Vernodalin Triggers ROS-Mediated Apoptosis in TPC-1 Human Papillary Thyroid Cancer Cells via Suppression of the MAPKs Signaling Pathway


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Abstract

Background:Thyroid Cancer (TC) is an endocrine organ malignancy that has become more common in recent decades. Vernodalin (VN), a cytotoxic sesquiterpene, has been reported to exhibit anticancer properties against human breast and liver cancer cells. However, no study has explored the efficacy of VN with respect to its antiproliferative and apoptotic action on human Papillary Thyroid Cancer cells (PTC).

Objective:The study intended to examine the antitumor and antiproliferative effects of VN and the apoptosis mechanisms underlying its action on TPC-1 human PTC cells.

Methods:In this study, we examined the VN cell viability by MTT assay; performed ROS measurement by DCFH staining method, MMP identification by Rh-123 staining method, and apoptotic morphological assay by employing AO/EB and DAPI stain method, and further, p38 MAPK/ERK/JNK cell proliferation markers were determined by western blotting technique.

Results:The findings showed that VN could inhibit the growth of PTC cells by increasing intracellular ROS, damaging MMP, and stimulating apoptosis in a concentration-dependent manner. The study demonstrated how VN inhibited TPC-1 cell viability by causing ROS-induced cell death via the MAPK signaling pathway.

Conclusion:VN may serve as an agonist to impact apoptosis in PTC cells. In human PTC, VN could play an effective role in chemotherapy. More studies pertaining to animal tumor models are needed to prove its anti-cancer effectiveness in vivo.

About the authors

Xijia Yang

Department of General Surgery, Xi'an Gaoxin Hospital

Email: info@benthamscience.net

Meng Wei

Dialysis Department of Nephrology Hospital, The First Affiliated Hospital of Xi’an Jiaotong University

Email: info@benthamscience.net

Yuan An

Department of Head and Neck Surgery, Shaanxi Provincial Tumor Hospital, The Affiliated Hospital of Xi'an Jiaotong Univesity

Email: info@benthamscience.net

Qinlong Liang

Department of Head and Neck Surgery, Shaanxi Provincial Tumor Hospital,, The Affiliated Hospital of Xi'an Jiaotong Univesity

Email: info@benthamscience.net

Jing Nan

Department of Head and Neck Surgery, Shaanxi Provincial Tumor Hospital, The Affiliated Hospital of Xi'an Jiaotong Univesity

Email: info@benthamscience.net

Annamalai Vijayalakshmi

, Galileovasan Offshore and Research And Development Pvt. Ltd

Email: info@benthamscience.net

Zizhang Wang

Department of Head and Neck Surgery, Shaanxi Provincial Tumor Hospital, The Affiliated Hospital of Xi'an Jiaotong Univesity

