Schisandrin B Inhibits Cell Viability and Malignant Progression of Melanoma Cells via Wnt/β-catenin Signaling Pathway


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Background: Melanoma is of great interest due to its aggressive behavior and less favorable prognosis. The need for the development of novel drugs for the treatment of melanoma is urgent. Considerable evidence indicated that Schisandrin B (Sch B), a bioactive compound extracted from Schisandra chinensis, has numerous anti-tumor properties in multiple malignant tumors. A few studies have reported the effect of Sch B on melanogenesis in the melanoma B16F10 cell line; however, the specific anti-tumor effects and mechanisms need to be further explored.

Objective: This study aimed to investigate the effects of Sch B on the cell viability, migration, invasion, and cell cycleblocking of melanoma cells and explore its potential anti-tumor mechanism in vitro and in vivo.

Methods: Melanoma cells (A375 and B16) were treated with different concentrations of Sch B (0, 20, 40, 60, or 80 µM), with dimethyl sulfoxide (DMSO) as control. The inhibitory effect of Sch B on A375 and B16 melanoma cells was verified by crystal violet assay and CCK8 assay. The flow cytometry was performed to observe cell cycle blocking. The effect of Sch B on the migration and invasion of melanoma cells was detected by wound healing assay and transwell assay, respectively. Western blot analysis was used to determine protein expression levels. The growth of the A375 melanoma xenograft-treated groups and immunohistochemical staining were conducted to assess the anti-tumor effect of Sch B in vivo.

Results: The crystal violet assay and CCK8 assay showed that Sch B significantly inhibited melanoma cell viability in a dose-dependent manner. Meanwhile, the flow cytometry analysis revealed that Sch B induced melanoma cell cycleblocking at the G1/S phase. In addition, the wound healing assay and transwell assay showed that Sch B inhibited the migration and invasion of melanoma cells. Furthermore, by establishing an animal model, we found that Sch B significantly inhibited the growth of melanoma in vivo. The potential mechanism could be that Sch B inhibited the activity of the Wnt/β-catenin signaling pathway.

Conclusion: These findings indicated that Sch B inhibits the cell viability and malignant progression of melanoma cells via the Wnt/β-catenin pathway and induces cell cycle arrest. Our study suggests that Sch B has potential as a bioactive compound for the development of new drugs for melanoma.

Об авторах

Jiayi Chen

Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University,

Email: info@benthamscience.net

Lingzhao Zhang

Department of Dermatology, The Affiliated Children's Hospital of Chongqing Medical University

