylaxis reaction. Planta Med. 70: 474-476. https://doi.org/10.1055/s-2004-818981
  26. Kim, K. Y., Cho, H. J., Yu, S. N., Kim, S. H , Yu, H. S., Park, Y. M., Mirkheshti, N., Kim, S. Y., Song, C. S., Chatterjee, B. and Ahn, S. C. (2013) Interplay of reactive oxygen species, intracellular Ca2+ and mitochondrial homeostasis in the apoptosis of prostate cancer cells by deoxypodophyllotoxin. J. Cell Biochem. 114: 1124-34. https://doi.org/10.1002/jcb.24455
  27. Shin, S. Y., Yong, Y., Kim, C. G., Lee, Y. H. and Lim, Y. (2010) Deoxypodophyllotoxin induces G2/M cell cycle arrest and apoptosis in HeLa cells. Cancer Lett. 287: 231-239. https://doi.org/10.1016/j.canlet.2009.06.019
  28. Jeong, G. S., Kwon, O. K., Park, B. Y., Oh, S. R., Ahn, K. S., Chang, M. J., Oh, W. K., Kim, J. C., Min, B. S., Kim, Y. C. and Lee, H. K. (2007) Lignans and coumarins from the roots of Anthriscus sylvestris and their increase of caspase-3 activity in HL-60 cells. Biol. Pharm. Bull. 30: 1340-1343. https://doi.org/10.1248/bpb.30.1340