DOI QR코드

DOI QR Code

Methanolic Extract from Sea Cucumber, Holothuria scabra, Induces Apoptosis and Suppresses Metastasis of PC3 Prostate Cancer Cells Modulated by MAPK Signaling Pathway

  • Received : 2021.03.19
  • Accepted : 2021.04.27
  • Published : 2021.06.28

Abstract

Sea cucumber, Holothuria scabra, is a well-known traditional Asian medicine that has been used for suppressing inflammation, promoting wound healing, and improving immunity. Moreover, previous studies demonstrated that the extract from H. scabra contains many bioactive compounds with potent inhibitory effect on tumor cell survival and progression. However, the effect of the methanolic extract from the body wall of H. scabra (BWMT) on human prostate cancer cells has not yet been investigated. In this study, we aimed to investigate the effects and underlying mechanism of BWMT on prostate cancer cell viability and metastasis. BWMT was obtained by maceration with methanol. The effect of BWMT on cell viability was assessed by MTT and colony formation assays. The intracellular ROS accumulation was evaluated using a DCFH-DA fluorescence probe. Hoechst 33342 staining and Annexin V-FITC/PI staining were used to examine the apoptotic-inducing effect of the extract. A transwell migration assay was performed to determine the anti-metastasis effect. BWMT significantly reduced cell viability and triggered cellular apoptosis by accumulating intracellular ROS resulting in the upregulation of JNK and p38 signaling pathways. In addition, BWMT also inhibited the invasion of PC3 cells by downregulating MMP-2/-9 expression via the ERK pathway. Consequently, our study provides BWMT from H. scabra as a putative therapeutic agent that could be applicable against prostate cancer progression.

Keywords

Acknowledgement

This research was supported by the Agricultural Research Development Agency (Public Organization) and the Central Instrument Facility (CIF) Grant, Faculty of Science, Mahidol University, Bangkok, Thailand.

