Vol 59, No 4 (2021)
Original paper
Published online: 2021-11-30

open access

Page views 7213
Article views/downloads 803
Get Citation

Connect on Social Media

Connect on Social Media

Actinidia chinensis Planch. root extract inhibits the proliferation, migration and invasion of breast cancer cells via the AKT/GSK-3β signaling pathway

Chunchun Gan1, Zhan Jin1, Xiaopeng Wei2, Meina Jin2
Pubmed: 34852177
Folia Histochem Cytobiol 2021;59(4):226-235.

Abstract

Introduction. Actinidia chinensis Planch. root extract (acRoots), known as a traditional Chinese medicine (TCM), has shown antitumor efficacy in various types of human cancers. However, its role and underlying mechanisms in breast cancer (BCa) have not been elucidated.

Material and methods. In the present study, the effects of acRoots on cell viability, apoptosis, migration and invasion were analyzed by MTT assay, colony formation, flow cytometry, wound healing and Transwell assay in MDA-MB-231 and MDA-MB-453 breast cancer cell lines. The expression levels of relevant proteins were determined by Western blot assay.

Results. The results revealed that acRoots inhibited proliferation, migration, and invasion and promoted apoptosis of BCa cells. Moreover, acRoots decreased the expression of cyclin D1, survivin, Bcl-2, N-cadherin, and Snail and increased the expression of Bax and E-cadherin in MDA-MB-231 and MDA-MB-453 cells. AcRoots inhibited the AKT/GSK-3b pathway by decreasing the levels of phosphorylated AKT, phosphorylated GSK-3b and b-catenin.

Conclusions. The described effects of acRoots on the cultured BCa cells suggest that they may be mediated by the inhibition of the AKT/GSK-3b signaling pathway. Thus, further studies are warranted to test the possibility that AcRoots may be used as a promising anticancer agent for breast cancer treatment.

