Advertisement

Journal of Natural Medicines

, Volume 72, Issue 3, pp 615–625 | Cite as

A bibenzyl from Dendrobium ellipsophyllum induces apoptosis in human lung cancer cells

  • Anirut Hlosrichok
  • Somruethai Sumkhemthong
  • Boonchoo Sritularak
  • Pithi Chanvorachote
  • Chatchai ChaothamEmail author
Original Paper

Abstract

Failure of current chemotherapeutic drugs leads to the recurrence of tumor pathology and mortality in lung cancer patients. This study aimed to evaluate the anticancer activity and related mechanisms of 4,5,4′-trihydroxy-3,3′-dimethoxybibenzyl (TDB), a bibenzyl extracted from Dendrobium ellipsophyllum Tang and Wang, in human lung cancer cells. Cytotoxicity of TDB (0–300 µM) in different types of human lung cancer cells (H460, H292 and H23) and human dermal papilla cells (DPCs) was evaluated via MTT viability assay. Selective anticancer activity of TDB against human lung cancer cells was demonstrated with a high IC50 (approximately > 300 µM) in DPCs, while IC50 in human lung cancer H460, H292 and H23 cells was approximately 100 ± 5.18, 100 ± 8.73 and 188.89 ± 8.30 µM, respectively. After treatment with 50 µM of TDB for 24 h, flow cytometry analysis revealed the significant increase of early and late apoptosis with absence of necrosis cell death in human lung cancer cells. The up-regulation of p53, a tumor-suppressor protein, was elucidated in human lung cancer cells treated with 10–50 µM of TDB. Alteration to down-stream signaling of p53 including activation of pro-apoptosis protein (Bcl-2-associated X protein; Bax), reduction of anti-apoptosis (B cell lymphoma 2; Bcl-2 and myeloid cell leukemia 1; Mcl-1) and suppression on protein kinase B (Akt) survival pathway were notified in TDB-treated lung cancer cells. The information obtained from this study strengthens the potential development of TDB as an anticancer compound with a favorable human safety profile and high efficacy.

Keywords

Selective anticancer Apoptosis Dendrobium ellipsophyllum Bibenzyl Lung cancer p53 