References

  1. Archer M, Dogra N, Kyprianou N. 2020. Inflammation as a driver of prostate cancer metastasis and therapeutic resistance. Cancers 12: 2984. https://doi.org/10.3390/cancers12102984
  2. Khan F, Pandey P, Jha NK, Jafri A, Khan I. 2020. Antiproliferative effect of Moringa oleifera methanolic leaf extract by down-regulation of Notch signaling in DU145 prostate cancer cells. Gene Rep. 19: 100619. https://doi.org/10.1016/j.genrep.2020.100619
  3. Su B, Zhang L, Zhuang W, Zhang W, Chen X. 2021. Knockout of Akt1/2 suppresses the metastasis of human prostate cancer cells CWR22rv1 in vitro and in vivo. J. Cell. Mol. Med. 25: 1546-1553. https://doi.org/10.1111/jcmm.16246
  4. Jaglanian A, Termini D, Tsiani E. 2020. Rosemary (Rosmarinus officinalis L.) extract inhibits prostate cancer cell proliferation and survival by targeting Akt and mTOR. Biomed. Pharmacother. 131: 110717. https://doi.org/10.1016/j.biopha.2020.110717
  5. Wang H, Zhao L, Wu J, Hong J, Wang S. 2020. Propofol induces ROS-mediated intrinsic apoptosis and migration in triple-negative breast cancer cells. Oncol. Lett. 20: 810-816. https://doi.org/10.3892/ol.2020.11608
  6. Wang J-R, Li T-Z, Wang C, Li S-M, Luo Y-H, Piao X-J, et al. 2020. Liquiritin inhibits proliferation and induces apoptosis in HepG2 hepatocellular carcinoma cells via the ROS-mediated MAPK/AKT/NF-κB signaling pathway. Naunyn Schmiedebergs Arch. Pharmacol. 393: 1987-1999. https://doi.org/10.1007/s00210-019-01763-7
  7. Shen CJ, Chang KY, Lin BW, Lin WT, Su CM, Tsai JP, et al. 2020. Oleic acid-induced NOX4 is dependent on ANGPTL4 expression to promote human colorectal cancer metastasis. Theranostics 10: 7083-7099. https://doi.org/10.7150/thno.44744
  8. Zhang D, Chen Y, Xu X, Xiang H, Shi Y, Gao Y, et al. 2020. Autophagy inhibits the mesenchymal stem cell aging induced by D-galactose through ROS/JNK/p38 signalling. Clin. Exp. Pharmacol. Physiol. 47: 466-477. https://doi.org/10.1111/1440-1681.13207
  9. Deng Y, Li Y, Yang F, Zeng A, Yang S, Luo Y, et al. 2017. The extract from Punica granatum (pomegranate) peel induces apoptosis and impairs metastasis in prostate cancer cells. Biomed. Pharmacother. 93: 976-984. https://doi.org/10.1016/j.biopha.2017.07.008
  10. Cui H, Bashar MAE, Rady I, El-Naggar HA, Abd El-Maoula LM, Mehany ABM. 2020. Antiproliferative Activity, Proapoptotic Effect, and Cell Cycle Arrest in Human Cancer Cells of Some Marine Natural Product Extract. Oxid. Med. Cell. Longev. 2020: 7948705.
  11. Pranweerapaiboon K, Apisawetakan S, Nobsathian S, Itharat A, Sobhon P, Chaithirayanon K. 2020. An ethyl-acetate fraction of Holothuria scabra modulates inflammation in vitro through inhibiting the production of nitric oxide and pro-inflammatory cytokines via NF-κB and JNK pathways. Inflammopharmacology 28: 1027-1037. https://doi.org/10.1007/s10787-019-00677-3
  12. Yuan L, Huang X, Zhou K, Zhu X, Huang B, Qiu S, et al. 2019. Sea cucumber extract TBL-12 inhibits the proliferation, migration, and invasion of human prostate cancer cells through the p38 mitogen-activated protein kinase and intrinsic caspase apoptosis pathway. Prostate 79: 826-839. https://doi.org/10.1002/pros.23788
  13. Yurasakpong L, Apisawetakan S, Pranweerapaiboon K, Sobhon P, Chaithirayanon K. 2020. Holothuria scabra Extract induces cell apoptosis and suppresses warburg effect by down-regulating Akt/mTOR/HIF-1 axis in MDA-MB-231 breast cancer cells. Nutr. Cancer. 3: 1-12. https://doi.org/10.1080/01635588109513721
  14. Hoang L, Le Thi V, Tran Thi Hong H, Nguyen Van T, Nguyen Xuan C, Nguyen Hoai N, et al. 2020. Triterpene glycosides from the Vietnamese sea cucumber Holothuria edulis. Nat. Prod. Res. 34: 1061-1067. https://doi.org/10.1080/14786419.2018.1548451
  15. Kim JL, Park SH, Jeong S, Kim BR, Na YJ, Jo MJ, et al. 2019. Sea Cucumber (Stichopus japonicas) F2 enhanced TRAIL-induced apoptosis via XIAP ubiquitination and ER stress in colorectal cancer cells. Nutrients 11: 1061. https://doi.org/10.3390/nu11051061
  16. Arast Y, Seyed Razi N, Nazemi M, Seydi E, Pourahmad J. 2018. Non-polar compounds of Persian Gulf sea cucumber Holothuria parva selectively induce toxicity on skin mitochondria isolated from animal model of melanoma. Cutan. Ocul. Toxicol. 37: 218-227. https://doi.org/10.1080/15569527.2017.1414227
  17. Ding R, Ning X, Ye M, Yin Y. 2021. Antrodia camphorata extract (ACE)-induced apoptosis is associated with BMP4 expression and p53-dependent ROS generation in human colon cancer cells. J. Ethnopharmacol. 268: 113570. https://doi.org/10.1016/j.jep.2020.113570