Article available in PDF format

View PDF Download PDF file

References

  1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2): 87–108.
  2. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011; 61(2): 69–90.
  3. Gonzalez-Angulo A, Morales-Vasquez F, Hortobagyi G. Overview of Resistance to Systemic Therapy in Patients with Breast Cancer. Breast Cancer Chemosensitivity. 2007: 1–22.
  4. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012; 490(7418): 61–70.
  5. Sutter SA, Slinker A, Balumuka DD, et al. Surgical Management of Breast Cancer in Africa: A Continent-Wide Review of Intervention Practices, Barriers to Care, and Adjuvant Therapy. J Glob Oncol. 2017; 3(2): 162–168.
  6. Caetano-Pinto P, Jansen J, Assaraf YG, et al. The importance of breast cancer resistance protein to the kidneys excretory function and chemotherapeutic resistance. Drug Resist Updat. 2017; 30: 15–27.
  7. Tao Z, Shi A, Lu C, et al. Breast Cancer: Epidemiology and Etiology. Cell Biochem Biophys. 2015; 72(2): 333–338.
  8. Miller AB, Bulbrook RD. The epidemiology and etiology of breast cancer. N Engl J Med. 1980; 303(21): 1246–1248.
  9. Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol. 2005; 100(1-2): 72–79.
  10. Buyel JF. Plants as sources of natural and recombinant anti-cancer agents. Biotechnol Adv. 2018; 36(2): 506–520.
  11. Mitra S, Dash R. Natural Products for the Management and Prevention of Breast Cancer. Evid Based Complement Alternat Med. 2018; 2018: 8324696.
  12. Sun L, Li X, Li G, et al. Actinidia chinensis Planch. Improves the Indices of Antioxidant and Anti-Inflammation Status of Type 2 Diabetes Mellitus by Activating Keap1 and Nrf2 via the Upregulation of MicroRNA-424. Oxid Med Cell Longev. 2017; 2017: 1–14.
  13. Zhu WJ, Yu DH, Zhao M, et al. Antiangiogenic triterpenes isolated from Chinese herbal medicine Actinidia chinensis Planch. Anticancer Agents Med Chem. 2013; 13(2): 195–198.
  14. Zhang L, Zhang W, Wang Q, et al. Purification, antioxidant and immunological activities of polysaccharides from Actinidia Chinensis roots. Int J Biol Macromol. 2015; 72: 975–983.
  15. Hou J, Wang L, Wu D. The root of Actinidia chinensis inhibits hepatocellular carcinomas cells through LAMB3. Cell Biol Toxicol. 2018; 34(4): 321–332.
  16. Fang T, Hou J, He M, et al. Actinidia chinensis Planch root extract (acRoots) inhibits hepatocellular carcinoma progression by inhibiting EP3 expression. Cell Biol Toxicol. 2016; 32(6): 499–511.
  17. Fang T, Fang Y, Xu X, et al. Actinidia chinensis Planch root extract attenuates proliferation and metastasis of hepatocellular carcinoma by inhibiting epithelial-mesenchymal transition. J Ethnopharmacol. 2019; 231: 474–485.
  18. He M, Hou J, Wang L, et al. Actinidia chinensis Planch root extract inhibits cholesterol metabolism in hepatocellular carcinoma through upregulation of PCSK9. Oncotarget. 2017; 8(26): 42136–42148.
  19. Huo J, Qin F, Cai X, et al. Chinese medicine formula "Weikang Keli" induces autophagic cell death on human gastric cancer cell line SGC-7901. Phytomedicine. 2013; 20(2): 159–165.
  20. Deng S, Hu B, An HM, et al. Teng-Long-Bu-Zhong-Tang, a Chinese herbal formula, enhances anticancer effects of 5--Fluorouracil in CT26 colon carcinoma. BMC Complement Altern Med. 2013; 13: 128.
  21. Cheng QL, Li HL, Huang ZQ, et al. 2β, 3β, 23-trihydroxy-urs-12-ene-28-olic acid (TUA) isolated from Actinidia chinensis Radix inhibits NCI-H460 cell proliferation by decreasing NF-κB expression. Chem Biol Interact. 2015; 240: 1–11.
  22. Varankar SS, Bapat SA. Migratory Metrics of Wound Healing: A Quantification Approach for Scratch Assays. Front Oncol. 2018; 8: 633.
  23. Sun L, Jin X, Xie L, et al. Swainsonine represses glioma cell proliferation, migration and invasion by reduction of miR-92a expression. BMC Cancer. 2019; 19(1): 247.
  24. Wang Z, Li TE, Chen Mo, et al. miR-106b-5p contributes to the lung metastasis of breast cancer via targeting CNN1 and regulating Rho/ROCK1 pathway. Aging (Albany NY). 2020; 12(2): 1867–1887.
  25. Son YO, Wang L, Poyil P, et al. Cadmium induces carcinogenesis in BEAS-2B cells through ROS-dependent activation of PI3K/AKT/GSK-3β/β-catenin signaling. Toxicol Appl Pharmacol. 2012; 264(2): 153–160.
  26. Zhou SL, Zhou ZJ, Hu ZQ, et al. CXCR2/CXCL5 axis contributes to epithelial-mesenchymal transition of HCC cells through activating PI3K/Akt/GSK-3β/Snail signaling. Cancer Lett. 2015; 358(2): 124–135.
  27. Chen Q, Yang D, Zong H, et al. Growth-induced stress enhances epithelial-mesenchymal transition induced by IL-6 in clear cell renal cell carcinoma via the Akt/GSK-3β/β-catenin signaling pathway. Oncogenesis. 2017; 6(8): e375.
  28. Liu J, Chen Y, Shuai S, et al. TRPM8 promotes aggressiveness of breast cancer cells by regulating EMT via activating AKT/GSK-3β pathway. Tumour Biol. 2014; 35(9): 8969–8977.
  29. Ye X, Guo Yu, Zhang Qi, et al. βKlotho suppresses tumor growth in hepatocellular carcinoma by regulating Akt/GSK-3β/cyclin D1 signaling pathway. PLoS One. 2013; 8(1): e55615.
  30. Lu J, Steeg PS, Price JE, et al. Breast cancer metastasis: challenges and opportunities. Cancer Res. 2009; 69(12): 4951–4953.
  31. Cohen I, Tagliaferri M, Tripathy D. Traditional Chinese medicine in the treatment of breast cancer. Semin Oncol. 2002; 29(6): 563–574.
  32. Cui Y, Shu XO, Gao Y, et al. Use of complementary and alternative medicine by Chinese women with breast cancer. Breast Cancer Research and Treatment. 2004; 85(3): 263–270.
  33. Koff JL, Ramachandiran S, Bernal-Mizrachi L. A time to kill: targeting apoptosis in cancer. Int J Mol Sci. 2015; 16(2): 2942–2955.
  34. Gao Z, Deng G, Li Y, et al. Actinidia chinensis Planch prevents proliferation and migration of gastric cancer associated with apoptosis, ferroptosis activation and mesenchymal phenotype suppression. Biomed Pharmacother. 2020; 126: 110092.
  35. Ye X, Brabletz T, Kang Y, et al. Upholding a role for EMT in breast cancer metastasis. Nature. 2017; 547(7661): E1–E3.
  36. Gunasinghe NP, Wells A, Thompson EW, et al. Mesenchymal-epithelial transition (MET) as a mechanism for metastatic colonisation in breast cancer. Cancer Metastasis Rev. 2012; 31(3-4): 469–478.
  37. Wang Y, Shi J, Chai K, et al. The Role of Snail in EMT and Tumorigenesis. Curr Cancer Drug Targets. 2013; 13(9): 963–972.
  38. Berx G, Van Roy F. The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression. Breast Cancer Res. 2001; 3(5): 289–293.
  39. Mrozik KM, Blaschuk OW, Cheong CM, et al. N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer. BMC Cancer. 2018; 18(1): 939.
  40. Lv J, Wang L, Shen H, et al. Regulatory roles of OASL in lung cancer cell sensitivity to Actinidia chinensis Planch root extract (acRoots). Cell Biol Toxicol. 2018; 34(3): 207–218.
  41. Wang Q, Xu Y, Gao Y, et al. Actinidia�chinensis planch polysaccharide protects against hypoxia‑induced apoptosis of cardiomyocytes in�vitro. Molecular Medicine Reports. 2018.
  42. Cohen P, Frame S. The renaissance of GSK3. Nat Rev Mol Cell Biol. 2001; 2(10): 769–776.
  43. Sharma M, Chuang WW, Sun Z. Phosphatidylinositol 3-kinase/Akt stimulates androgen pathway through GSK3beta inhibition and nuclear beta-catenin accumulation. J Biol Chem. 2002; 277(34): 30935–30941.
  44. MacDonald BT, Tamai K, He Xi. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009; 17(1): 9–26.
  45. Li D, Beisswenger C, Herr C, et al. Myeloid cell RelA/p65 promotes lung cancer proliferation through Wnt/β-catenin signaling in murine and human tumor cells. Oncogene. 2014; 33(10): 1239–1248.
  46. Qu T, Zhao Y, Chen Y, et al. Down-regulated MAC30 expression inhibits breast cancer cell invasion and EMT by suppressing Wnt/β-catenin and PI3K/Akt signaling pathways . Int J Clin Exp Pathol. 2019 ; 12(5): 1888–1896.