Notes

Funding

The work was supported by a Research Grant for New Scholar Ratchadaphiseksomphot Endowment Fund Chulalongkorn University. AH would like to thank scholarship of 60/40 Support for Tuition Fee from the Graduate School, Chulalongkorn University.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Esposito L, Conti D, Ailavajhala R, Khalil N, Giordano A (2010) Lung cancer: are we up to the challenge? Curr Genomics 11:513–518.  https://doi.org/10.2174/138920210793175903 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Lin JJ, Cardarella S, Lydon CA, Dahlberg SE, Jackman DM, Jänne PA, Johnson BE (2016) Five-year survival in EGFR-mutant metastatic lung adenocarcinoma treated with EGFR-TKIs. J Thorac Oncol 11:556–565.  https://doi.org/10.1016/j.jtho.2015.12.103 CrossRefPubMedGoogle Scholar
  3. 3.
    Ali A, Goffin JR, Arnold A, Ellis PM (2013) Survival of patients with non-small-cell lung cancer after a diagnosis of brain metastases. Curr Oncol 20:e300–e306.  https://doi.org/10.3747/co.20.1481 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Crawford S (2013) Is it time for a new paradigm for systemic cancer treatment? Lessons from a century of cancer chemotherapy. Front Pharmacol 4:68.  https://doi.org/10.3389/fphar.2013.00068 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Pearce A, Haas M, Viney R, Pearson SA, Haywood P, Brown C, Ward R (2017) Incidence and severity of self-reported chemotherapy side effects in routine care: a prospective cohort study. PLoS ONE 2(10):e0184360.  https://doi.org/10.1371/journal.pone.0184360 CrossRefGoogle Scholar
  6. 6.
    Koff JL, Ramachandiran S, Bernal-Mizrachi L (2015) A time to kill: targeting apoptosis in cancer. Int J Mol Sci 16:2942–2955.  https://doi.org/10.3390/ijms16022942 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516.  https://doi.org/10.1080/01926230701320337 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Chipuk JE, Fisher JC, Dillon CP, Kriwacki RW, Kuwana T, Green DR (2008) Mechanism of apoptosis induction by inhibition of the anti-apoptotic BCL-2 proteins. Proc Natl Acad Sci U S A 105:20327–20332.  https://doi.org/10.1073/pnas.0808036105 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Plati J, Bucur O, Khosravi-Far R (2011) Apoptotic cell signaling in cancer progression and therapy. Integr Biol (Camb) 3:279–296.  https://doi.org/10.1039/c0ib00144a CrossRefGoogle Scholar
  10. 10.
    Schmidt LH, Görlich D, Spieker T, Rohde C, Schuler M, Mohr M, Humberg J, Sauer T, Thoenissen NH, Huge A, Voss R, Marra A, Faldum A, Müller-Tidow C, Berdel WE, Wiewrodt R (2014) Prognostic impact of Bcl-2 depends on tumor histology and expression of MALAT-1 lncRNA in non-small-cell lung cancer. J Thorac Oncol 9:1294–1304.  https://doi.org/10.1097/jto.0000000000000243 CrossRefPubMedGoogle Scholar
  11. 11.
    Yang T-M, Barbone D, Fennell DA, Broaddus VC (2009) Bcl-2 family proteins contribute to apoptotic resistance in lung cancer multicellular spheroids. Am J Respir Cell Mol Biol 41:14–23.  https://doi.org/10.1165/rcmb.2008-0320OC CrossRefPubMedGoogle Scholar
  12. 12.
    Zhang H, Guttikonda S, Roberts L, Uziel T, Semizarov D, Elmore SW, Leverson JD, Lam LT (2011) Mcl-1 is critical for survival in a subgroup of non-small-cell lung cancer cell lines. Oncogene 30:1963–1968.  https://doi.org/10.1038/onc.2010.559 Epub 2010 Dec 6 CrossRefPubMedGoogle Scholar
  13. 13.
    Chandrika BB, Maney SK, Lekshmi SU, Joseph J, Seervi M, Praveen KS, Santhoshkumar TR (2010) Bax deficiency mediated drug resistance can be reversed by endoplasmic reticulum stress induced death signaling. Biochem Pharmacol 79(11):1589–1599.  https://doi.org/10.1016/j.bcp.2010.01.032 CrossRefPubMedGoogle Scholar
  14. 14.
    Bosanquet AG, Sturm I, Wieder T, Essmann F, Bosanquet MI, Head DJ, Dörken B, Daniel PT (2002) Bax expression correlates with cellular drug sensitivity to doxorubicin, cyclophosphamide and chlorambucil but not fludarabine, cladribine or corticosteroids in B cell chronic lymphocytic leukemia. Leukemia 16(6):1035–1044.  https://doi.org/10.1038/sj.leu.2402539 CrossRefPubMedGoogle Scholar
  15. 15.
    Zhang L, Yu J, Park BH, Kinzler KW, Vogelstein B (2000) Role of BAX in the apoptotic response to anticancer agents. Science 290(5493):989–992CrossRefGoogle Scholar
  16. 16.
