J Appl Biomed 21:23-35, 2023 | DOI: 10.32725/jab.2022.019

As a novel anticancer candidate, ether extract of Dendrobium nobile overstimulates cellular protein biosynthesis to induce cell stress and autophagy

Ruoxi Zhao1, 3, Shigang Zheng1, 3, Ying Li1, 2, Xueqin Zhang1, 2, Dan Rao1, 2, Ze Chun1, 3, Yadong Hu1, 3, *
1 Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China
2 University of Chinese Academy of Sciences, Beijing, China
3 Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing, China

Increasing data has confirmed the potential anticancer properties of Dendrobium, a traditional Chinese herb. However, most anticancer compositions from the plant of Dendrobium were usually extracted by high polar solvent, while weak polar compositions with excellent anticancer activity remained largely unexplored. In this study, the differences between ether extract and ethanol extract of Dendrobium nobile Lindl. on chemical components and anticancer activities were investigated, as well as the anticancer mechanisms among different extracts. The results demonstrated that the ether extract exhibited a stronger anticancer effect than ethanol extract, and its anticancer effect was mainly due to weak polar compounds rather than polysaccharides and alkaloids. Quantitative proteomics suggested that the ether extract significantly stimulated the over-expression of immature proteins, the endoplasmic reticulum stress and unfolded protein response were subsequently induced, the intracellular reactive oxygen species level was seriously elevated, and oxidative stress occurred in the meanwhile. Eventually, autophagy and apoptosis were activated to cause cell death. Our findings demonstrate that the ether extract of D. nobile is a potential candidate for anticancer drug development, and that future research on anticancer drugs derived from medicinal plants should also concentrate on weak polar compounds.

Keywords: Anticancer; Autophagy; Cell stress; Dendrobium nobile; Ether extract
Grants and funding:

This work was supported by Sichuan Science and Technology Program (2018SZ0096, 2020YFN0001, 2021YFYZ0012, 2021YFH0080), and the National Natural Science Foundation of China (No. 32100305).

Conflicts of interest:

The authors have no conflict of interests to declare.

Received: January 27, 2022; Revised: November 30, 2022; Accepted: December 16, 2022; Prepublished online: January 16, 2022; Published: April 1, 2023  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Zhao R, Zheng S, Li Y, Zhang X, Rao D, Chun Z, Hu Y. As a novel anticancer candidate, ether extract of Dendrobium nobile overstimulates cellular protein biosynthesis to induce cell stress and autophagy. J Appl Biomed. 2023;21(1):23-35. doi: 10.32725/jab.2022.019. PubMed PMID: 36708715.
Download citation

