Skip to content
2000
image of The Effects of Rukangyin on the Biological Behavior and Hippo Signaling Pathway in MDA-MB-231 Breast Cancer Cells

Abstract

Introduction

This study aims to examine the impact of Rukangyin (RKY) and its components, LSQR and QTSS, on various cellular processes and signaling mechanisms in MDA-MB-231 triple-negative breast cancer (TNBC) cells.

Methods

Twenty-five Sprague-Dawley (SD) rats were randomly assigned to five groups according to the administered drugs, including the RKY group, LSQR group, QTSS group, fluorouracil group, and blank control group (n=5 in each group). The serum samples from each group were then used as a medicated medium for the culture of the TNBC cell line MDA-MB-231. Cell viability tests, apoptosis detection tests, and migration and invasion tests were used to evaluate the cytotoxicity of treated serum. YAP, TAZ, MST1, and LATS1 protein expression and phosphorylation were examined using conventional western blotting methods.

Results

RKY and its QTSS and LSQR components significantly inhibited cell growth and promoted apoptosis in MDA-MB-231 cells. RKY also significantly blocked cell motility with a comparable effect to that of fluorouracil. All serum groups suppressed YAP and TAZ expressions while increasing p-YAP, p-TAZ, MST1, and LATS1 levels, with RKY showing superior efficacy.

Discussion

In TNBC cells, RKY appears to enhance the tumor-suppressing signals of the Hippo signaling pathway via MST1, LATS1 activation, while restricting its pro-oncogenic action via YAP and TAZ blockade. However, and animal model experiments are required to confirm these findings.

Conclusion

RKY-medicated serum effectively inhibits growth, induces apoptosis, and reduces motility in the MDA-MB-231 cell line of breast cancer. This therapeutic potential of RKY on TNBC cells draws attention to the need for more investigations.

Loading

Article metrics loading...

/content/journals/cpb/10.2174/0113892010402625250730085430
2025-08-06
2025-12-19
Loading full text...

Full text loading...