    Yu J, Zhang L (2008) PUMA, a potent killer with or without p53. Oncogene 1:S71–S83.  https://doi.org/10.1038/onc.2009.45 CrossRefGoogle Scholar
  17. 17.
    Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288:1053–1058CrossRefGoogle Scholar
  18. 18.
    Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, Green DR (2004) Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303:1010–1014CrossRefGoogle Scholar
  19. 19.
    Hemann M, Lowe S (2006) The p53-Bcl-2 connection. Cell Death Differ 13:1256–1259.  https://doi.org/10.1038/sj.cdd.4401962 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Rueda-Rincon N, Bloch K, Derua R, Vyas R, Harms A, Hankemeier T, Khan NA, Dehairs J, Bagadi M, Binda MM, Waelkens E, Marine JC, Swinnen JV (2015) p53 attenuates AKT signaling by modulating membrane phospholipid composition. Oncotarget 6:21240–21254.  https://doi.org/10.18632/oncotarget.4067 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Drosten M, Sum EY, Lechuga CG, Simón-Carrasco L, Jacob HK, García-Medina R, Huang S, Beijersbergen RL, Bernards R, Barbacid M (2014) Loss of p53 induces cell proliferation via Ras-independent activation of the Raf/Mek/Erk signaling pathway. Proc Natl Acad Sci USA 111:15155–15160.  https://doi.org/10.1073/pnas.1417549111 CrossRefPubMedGoogle Scholar
  22. 22.
    Parrales A, Iwakuma T (2015) Targeting oncogenic mutant p53 for cancer therapy. Front Oncol 5:288.  https://doi.org/10.3389/fonc.2015.00288 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Vazquez A, Bond EE, Levine AJ, Bond GL (2008) The genetics of the p53 pathway, apoptosis and cancer therapy. Nat Rev Drug 7:979–987.  https://doi.org/10.1038/nrd2656 CrossRefGoogle Scholar
  24. 24.
    Nobili S, Lippi D, Witort E, Donnini M, Bausi L, Mini E, Capaccioli S (2009) Natural compounds for cancer treatment and prevention. Pharmacol Res 59:365–378.  https://doi.org/10.1016/j.phrs.2009.01.017 CrossRefPubMedGoogle Scholar
  25. 25.
    Chaotham C, Chanvorachote P (2015) A bibenzyl from Dendrobium ellipsophyllum inhibits migration in lung cancer cells. J Nat Med 69:565–574.  https://doi.org/10.1007/s11418-015-0925-5 CrossRefPubMedGoogle Scholar
  26. 26.
    Chaotham C, Pongrakhananon V, Sritularak B, Chanvorachote P (2014) A Bibenzyl from Dendrobium ellipsophyllum inhibits epithelial-to-mesenchymal transition and sensitizes lung cancer cells to anoikis. Anticancer Res 34:1931–1938PubMedGoogle Scholar
  27. 27.
    Tanagornmeatar K, Chaotham C, Sritularak B, Likhitwitayawuid K, Chanvorachote P (2014) Cytotoxic and anti-metastatic activities of phenolic compounds from Dendrobium ellipsophyllum. Anticancer Res 34:6573–6579PubMedGoogle Scholar
  28. 28.
    Boiarskikh UA, Kondrakhin IuV, Evshin IS, Sharipov RN, Komel’kov AV, Musatkina EA, Chevkina EM, Sukoian MA, Kolpakov FA, Kashkin KN, Filipenko ML (2011) Prediction of a non-small cell lung cancer sensitivity to cisplatin and paclitaxel based on the marker genes expression. Mol Biol (Mosk) 45:652–661Google Scholar
  29. 29.
    van Engeland M, Nieland LJ, Ramaekers FC, Schutte B, Reutelingsperger CP (1998) Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry 31:1–9CrossRefGoogle Scholar
  30. 30.
    Rahman MA, Yang H, Lim SS, Huh SO (2013) Apoptotic effects of Melandryum firmum root extracts in human SH-SY5Y neuroblastoma cells. Exp Neurobiol 22:208–213.  https://doi.org/10.5607/en.2013.22.3.208 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Wang Y, Deng L, Zhong H, Wang Y, Jiang X, Chen J (2011) Natural plant extract tubeimoside I promotes apoptosis-mediated cell death in cultured human hepatoma (HepG2) cells. Biol Pharm Bull 34:831–838CrossRefGoogle Scholar
  32. 32.
    Hsieh YC, Rao YK, Wu CC, Huang CY, Geethangili M, Hsu SL, Tzeng YM (2010) Methyl antcinate A from Antrodia camphorata induces apoptosis in human liver cancer cells through oxidant-mediated cofilin- and Bax-triggered mitochondrial pathway. Chem Res Toxicol 23:1256–1267.  https://doi.org/10.1021/tx100116a CrossRefPubMedGoogle Scholar
  33. 33.