Author for correspondence.
Email: info@benthamscience.net

References

  1. Carling, T.; Udelsman, R. Thyroid Cancer. Annu. Rev. Med., 2014, 65(1), 125-137. doi: 10.1146/annurev-med-061512-105739 PMID: 24274180
  2. Asa, S.L.; Mete, O. Endocrine pathology: Past, present and future. Pathology, 2018, 50(1), 111-118. doi: 10.1016/j.pathol.2017.09.003 PMID: 29132721
  3. Enewold, L.; Zhu, K.; Ron, E.; Marrogi, A.J.; Stojadinovic, A.; Peoples, G.E.; Devesa, S.S. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980-2005. Cancer Epidemiol. Biomarkers Prev., 2009, 18(3), 784-791. doi: 10.1158/1055-9965.EPI-08-0960 PMID: 19240234
  4. Schlumberger, M.; Sherman, S.I. Clinical trials for progressive differentiated thyroid cancer: Patient selection, study design, and recent advances. Thyroid, 2009, 19(12), 1393-1400. doi: 10.1089/thy.2009.1603 PMID: 20001721
  5. Kojic, K.L.; Kojic, S.L.; Wiseman, S.M. Differentiated thyroid cancers: A comprehensive review of novel targeted therapies. Expert Rev. Anticancer Ther., 2012, 12(3), 345-357. doi: 10.1586/era.12.8 PMID: 22369326
  6. Mazzaferri, E.L.; Kloos, R.T. Clinical review 128: Current approaches to primary therapy for papillary and follicular thyroid cancer. J. Clin. Endocrinol. Metab., 2001, 86(4), 1447-1463. doi: 10.1210/jcem.86.4.7407 PMID: 11297567
  7. Shaha, A.R. Implications of prognostic factors and risk groups in the management of differentiated thyroid cancer. Laryngoscope, 2004, 114(3), 393-402. doi: 10.1097/00005537-200403000-00001 PMID: 15091208
  8. Ameziane El Hassani, R.; Buffet, C.; Leboulleux, S.; Dupuy, C.; Dupuy, C. Oxidative stress in thyroid carcinomas: Biological and clinical significance. Endocr. Relat. Cancer, 2019, 26(3), R131-R143. doi: 10.1530/ERC-18-0476 PMID: 30615595
  9. Brieger, K.; Schiavone, S.; Miller, J., Jr; Krause, K.H. Reactive oxygen species: From health to disease. Swiss Med. Wkly., 2012, 142, w13659. doi: 10.4414/smw.2012.13659 PMID: 22903797
  10. Chatterjee, A.; Dutta, C.P. Alkaloids of Piper longum Linn. I. Structure and synthesis of piperlongumine and piperlonguminine. Tetrahedron, 1967, 23(4), 1769-1781. doi: 10.1016/S0040-4020(01)82575-8 PMID: 6047519
  11. Song, X.; Gao, T.; Lei, Q.; Zhang, L.; Yao, Y.; Xiong, J. Piperlongumine induces apoptosis in human melanoma cells via reactive oxygen species mediated mitochondria disruption. Nutr. Cancer, 2018, 70(3), 502-511. doi: 10.1080/01635581.2018.1445769 PMID: 29543494
  12. Aggeli, I.K.S.; Gaitanaki, C.; Beis, I. Involvement of JNKs and p38-MAPK/MSK1 pathways in H2O2-induced upregulation of heme oxygenase-1 mRNA in H9c2 cells. Cell. Signal., 2006, 18(10), 1801-1812. doi: 10.1016/j.cellsig.2006.02.001 PMID: 16531007
  13. Shen, H.M.; Liu, Z. JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species. Free Radic. Biol. Med., 2006, 40(6), 928-939. doi: 10.1016/j.freeradbiomed.2005.10.056 PMID: 16540388
  14. Tripathi, S.K.; Biswal, B.K. Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent. Pharmacol. Res., 2020, 156, 104772. doi: 10.1016/j.phrs.2020.104772 PMID: 32283222