  18. Liu QR, Liu JM, Chen Y, Xie XQ, Xiong XX, Qiu XY, et al. 2014. Piperlongumine inhibits migration of glioblastoma cells via activation of ROS-dependent p38 and JNK signaling pathways. Oxid. Med. Cell. Longev. 2014: 653732. https://doi.org/10.1155/2014/653732
  19. Attoub S, Arafat K, Gelaude A, Al Sultan MA, Bracke M, Collin P, et al. 2013. Frondoside a suppressive effects on lung cancer survival, tumor growth, angiogenesis, invasion, and metastasis. PLoS One 8: e53087. https://doi.org/10.1371/journal.pone.0053087
  20. Grauso L, Yegdaneh A, Sharifi M, Mangoni A, Zolfaghari B, Lanzotti V. 2019. Molecular networking-based analysis of cytotoxic saponins from sea cucumber Holothuria atra. Mar. Drugs 17: 86. https://doi.org/10.3390/md17020086
  21. Wargasetia TL, Widodo. 2017. Mechanisms of cancer cell killing by sea cucumber-derived compounds. Invest. New Drugs 35: 820-826. https://doi.org/10.1007/s10637-017-0505-5
  22. Sangpairoj K, Chaithirayanon K, Vivithanaporn P, Siangcham T, Jattujan P, Poomtong T, et al. 2016. Extract of the sea cucumber, Holothuria scabra, induces apoptosis in human glioblastoma cell lines. Funct. Foods Health Dis. 6: 452. https://doi.org/10.31989/ffhd.v6i7.264
  23. Seydi E, Motallebi A, Dastbaz M, Dehghan S, Salimi A, Nazemi M, et al. 2015. Selective toxicity of persian gulf sea cucumber (Holothuria parva) and sponge (Haliclona oculata) methanolic extracts on liver mitochondria isolated from an animal model of hepatocellular carcinoma. Hepat. Mon. 15: e33073-e33073. https://doi.org/10.5812/hepatmon.33073
  24. Boonstra J, Post JA. 2004. Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells. Gene 337: 1-13. https://doi.org/10.1016/j.gene.2004.04.032
  25. Cui H, Bashar MAE, Rady I, El-Naggar HA, Abd El-Maoula LM, Mehany ABM. 2020. Antiproliferative activity, proapoptotic effect, and cell cycle arrest in human cancer cells of some marine natural product extract. Oxid. Med. Cell. Longev. 2020: 7948705-7948705.
  26. Rancourt RC, Hayes DD, Chess PR, Keng PC, O'Reilly MA. 2002. Growth arrest in G1 protects against oxygen-induced DNA damage and cell death. J. Cell. Physiol. 193: 26-36. https://doi.org/10.1002/jcp.10146
  27. Thangaraj K, Balasubramanian B, Park S, Natesan K, Liu W, Manju V. 2019. Orientin induces G0/G1 cell cycle arrest and mitochondria mediated intrinsic apoptosis in human colorectal carcinoma HT29 cells. Biomolecules 9: 418. https://doi.org/10.3390/biom9090418
  28. Sun YS, Thakur K, Hu F, Cespedes-Acuna CL, Zhang JG, Wei ZJ. 2020. Icariside II suppresses cervical cancer cell migration through JNK modulated matrix metalloproteinase-2/9 inhibition in vitro and in vivo. Biomed. Pharmacother. 125: 110013. https://doi.org/10.1016/j.biopha.2020.110013
  29. Najafi M, Ahmadi A, Mortezaee K. 2019. Extracellular-signal-regulated kinase/mitogen-activated protein kinase signaling as a target for cancer therapy: an updated review. Cell Biol. Int. 43: 1206-1222. https://doi.org/10.1002/cbin.11187
  30. Park GB, Choi Y, Kim YS, Lee HK, Kim D, Hur DY. 2014. ROS-mediated JNK/p38-MAPK activation regulates Bax translocation in Sorafenib-induced apoptosis of EBV-transformed B cells. Int. J. Oncol. 44: 977-985. https://doi.org/10.3892/ijo.2014.2252
  31. von Thun A, Birtwistle M, Kalna G, Grindlay J, Strachan D, Kolch W, et al. 2012. ERK2 drives tumour cell migration in three-dimensional microenvironments by suppressing expression of Rab17 and liprin-β2. J. Cell Sci. 125: 1465-1477. https://doi.org/10.1242/jcs.092916
  32. Chien ST, Shi MD, Lee YC, Te CC, Shih YW. 2015. Galangin, a novel dietary flavonoid, attenuates metastatic feature via PKC/ERK signaling pathway in TPA-treated liver cancer HepG2 cells. Cancer Cell Int. 15: 15. https://doi.org/10.1186/s12935-015-0168-2
  33. Li S, Cong C, Liu Y, Liu X, Liu H, Zhao L, et al. 2021. Tiao Geng decoction inhibits tributyltin chloride-induced GT1-7 neuronal apoptosis through ASK1/MKK7/JNK signaling pathway. J. Ethnopharmacol. 269: 113669. https://doi.org/10.1016/j.jep.2020.113669
  34. Wang Z, Yu K, Hu Y, Su F, Gao Z, Hu T, et al. 2020. Schisantherin A induces cell apoptosis through ROS/JNK signaling pathway in human gastric cancer cells. Biochem. Pharmacol. 173: 113673. https://doi.org/10.1016/j.bcp.2019.113673
  35. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. 1995. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science (New York, NY.) 270: 1326-1331. https://doi.org/10.1126/science.270.5240.1326