    Zhang Z, Teruya K, Eto H, Shirahata S (2011) Fucoidan extract induces apoptosis in MCF-7 cells via a mechanism involving the ROS-dependent JNK activation and mitochondria-mediated pathways. PLoS ONE 6:e27441.  https://doi.org/10.1371/journal.pone.0027441 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Loayza-Puch F, Drost J, Rooijers K, Lopes R, Elkon R, Agami R (2013) p53 induces transcriptional and translational programs to suppress cell proliferation and growth. Genome Biol 14:R32.  https://doi.org/10.1186/gb-2013-14-4-r32 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Giancotti FG (2014) Deregulation of cell signaling in cancer. FEBS Lett 588:2558–2570.  https://doi.org/10.1016/j.febslet.2014.02.005 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, Sarkar S (2014) Drug resistance in cancer: an overview. Cancers 6:1769–1792.  https://doi.org/10.3390/cancers6031769 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Wangari-Talbot J, Hopper-Borge E (2013) Drug resistance mechanisms in non-small cell lung carcinoma. J Can Res Updates 2:265–282.  https://doi.org/10.6000/1929-2279.2013.02.04.5 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Tsvetkova E, Goss GD (2012) Drug resistance and its significance for treatment decisions in non-small-cell lung cancer. Curr Oncol 19:S45–S51.  https://doi.org/10.3747/co.19.1113 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Coate LE, John T, Tsao MS, Shepherd FA (2009) Molecular predictive and prognostic markers in non-small-cell lung cancer. Lancet Oncol 10:1001–1010.  https://doi.org/10.1016/s1470-2045(09)70155-x CrossRefPubMedGoogle Scholar
  40. 40.
    Tsao MS, Aviel-Ronen S, Ding K, Lau D, Liu N, Sakurada A, Whitehead M, Zhu CQ, Livingston R, Johnson DH, Rigas J, Seymour L, Winton T, Shepherd FA (2007) Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non-small-cell lung cancer. J Clin Oncol 25(33):5240–5247.  https://doi.org/10.1200/JCO.2007.12.6953 CrossRefPubMedGoogle Scholar
  41. 41.
    Steels E, Paesmans M, Berghmans T, Branle F, Lemaitre F, Mascaux C, Meert AP, Vallot F, Lafitte JJ, Sculier JP (2001) Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. Eur Respir J 18(4):705–719CrossRefGoogle Scholar
  42. 42.
    Chakraborty S, Mazumdar M, Mukherjee S, Bhattacharjee P, Adhikary A, Manna A, Chakraborty S, Khan P, Sen A, Das T (2014) Restoration of p53/miR-34a regulatory axis decreases survival advantage and ensures Bax-dependent apoptosis of non-small cell lung carcinoma cells. FEBS Lett 588:549–559.  https://doi.org/10.1016/j.febslet.2013.11.040 CrossRefPubMedGoogle Scholar
  43. 43.
    Wong FC, Woo CC, Hsu A, Tan BK (2013) The anti-cancer activities of Vernonia amygdalina extract in human breast cancer cell lines are mediated through caspase-dependent and p53-independent pathways. PLoS ONE 8:e78021.  https://doi.org/10.1371/journal.pone.0078021 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Lee DH, Kim C, Zhang L, Lee YJ (2008) Role of p53, PUMA, and Bax in wogonin-induced apoptosis in human cancer cells. Biochem Pharmacol 75:2020–2033.  https://doi.org/10.1016/j.bcp.2008.02.023 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Lam M, Carmichael AR, Griffiths HR (2012) An aqueous extract of Fagonia cretica induces DNA damage, cell cycle arrest and apoptosis in breast cancer cells via FOXO3a and p53 expression. PLoS ONE 7(6):e40152.  https://doi.org/10.1371/journal.pone.0040152 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Lane DP, Cheok CF, Lain S (2010) p53-based cancer therapy. Cold Spring Harb Perspect Biol 2:a001222.  https://doi.org/10.1101/cshperspect.a001222 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Fresno Vara JA, Casado E, de Castro J, Cejas P, Belda-Iniesta C, González-Barón M (2004) PI3 K/Akt signalling pathway and cancer. Cancer Treat Rev 30:193–204CrossRefGoogle Scholar
  48. 48.
    Cheng H, Shcherba M, Pendurti G, Liang Y, Piperdi B, Perez-Soler R (2014) Targeting the PI3 K/AKT/mTOR pathway: potential for lung cancer treatment. Lung Cancer Manag 3:67–75.  https://doi.org/10.2217/lmt.13.72 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Sarris EG, Saif MW, Syrigos KN (2012) The biological role of pi3 k pathway in lung cancer. Pharmaceuticals (Basel) 5:1236–1264.  https://doi.org/10.3390/ph5111236 CrossRefGoogle Scholar
  50. 50.
    Nurwidya F, Takahashi F, Murakami A, Takahashi K (2012) Epithelial mesenchymal transition in drug resistance and metastasis of lung cancer. Cancer Res Treat 44:151–156.  https://doi.org/10.4143/crt.2012.44.3.151 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Thomson S, Buck E, Petti F, Griffin G, Brown E, Ramnarine N, Iwata KK, Gibson N, Haley JD (2005) Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res 65:9455–9462.  https://doi.org/10.1158/0008-5472.CAN-05-1058 CrossRefPubMedGoogle Scholar