Email: info@benthamscience.net

Yihuan Pu

Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University

Email: info@benthamscience.net

Yangmei Chen

Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University

Email: info@benthamscience.net

Yuxin Li

Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University

Email: info@benthamscience.net

Xingyu Pan

Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University

Email: info@benthamscience.net

Jin Chen

Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University

Автор, ответственный за переписку.
Email: info@benthamscience.net

Список литературы

  1. Davis, L.E.; Shalin, S.C.; Tackett, A.J. Current state of melanoma diagnosis and treatment. Cancer Biol. Ther., 2019, 20(11), 1366-1379. doi: 10.1080/15384047.2019.1640032 PMID: 31366280
  2. Bomar, L.; Senithilnathan, A.; Ahn, C. Systemic therapies for advanced melanoma. Dermatol. Clin., 2019, 37(4), 409-423. doi: 10.1016/j.det.2019.05.001 PMID: 31466582
  3. Czarnecka, A.M.; Bartnik, E.; Fiedorowicz, M.; Rutkowski, P. Targeted therapy in melanoma and mechanisms of resistance. Int. J. Mol. Sci., 2020, 21(13), 4576. doi: 10.3390/ijms21134576 PMID: 32605090
  4. Namikawa, K.; Yamazaki, N. Targeted therapy and immunotherapy for melanoma in Japan. Curr. Treat. Options Oncol., 2019, 20(1), 7. doi: 10.1007/s11864-019-0607-8 PMID: 30675668
  5. Nasser, M.I.; Zhu, S.; Chen, C.; Zhao, M.; Huang, H.; Zhu, P. A comprehensive review on schisandrin B and its biological properties. Oxid. Med. Cell. Longev., 2020, 2020, 2172740. doi: 10.1155/2020/2172740 PMID: 32256947
  6. Hu, X.L.; Guo, C.; Hou, J.Q.; Feng, J.H.; Zhang, X.Q.; Xiong, F.; Ye, W.C.; Wang, H. Stereoisomers of schisandrin B are potent ATP competitive GSK-3β inhibitors with neuroprotective effects against Alzheimer's Disease: Stereochemistry and biological activity. ACS Chem. Neurosci., 2019, 10(2), 996-1007. doi: 10.1021/acschemneuro.8b00252 PMID: 29944335
  7. Chen, N.; Ko, M. Schisandrin B-induced glutathione antioxidant response and cardioprotection are mediated by reactive oxidant species production in rat hearts. Biol. Pharm. Bull., 2010, 33(5), 825-829. doi: 10.1248/bpb.33.825 PMID: 20460761
  8. Leong, P.K.; Ko, K.M.; Schisandrin, B. A double-edged sword in nonalcoholic fatty liver disease. Oxid. Med. Cell. Longev., 2016, 2016, 6171658. doi: 10.1155/2016/6171658 PMID: 27847552
  9. Yan, C.; Gao, L.; Qiu, X.; Deng, C. Schisandrin B synergizes docetaxel-induced restriction of growth and invasion of cervical cancer cells in vitro and in vivo. Ann. Transl. Med., 2020, 8(18), 1157. doi: 10.21037/atm-20-6109 PMID: 33241006
  10. Ma, R.; Zhan, Y.; Zhang, Y.; Wu, L.; Wang, X.; Guo, M. Schisandrin B ameliorates non-alcoholic liver disease through anti-inflammation activation in diabetic mice. Drug Dev. Res., 2021, ddr.21905 doi: 10.1002/ddr.21905 PMID: 34927282
  11. Wang, Y.; Chen, J.; Huang, Y.; Yang, S.; Tan, T.; Wang, N.; Zhang, J.; Ye, C.; Wei, M.; Luo, J.; Luo, X. Schisandrin B suppresses osteosarcoma lung metastasis in vivo by inhibiting the activation of the Wnt/β catenin and PI3K/Akt signaling pathways. Oncol. Rep., 2022, 47(3), 50. doi: 10.3892/or.2022.8261 PMID: 35029287
  12. He, L.; Chen, H.; Qi, Q.; Wu, N.; Wang, Y.; Chen, M.; Feng, Q.; Dong, B.; Jin, R.; Jiang, L. Schisandrin B suppresses gastric cancer cell growth and enhances the efficacy of chemotherapy drug 5-FU in vitro and in vivo. Eur. J. Pharmacol., 2022, 920, 174823. doi: 10.1016/j.ejphar.2022.174823 PMID: 35157912
  13. Li, Q.; Lu, X.; Wang, C.; Cai, L.; Lu, J.; Wu, J.; Zhuge, Q.; Zheng, W.; Su, Z. Antiproliferative and apoptosis-inducing activity of schisandrin B against human glioma cells. Cancer Cell Int., 2015, 15(1), 12. doi: 10.1186/s12935-015-0160-x PMID: 25685066
  14. Zhao, N.; Su, X.; Li, H.; Li, Z.; Wang, Y.; Chen, J.; Zhuang, W. Schisandrin B inhibits α-melanocyte-stimulating hormone-induced melanogenesis in B16F10 cells via downregulation of MAPK and CREB signaling pathways. Biosci. Biotechnol. Biochem., 2021, 85(4), 834-841. doi: 10.1093/bbb/zbaa100 PMID: 33580697