Attachments

Download fileJAB_1826_Suppl_materials.pdf

File size: 123.67 kB

References

  1. Al-Shenawy Ha (2016). Expression of Beclin-1, an autophagy-related marker, in chronic hepatitis and hepatocellular carcinoma and its relation with apoptotic markers. APMIS 124(3): 229-237. DOI: 10.1111/apm.12498. Go to original source... Go to PubMed...
  2. Aouidi F, Dupuy N, Artaud J, Roussos S, Msallem M, Perraud-Gaime I, et al. (2012). Discrimination of five Tunisian cultivars by Mid InfraRed spectroscopy combined with chemometric analyses of olive Olea europaea leaves. Food Chemistry 131: 360-366. DOI: 10.1016/j.foodchem.2011.08.041. Go to original source...
  3. Charoenrungruang S, Chanvorachote P, Sritularak B, Pongrakhananon V (2014). Gigantol, a bibenzyl from Dendrobium draconis, inhibits the migratory behavior of non-small cell lung cancer cells. J Nat Prod 77(6): 1359-1366. DOI: 10.1021/np500015v. Go to original source... Go to PubMed...
  4. Chen J-T, Yuan Y, Yu M, Zhang B, Liu X, Zhang J (2019). Comparative nutritional characteristics of the three major Chinese Dendrobium species with different growth years. PloS One 14(9): e0222666. DOI: 10.1371/journal.pone.0222666. Go to original source... Go to PubMed...
  5. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, et al. (2008). The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452(7184): 230-233. DOI: 10.1038/nature06734. Go to original source... Go to PubMed...
  6. Grek CL, Tew KD (2010). Redox metabolism and malignancy. Curr Opin Pharmacol 10(4): 362-368. DOI: 10.1016/j.coph.2010.05.003. Go to original source... Go to PubMed...
  7. Guo Z, Zhou Y, Yang J, Shao X (2019). Dendrobium candidum extract inhibits proliferation and induces apoptosis of liver cancer cells by inactivating Wnt/beta-catenin signaling pathway. Biomed Pharmacother 110: 371-379. DOI: 10.1016/j.biopha.2018.11.149. Go to original source... Go to PubMed...
  8. Hu Y, Wang H, Wang Q, Deng H (2014). Overexpression of CD38 decreases cellular NAD levels and alters the expression of proteins involved in energy metabolism and antioxidant defense. J Proteome Res 13(2): 786-795. DOI: 10.1021/pr4010597. Go to original source... Go to PubMed...
  9. Lam Y, Ng TB, Yao RM, Shi J, Xu K, Sze SC, Zhang KY (2015). Evaluation of chemical constituents and important mechanism of pharmacological biology in Dendrobium plants. Evid Based Complement Alternat Med 2015: 841752. DOI: 10.1155/2015/841752. Go to original source... Go to PubMed...
  10. Lee YH, Park JD, Baek NI, Kim SI, Ahn BZ (1995). In vitro and in vivo antitumoral phenanthrenes from the aerial parts of Dendrobium nobile. Planta Med 61(2): 178-180. DOI: 10.1055/s-2006-958043. Go to original source... Go to PubMed...
  11. Li Y, Liu J, Zhang X, T H, Chun Z, Hu H (2018). Extraction of components with different polarities from Dendrobium and their inhibitory action on lung cancer cells. Chin J Appl Environ Biol 24: 13-19. DOI: 10.19675/j.cnki.1006-687x.2016.08033. Go to original source...
  12. Liu N, Yang HL, Wang P, Lu YC, Yang YJ, Wang L, Lee SC (2016a). Functional proteomic analysis revels that the ethanol extract of Annona muricata L. induces liver cancer cell apoptosis through endoplasmic reticulum stress pathway. J Ethnopharmacol 189: 210-217. DOI: 10.1016/j.jep.2016.05.045. Go to original source... Go to PubMed...
  13. Liu Z, Hu Y, Liang H, Sun Z, Feng S, Deng H (2016b). Silencing PRDX3 Inhibits Growth and Promotes Invasion and Extracellular Matrix Degradation in Hepatocellular Carcinoma Cells. J Proteome Res 15(5): 1506-1514. DOI: 10.1021/acs.jproteome.5b01125. Go to original source... Go to PubMed...
  14. Lu TL, Han CK, Chang YS, Lu TJ, Huang HC, Bao BY, et al. (2014). Denbinobin, a phenanthrene from Dendrobium nobile, impairsprostate cancer migration by inhibiting Rac1 activity. Am J Chin Med 42(6): 1539-1554. DOI: 10.1142/S0192415X14500967. Go to original source... Go to PubMed...