  15. Li, W.; Wen, C.; Bai, H.; Wang, X.; Zhang, X.; Huang, L.; Yang, X.; Iwamoto, A.; Liu, H. JNK signaling pathway is involved in piperlongumine-mediated apoptosis in human colorectal cancer HCT116 cells. Oncol. Lett., 2015, 10(2), 709-715. doi: 10.3892/ol.2015.3371 PMID: 26622558
  16. Morales-Escobar, L.; Braca, A.; Pizza, C.; Tommasi, N.D. New phenolic derivatives from Vernonia mapirensis Gleason. ARKIVOC, 2007, 2007(7), 349-358. doi: 10.3998/ark.5550190.0008.731
  17. Igual, M.O.; Martucci, M.E.P.; Da Costa, F.B.; Gobbo-Neto, L. Sesquiterpene lactones, chlorogenic acids and flavonoids from leaves of Vernonia polyanthes Less (Asteraceae). Biochem. Syst. Ecol., 2013, 51, 94-97. doi: 10.1016/j.bse.2013.08.018
  18. Looi, CY.; Arya, A.; Cheah, FK. Induction of apoptosis in human breast cancer cells via caspase pathway by vernodalin isolated from Centratherum anthelminticum. PLoS One, 2013, 8(2), 56643. doi: 10.1371/journal.pone.0056643
  19. Ananda Sadagopan, S.K.; Mohebali, N.; Looi, C.Y.; Hasanpourghadi, M.; Pandurangan, A.K.; Arya, A.; Karimian, H.; Mustafa, M.R. Forkhead box transcription factor (FOXO3a) mediates the cytotoxic effect of vernodalin in vitro and inhibits the breast tumor growth in vivo. J. Exp. Clin. Cancer Res., 2015, 34(1), 147. doi: 10.1186/s13046-015-0266-y PMID: 26643256
  20. Orlandella, F.M.; Mirabelli, P.; De Stefano, A.E.; Iervolino, P.L.C.; Luciano, N.; D’Angelo, S.; Salvatore, G. Effects of annurca flesh apple polyphenols in human thyroid cancer cell lines. Oxid. Med. Cell. Longev., 2022, 2022, 1-14. doi: 10.1155/2022/6268755 PMID: 35222800
  21. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63. doi: 10.1016/0022-1759(83)90303-4 PMID: 6606682
  22. Velu, P.; Vijayalakshmi, A.; Vinothkumar, V. Retracted: Syringic acid suppresses oral squamous cell carcinoma SCC131 cell proliferation via modulation of mitochondria-mediated apoptosis signaling pathways. J. Biochem. Mol. Toxicol., 2020, 34(12), e22586. doi: 10.1002/jbt.22586 PMID: 32711406
  23. Kasibhatla, S; Amarante-Mendes, GP; Finucane, D . Acridine Orange/ Ethidium Bromide (AO/EB) staining to detect apoptosis. CSH Protoc., 2006, 2006(3), pdb.prot4493.. doi: 10.1101/pdb.prot4493
  24. Yin, F.; Giuliano, A.; Van Herle, A.J. Growth inhibitory effects of flavonoids in human thyroid cancer cell lines. Thyroid, 1999, 9(4), 369-376. doi: 10.1089/thy.1999.9.369 PMID: 10319943
  25. Looi, C.Y.; Moharram, B.; Paydar, M.; Wong, Y.L.; Leong, K.H.; Mohamad, K.; Arya, A.; Wong, W.F.; Mustafa, M.R. Induction of apoptosis in melanoma A375 cells by a chloroform fraction of Centratherum anthelminticum (L.) seeds involves NF-kappaB, p53 and Bcl-2-controlled mitochondrial signaling pathways. BMC Complement. Altern. Med., 2013, 13(1), 166. doi: 10.1186/1472-6882-13-166 PMID: 23837445
  26. Normile, D. Cell proliferation. Common control for cancer, stem cells. Science, 2002, 298(5600), 1869. doi: 10.1126/science.298.5600.1869 PMID: 12471231
  27. Hu, X.; Ma, J.; Vikash, V.; Li, J.; Wu, D.; Liu, Y.; Zhang, J.; Dong, W. Thymoquinone augments cisplatin-induced apoptosis on esophageal carcinoma through mitigating the activation of jak2/stat3 pathway. Dig. Dis. Sci., 2018, 63(1), 126-134. doi: 10.1007/s10620-017-4856-8 PMID: 29197940