  52. 52.
    Beerheide W, Tan YJ, Teng E, Ting AE, Jedpiyawongse A, Srivatanakul P (2000) Downregulation of proapoptotic proteins Bax and Bcl-X(S) in p53 overexpressing hepatocellular carcinomas. Biochem Biophys Res Commun 273:54–61.  https://doi.org/10.1006/bbrc.2000.2891 CrossRefPubMedGoogle Scholar
  53. 53.
    Shibue T, Suzuki S, Okamoto H, Yoshida H, Ohba Y, Takaoka A, Taniguchi T (2006) Differential contribution of Puma and Noxa in dual regulation of p53-mediated apoptotic pathways. EMBO J 25:4952–4962.  https://doi.org/10.1038/sj.emboj.7601359 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Zhang M, Zheng J, Nussinov R, Ma B (2017) Release of cytochrome C from Bax pores at the mitochondrial membrane. Sci Rep 7:2635.  https://doi.org/10.1038/s41598-017-02825-7 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Martin B, Paesmans M, Berghmans T, Branle F, Ghisdal L, Mascaux C, Meert AP, Steels E, Vallot F, Verdebout JM, Lafitte JJ, Sculier JP (2003) Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer 89:55–64.  https://doi.org/10.1038/sj.bjc.6601095 CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Wesarg E, Hoffarth S, Wiewrodt R, Kröll M, Biesterfeld S, Huber C, Schuler M (2007) Targeting BCL-2 family proteins to overcome drug resistance in non-small cell lung cancer. Int J Cancer 121:2387–2394.  https://doi.org/10.1002/ijc.22977 CrossRefPubMedGoogle Scholar
  57. 57.
    Luo L, Zhang T, Liu H, Lv T, Yuan D, Yao Y, Lv Y, Song Y (2012) MiR-101 and Mcl-1 in non-small-cell lung cancer: expression profile and clinical significance. Med Oncol 29:1681–1686.  https://doi.org/10.1007/s12032-011-0085-8 CrossRefPubMedGoogle Scholar
  58. 58.
    Mohammad RM, Muqbil I, Lowe L, Yedjou C, Hsu HY, Lin LT, Siegelin MD, Fimognari C, Kumar NB, Dou QP, Yang H, Samadi AK, Russo GL, Spagnuolo C, Ray SK, Chakrabarti M, Morre JD, Coley HM, Honoki K, Fujii H, Georgakilas AG, Amedei A, Niccolai E, Amin A, Ashraf SS, Helferich WG, Yang X, Boosani CS, Guha G, Bhakta D, Ciriolo MR, Aquilano K, Chen S, Mohammed SI, Keith WN, Bilsland A, Halicka D, Nowsheen S, Azmi AS (2015) Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol 35(Suppl):S78–S103.  https://doi.org/10.1016/j.semcancer.2015.03.001 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Lemjabbar-Alaoui H, Hassan OU, Yang YW, Buchanan P (2015) Lung cancer: Biology and treatment options. Biochim Biophys Acta 1856:189–210.  https://doi.org/10.1016/j.bbcan.2015.08.002 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, Scagliotti G, Rosell R, Oliff I, Reeves JA, Wolf MK, Krebs AD, Averbuch SD, Ochs JS, Grous J, Fandi A, Johnson DH (2004) Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial–INTACT 2. J Clin Oncol 22:785–794.  https://doi.org/10.1200/JCO.2004.07.215 CrossRefPubMedGoogle Scholar
  61. 61.
    Koizumi T, Fukushima T, Gomi D, Kobayashi T, Sekiguchi N, Sakamoto A, Sasaki S, Mamiya K (2016) Alectinib-Induced alopecia in a patient with anaplastic lymphoma kinase-positive non-small cell lung cancer. Case Rep Oncol 9:212–215.  https://doi.org/10.1159/000445288 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Chie WC, Yang CH, Hsu C, Yang PC (2004) Quality of life of lung cancer patients: validation of the Taiwan Chinese version of the EORTC QLQ-C30 and QLQ-LC13. Qual Life Res 13:257–262.  https://doi.org/10.1023/B:QURE.0000015295.74812.06 CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Anirut Hlosrichok
    • 1
  • Somruethai Sumkhemthong
    • 1
  • Boonchoo Sritularak
    • 2
  • Pithi Chanvorachote
    • 3
    • 4
  • Chatchai Chaotham
    • 1
    • 4
    Email author
  1. 1.Department of Biochemistry and Microbiology, Faculty of Pharmaceutical SciencesChulalongkorn UniversityBangkokThailand
  2. 2.Departments of Pharmacognosy and Pharmaceutical BotanyChulalongkorn UniversityBangkokThailand
  3. 3.Department of Pharmacology and Physiology, Faculty of Pharmaceutical SciencesChulalongkorn UniversityBangkokThailand
  4. 4.Cell-based Drug and Health Products Development Research Unit, Faculty of Pharmaceutical SciencesChulalongkorn UniversityBangkokThailand

Personalised recommendations