  15. Luo C, He T, Chun Z (2013). Discrimination and chemical phylogenetic study of seven species of Dendrobium using infrared spectroscopy combined with cluster analysis. J Mol Struct 1037: 40-48. DOI: 10.1016/j.molstruc.2012.10.048. Go to original source...
  16. Ng TB, Liu J, Wong JH, Ye X, Wing Sze SC, Tong Y, Zhang KY (2012). Review of research on Dendrobium, a prized folk medicine. Appl Microbiol Biotechnol 93(5): 1795-1803. DOI: 10.1007/s00253-011-3829-7. Go to original source... Go to PubMed...
  17. Ochoa CD, Wu RF, Terada LS (2018). ROS signaling and ER stress in cardiovascular disease. Mol Aspects Med 63: 18-29. DOI: 10.1016/j.mam.2018.03.002. Go to original source... Go to PubMed...
  18. Parekh HS, Liu G, Wei MQ (2009). A new dawn for the use of traditional Chinese medicine in cancer therapy. Mol Cancer 8: 21. DOI: 10.1186/1476-4598-8-21. Go to original source... Go to PubMed...
  19. Prasad R, Koch B (2014). Antitumor activity of ethanolic extract of Dendrobium formosum in T-cell lymphoma: an in vitro and in vivo study. Biomed Res Int 2014: 753451. DOI: 10.1155/2014/753451. Go to original source... Go to PubMed...
  20. Prasad R, Rana NK, Koch B (2017). Dendrobium chrysanthum ethanolic extract induces apoptosis via p53 up-regulation in HeLa cells and inhibits tumor progression in mice. J Complement Integr Med 14(2): 20160070. DOI: 10.1515/jcim-2016-0070. Go to original source... Go to PubMed...
  21. Ramirez MP, Rivera M, Quiroga-Roger D, Bustamante A, Vega M, Baez M, et al. (2017). Single molecule force spectroscopy reveals the effect of BiP chaperone on protein folding. Protein Sci 26(7): 1404-1412. DOI: 10.1002/pro.3137. Go to original source... Go to PubMed...
  22. Roth G, Vanz AL, Lünsdorf H, Nimtz M, Rinas U (2018). Fate of the UPR marker protein Kar2/Bip and autophagic processes in fed-batch cultures of secretory insulin precursor producing Pichia pastoris. Microb Cell Fact 17(1): 123. DOI: 10.1186/s12934-018-0970-3. Go to original source... Go to PubMed...
  23. Sánchez-Martín P, Komatsu M (2018). p62/SQSTM1 - steering the cell through health and disease. J Cell Sci 131(21): jcs222836. DOI: 10.1242/jcs.222836. Go to original source... Go to PubMed...
  24. Sellier C, Campanari ML, Julie Corbier C, Gaucherot A, Kolb-Cheynel I, Oulad-Abdelghani M, et al. (2016). Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death. EMBO J 35(12): 1276-1297. DOI: 10.15252/embj.201593350. Go to original source... Go to PubMed...
  25. Simanshu DK, Nissley DV, McCormick F (2017). RAS Proteins and Their Regulators in Human Disease. Cell 170(1): 17-33. DOI: 10.1016/j.cell.2017.06.009. Go to original source... Go to PubMed...
  26. Smith PJ, Clavarino A, Long J, Steadman KJ (2014). Why do some cancer patients receiving chemotherapy choose to take complementary and alternative medicines and what are the risks? Asia Pac J Clin Oncol 10(1): 1-10. DOI: 10.1111/ajco.12115. Go to original source... Go to PubMed...
  27. Song JI, Kang YJ, Yong HY, Kim YC, Moon A (2012). Denbinobin, a phenanthrene from Dendrobium nobile, inhibits invasion and induces apoptosis in SNU-484 human gastric cancer cells. Oncol Rep 27(3): 813-818. DOI: 10.3892/or.2011.1551. Go to original source... Go to PubMed...
  28. Song TH, Chen XX, Lee CK, Sze SC, Feng YB, Yang ZJ, et al. (2019). Dendrobine targeting JNK stress signaling to sensitize chemotoxicity of cisplatin against non-small cell lung cancer cells in vitro and in vivo. Phytomedicine 53: 18-27. DOI: 10.1016/j.phymed.2018.06.018. Go to original source... Go to PubMed...
  29. Wang H-F, Wang Z-Q, Ding Y, Piao M-H, Feng C-S, Chi G-F, et al. (2018). Endoplasmic reticulum stress regulates oxygen-glucose deprivation-induced parthanatos in human SH-SY5Y cells via improvement of intracellular ROS. CNS Neurosci Ther 24(1): 29-38. DOI: 10.1111/cns.12771. Go to original source... Go to PubMed...
  30. Wang J-H, Luo J-P, Zha X-Q, Feng B-J (2010). Comparison of antitumor activities of different polysaccharide fractions from the stems of Dendrobium nobile Lindl. Carbohydr Polym 79: 114-118. DOI: 10.1016/j.carbpol.2009.07.032. Go to original source...