  15. Samulitis, B.K.; Dorr, R.T.; Chow, H.H. Interaction of dacarbazine and imexon, in vitro and in vivo, in human A375 melanoma cells. Anticancer Res., 2011, 31(9), 2781-2785. PMID: 21868520
  16. Sadhu, S.S.; Wang, S.; Averineni, R.K.; Seefeldt, T.; Yang, Y.; Guan, X. In vitro and in vivo inhibition of melanoma growth and metastasis by the drug combination of celecoxib and dacarbazine. Melanoma Res., 2016, 26(6), 572-579. doi: 10.1097/CMR.0000000000000291 PMID: 27540834
  17. Chanda, M.; Cohen, M.S. Advances in the discovery and development of melanoma drug therapies. Expert Opin. Drug Discov., 2021, 16(11), 1319-1347. doi: 10.1080/17460441.2021.1942834 PMID: 34157926
  18. Olbryt, M. Potential biomarkers of skin melanoma resistance to targeted therapy—present state and perspectives. Cancers, 2022, 14(9), 2315. doi: 10.3390/cancers14092315 PMID: 35565444
  19. Clevers, H.; Nusse, R. Wnt/β-catenin signaling and disease. Cell, 2012, 149(6), 1192-1205. doi: 10.1016/j.cell.2012.05.012 PMID: 22682243
  20. Sun, C.; Wang, L.; Huang, S.; Heynen, G.J.J.E.; Prahallad, A.; Robert, C.; Haanen, J.; Blank, C.; Wesseling, J.; Willems, S.M.; Zecchin, D.; Hobor, S.; Bajpe, P.K.; Lieftink, C.; Mateus, C.; Vagner, S.; Grernrum, W.; Hofland, I.; Schlicker, A.; Wessels, L.F.A.; Beijersbergen, R.L.; Bardelli, A.; Di Nicolantonio, F.; Eggermont, A.M.M.; Bernards, R. Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma. Nature, 2014, 508(7494), 118-122. doi: 10.1038/nature13121 PMID: 24670642
  21. Heinzerling, L.; Eigentler, T.K.; Fluck, M.; Hassel, J.C.; Heller-Schenck, D.; Leipe, J.; Pauschinger, M.; Vogel, A.; Zimmer, L.; Gutzmer, R. Tolerability of BRAF/MEK inhibitor combinations: Adverse event evaluation and management. ESMO Open, 2019, 4(3), e000491. doi: 10.1136/esmoopen-2019-000491 PMID: 31231568
  22. Petrova, V.; Arkhypov, I.; Weber, R.; Groth, C.; Altevogt, P.; Utikal, J.; Umansky, V. Modern aspects of immunotherapy with checkpoint inhibitors in melanoma. Int. J. Mol. Sci., 2020, 21(7), 2367. doi: 10.3390/ijms21072367 PMID: 32235439
  23. Xiang, Y.; Guo, Z.; Zhu, P.; Chen, J.; Huang, Y. Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science. Cancer Med., 2019, 8(5), 1958-1975. doi: 10.1002/cam4.2108 PMID: 30945475
  24. Wang, J.; Wong, Y.K.; Liao, F. What has traditional Chinese medicine delivered for modern medicine? Expert Rev. Mol. Med., 2018, 20, e4. doi: 10.1017/erm.2018.3 PMID: 29747718
  25. Nasser, M.I.; Han, T.; Adlat, S.; Tian, Y.; Jiang, N. Inhibitory effects of Schisandrin B on human prostate cancer cells. Oncol. Rep., 2019, 41(1), 677-685. PMID: 30320364
  26. Dai, X.; Yin, C.; Guo, G.; Zhang, Y.; Zhao, C.; Qian, J.; Wang, O.; Zhang, X.; Liang, G. Schisandrin B exhibits potent anticancer activity in triple negative breast cancer by inhibiting STAT3. Toxicol. Appl. Pharmacol., 2018, 358, 110-119. doi: 10.1016/j.taap.2018.09.005 PMID: 30195018
  27. Wang, S.; Wang, A.; Shao, M.; Lin, L.; Li, P.; Wang, Y. Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin. Sci. Rep., 2017, 7(1), 8419. doi: 10.1038/s41598-017-08817-x PMID: 28827665
  28. Lv, X.J.; Zhao, L.J.; Hao, Y.Q.; Su, Z.Z.; Li, J.Y.; Du, Y.W.; Zhang, J. Schisandrin B inhibits the proliferation of human lung adenocarcinoma A549 cells by inducing cycle arrest and apoptosis. Int. J. Clin. Exp. Med., 2015, 8(5), 6926-6936. PMID: 26221229
  29. Tan, S.; Zheng, Z.; Liu, T.; Yao, X.; Yu, M.; Ji, Y. Schisandrin B induced ROS-mediated autophagy and Th1/Th2 imbalance via Selenoproteins in Hepa1-6 Cells. Front. Immunol., 2022, 13, 857069. doi: 10.3389/fimmu.2022.857069 PMID: 35419003
  30. He, X.R.; Han, S.Y.; Li, X.H.; Zheng, W.X.; Pang, L.N.; Jiang, S.T.; Li, P.P. Chinese medicine Bu-Fei decoction attenuates epithelial-mesenchymal transition of non-small cell lung cancer via inhibition of transforming growth factor β1 signaling pathway in vitro and in vivo. J. Ethnopharmacol., 2017, 204, 45-57. doi: 10.1016/j.jep.2017.04.008 PMID: 28412214

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