  28. Kasim, L.S.; Ferro, V.; Odukoya, O.A.; Ukpo, G.E.; Seidel, V.; Gray, A.I.; Waigh, R. Cytotoxicity of isolated compounds from the extracts of Struchium sparganophora (Linn) Ktze asteraceae. Pak. J. Pharm. Sci., 2011, 24(4), 475-478. PMID: 21959807
  29. Kupchan, S.M.; Hemingway, R.J.; Karim, A.; Werner, D. Tumor inhibitors. XLVII. Vernodalin and vernomygdin, two new cytotoxic sesquiterpene lactones from Vernonia amygdalina del. J. Org. Chem., 1969, 34(12), 3908-3911. doi: 10.1021/jo01264a035 PMID: 5357533
  30. Sznarkowska, A.; Kostecka, A.; Meller, K.; Bielawski, K.P. Inhibition of cancer antioxidant defense by natural compounds. Oncotargeīt 1969, 34(12), 3908-3911. doi: 10.1021/jo01264a035
  31. Engel, R.H.; Evens, A.M. Oxidative stress and apoptosis: A new treatment paradigm in cancer. Front. Biosci., 2006, 11(1), 300-312. doi: 10.2741/1798 PMID: 16146732
  32. Schieber, M.; Chandel, N.S. ROS function in redox signaling and oxidative stress. Curr. Biol., 2014, 24(10), R453-R462. doi: 10.1016/j.cub.2014.03.034 PMID: 24845678
  33. Mühleisen, L.; Alev, M.; Unterweger, H.; Subatzus, D.; Pöttler, M.; Friedrich, R.; Alexiou, C.; Janko, C. Analysis of hypericin-mediated effects and implications for targeted photodynamic therapy. Int. J. Mol. Sci., 2017, 18(7), 1388. doi: 10.3390/ijms18071388 PMID: 28661430
  34. Buytaert, E.; Dewaele, M.; Agostinis, P. Molecular effectors of multiple cell death pathways initiated by photodynamic therapy. Biochim. Biophys. Acta Rev. Cancer, 2007, 1776(1), 86-107. doi: 10.1016/j.bbcan.2007.07.001 PMID: 17693025
  35. Mohebali, N.; Pandurangan, A.K.; Mustafa, M.R.; Anandasadagopan, S.K.; Alagumuthu, T. Vernodalin induces apoptosis through the activation of ROS/JNK pathway in human colon cancer cells. J. Biochem. Mol. Toxicol., 2020, 34(12), e22587. doi: 10.1002/jbt.22587 PMID: 32726518
  36. Gogvadze, V.; Orrenius, S.; Zhivotovsky, B. Mitochondria in cancer cells: What is so special about them? Trends Cell Biol., 2008, 18(4), 165-173. doi: 10.1016/j.tcb.2008.01.006 PMID: 18296052
  37. Chinnaiyan, A.M. The apoptosome: Heart and soul of the cell death machine. Neoplasia, 1999, 1(1), 5-15. doi: 10.1038/sj.neo.7900003 PMID: 10935465
  38. Liou, G.Y.; Storz, P. Reactive oxygen species in cancer. Free Radic. Res., 2010, 44(5), 479-496. doi: 10.3109/10715761003667554 PMID: 20370557
  39. Smolensky, D.; Rhodes, D.; McVey, D.S.; Fawver, Z.; Perumal, R.; Herald, T.; Noronha, L. High-polyphenol sorghum bran extract inhibits cancer cell growth through ros induction, cell cycle arrest, and apoptosis. J. Med. Food, 2018, 21(10), 990-998. doi: 10.1089/jmf.2018.0008 PMID: 29733262
  40. Wu, H.; Fu, X.; Cao, W.; Xiang, W.; Hou, Y.; Ma, J.; Wang, Y.; Fan, C. Induction of apoptosis in human glioma cells by fucoxanthin via triggering of ROS-mediated oxidative damage and regulation of MAPKs and PI3K–AKT pathways. J. Agric. Food Chem., 2019, 67(8), 2212-2219. doi: 10.1021/acs.jafc.8b07126 PMID: 30688446
  41. Drexler, H.G. Review of alterations of the cyclin-dependent kinase inhibitor INK4 family genes p15, p16, p18 and p19 in human leukemia–lymphoma cells. Leukemia, 1998, 12(6), 845-859. doi: 10.1038/sj.leu.2401043 PMID: 9639410

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