  31. Wang P, Yang HL, Yang YJ, Wang L, Lee SC (2015). Overcome Cancer Cell Drug Resistance Using Natural Products. Evid Based Complement Alternat Med 2015: 767136. DOI: 10.1155/2015/767136. Go to original source... Go to PubMed...
  32. Wang Q, Sun P, Li G, Zhu K, Wang C, Zhao X (2014). Inhibitory effects of Dendrobium candidum Wall ex Lindl. on azoxymethane- and dextran sulfate sodium-induced colon carcinogenesisin C57BL/6 mice. Oncol Lett 7(2): 493-498. DOI: 10.3892/ol.2013.1728. Go to original source... Go to PubMed...
  33. Xin X, Wen T, Gong LB, Deng MM, Hou KZ, Xu L, et al. (2020). Inhibition of FEN1 Increases Arsenic Trioxide-Induced ROS Accumulation and Cell Death: Novel Therapeutic Potential for Triple Negative Breast Cancer. Front Oncol 10: 425. DOI: 10.3389/fonc.2020.00425. Go to original source... Go to PubMed...
  34. Xing S, Zhang X, Ke H, Lin J, Huang Y, Wei G (2018). Physicochemical properties of polysaccharides from Dendrobium officinale by fractional precipitation and their preliminary antioxidant and anti-HepG2 cells activities in vitro. Chem Cent J 12(1): 100. DOI: 10.1186/s13065-018-0468-4. Go to original source... Go to PubMed...
  35. Xu G, Wang X, Yu H, Wang C, Liu Y, Zhao R, Zhang G (2019). Beclin 1, LC3, and p62 expression in paraquat-induced pulmonary fibrosis. Hum Exp Toxicol 38(7): 794-802. DOI: 10.1177/0960327119842633. Go to original source... Go to PubMed...
  36. Yang H, Lee PJ, Jeong EJ, Kim HP, Kim YC (2012). Selective apoptosis in hepatic stellate cells mediates the antifibrotic effect of phenanthrenes from Dendrobium nobile. Phytother Res 26(7): 974-980. DOI: 10.1002/ptr.3632. Go to original source... Go to PubMed...
  37. Yip KM, Xu J, Tong WS, Zhou SS, Yi T, Zhao ZZ, Chen HB (2016). Ultrasound-assisted extraction may not be a better alternative approach than conventional boiling for extracting polysaccharides from herbal medicines. Molecules 21(11): 1569. DOI: 10.3390/molecules21111569. Go to original source... Go to PubMed...
  38. Zhang YY, Zhang QQ, Xin W, Liu N, Zhang H (2019). Nudol, a phenanthrene derivative from Dendrobium nobile, induces cellcycle arrest and apoptosis and inhibits migration in osteosarcoma cells. Drug Des Devel Ther 13: 2591-2601. DOI: 10.2147/DDDT.S180610. Go to original source... Go to PubMed...
  39. Zhao X, Sun P, Qian Y, Suo H (2014). D. candidum has in vitro anticancer effects in HCT-116 cancer cells and exerts in vivo anti-metastatic effects in mice. Nutr Res Pract 8(5): 487-493. DOI: 10.4162/nrp.2014.8.5.487. Go to original source... Go to PubMed...
  40. Zhao Y, Liu Y, Lan XM, Xu GL, Sun YZ, Li F, Liu HN (2016). Effect of Dendrobium officinale extraction on gastric carcinogenesis in rats. Evid Based Complement Alternat Med 2016: 1213090. DOI: 10.1155/2016/1213090. Go to original source... Go to PubMed...
  41. Zheng Q, Qiu D, Liu X, Zhang L, Cai S, Zhang X (2015). Antiproliferative effect of Dendrobium catenatum Lindley polypeptides against human liver, gastric and breast cancer cell lines. Food Funct 6(5): 1489-1495. DOI: 10.1039/c5fo00060b. Go to original source... Go to PubMed...
  42. Zheng S, Han F, Shi Y, Wen L, Han D (2017). Single-prolonged-stress-induced changes in autophagy-related proteins beclin-1, LC3, and p62 in the medial prefrontal cortex of rats with post-traumatic stress disorder. J Mol Neurosci 62(1): 43-54. DOI: 10.1007/s12031-017-0909-x. Go to original source... Go to PubMed...
  43. Zheng S, Hu Y, Zhao R, Zhao T, Li H, Rao D, Chun Z (2020). Quantitative assessment of secondary metabolites and cancer cell inhibiting activity by high performance liquid chromatography fingerprinting in Dendrobium nobile. J Chromatogr B Analyt Technol Biomed Life Sci 1140: 122017. DOI: 10.1016/j.jchromb.2020.122017. Go to original source... Go to PubMed...

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0), which permits non-comercial use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.