References

  1. Ginsburg O. Bray F. Coleman M.P. Vanderpuye V. Eniu A. Kotha S.R. Sarker M. Huong T.T. Allemani C. Dvaladze A. Gralow J. Yeates K. Taylor C. Oomman N. Krishnan S. Sullivan R. Kombe D. Blas M.M. Parham G. Kassami N. Conteh L. The global burden of women’s cancers: a grand challenge in global health. Lancet 2017 389 10071 847 860 10.1016/S0140‑6736(16)31392‑7 27814965
    [Google Scholar]
  2. Zeng Q. Chen C. Chen C. Song H. Li M. Yan J. Lv X. Serum Raman spectroscopy combined with convolutional neural network for rapid diagnosis of HER2-positive and triple-negative breast cancer. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2023 286 122000 10.1016/j.saa.2022.122000 36279798
    [Google Scholar]
  3. Ma X. Cheng H. Hou J. Jia Z. Wu G. Lü X. Li H. Zheng X. Chen C. Detection of breast cancer based on novel porous silicon Bragg reflector surface-enhanced Raman spectroscopy-active structure. Chin. Opt. Lett. 2020 18 5 051701 10.3788/COL202018.051701
    [Google Scholar]
  4. Chen J. Chen Q. Xiao P. Jin W. Yu L. A novel framework for uncovering the coordinative spectrum-effect correlation of the effective components of Yangyin Tongnao Granules on cerebral ischemia-reperfusion injury in rats. J. Ethnopharmacol. 2025 337 Pt 1 118844 10.1016/j.jep.2024.118844 39303966
    [Google Scholar]
  5. Turanli B. Karagoz K. Gulfidan G. Sinha R. Mardinoglu A. Arga K.Y. A network-based cancer drug discovery: From integrated multi-omics approaches to precision medicine. Curr. Pharm. Des. 2019 24 32 3778 3790 10.2174/1381612824666181106095959 30398107
    [Google Scholar]
  6. Poornima P. Kumar J.D. Zhao Q. Blunder M. Efferth T. Network pharmacology of cancer: From understanding of complex interactomes to the design of multi-target specific therapeutics from nature. Pharmacol. Res. 2016 111 290 302 10.1016/j.phrs.2016.06.018 27329331
    [Google Scholar]
  7. Liu C. Wang K. Zhuang J. Gao C. Li H. Liu L. Feng F. Zhou C. Yao K. Deng L. Wang L. Li J. Sun C. The modulatory properties of Astragalus membranaceus treatment on triple-negative breast cancer: An integrated pharmacological method. Front. Pharmacol. 2019 10 1171 10.3389/fphar.2019.01171 31680955
    [Google Scholar]
  8. Wang N. Yang B. Zhang X. Wang S. Zheng Y. Li X. Liu S. Pan H. Li Y. Huang Z. Zhang F. Wang Z. Network pharmacology-based validation of caveolin-1 as a Key Mediator of Ai Du Qing inhibition of drug resistance in breast cancer. Front. Pharmacol. 2018 9 1106 10.3389/fphar.2018.01106 30333750
    [Google Scholar]
  9. Park M. Kim D. Ko S. Kim A. Mo K. Yoon H. Breast cancer metastasis: Mechanisms and therapeutic implications. Int. J. Mol. Sci. 2022 23 12 6806 10.3390/ijms23126806 35743249
    [Google Scholar]
  10. Driskill J.H. Pan D. The hippo pathway in liver homeostasis and pathophysiology. Annu. Rev. Pathol. 2021 16 1 299 322 10.1146/annurev‑pathol‑030420‑105050 33234023
    [Google Scholar]
  11. Nguyen C.D.K. Yi C. YAP/TAZ signaling and resistance to cancer therapy. Trends Cancer 2019 5 5 283 296 10.1016/j.trecan.2019.02.010 31174841
    [Google Scholar]
  12. Pobbati A.V. Hong W. A combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy. Theranostics 2020 10 8 3622 3635 10.7150/thno.40889 32206112
    [Google Scholar]
  13. Vlug E.J. van de Ven R.A.H. Vermeulen J.F. Bult P. van Diest P.J. Derksen P.W.B. Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer. Cell Oncol. (Dordr.) 2013 36 5 375 384 10.1007/s13402‑013‑0143‑7 23949920
    [Google Scholar]
  14. Heidary Arash E. Shiban A. Song S. Attisano L. MARK4 inhibits Hippo signaling to promote proliferation and migration of breast cancer cells. EMBO Rep. 2017 18 3 420 436 10.15252/embr.201642455 28183853
    [Google Scholar]
  15. Zeichner S.B. Terawaki H. Gogineni K. A Review of systemic treatment in metastatic triple-negative breast cancer. Breast Cancer (Auckl) 2016 10 BCBCR.S32783 10.4137/BCBCR.S32783 27042088
    [Google Scholar]
  16. Mirzania M. Safaee S.R. Shahi F. Jahanzad I. Zahedi G. Mehdizadeh R. Treatment outcomes and clinicopathologic characteristics of triple-negative breast cancer: A report from cancer Institute of Iran. Int. J. Hematol. Oncol. Stem Cell Res. 2017 11 1 37 42 28286613
    [Google Scholar]
  17. Cha Y.J. Bae S.J. Kim D. Ahn S.G. Jeong J. Koo J.S. Yoo T.K. Park W.C. Lee A. Yoon C.I. High nuclear expression of yes-associated protein 1 correlates with metastasis in patients with breast cancer. Front. Oncol. 2021 11 609743 10.3389/fonc.2021.609743 33718163
    [Google Scholar]
  18. Yang S. Sun S. Xu W. Yu B. Wang G. Wang H. Astragalus polysaccharide inhibits breast cancer cell migration and invasion by regulating epithelial mesenchymal transition via the Wnt/β catenin signaling pathway. Mol. Med. Rep. 2020 21 4 1819 1832 10.3892/mmr.2020.10983 32319619
    [Google Scholar]
  19. Dong N. Li X. Xue C. Zhang L. Wang C. Xu X. Shan A. Astragalus polysaccharides alleviates LPS‐induced inflammation via the NF‐κB/MAPK signaling pathway. J. Cell. Physiol. 2020 235 7-8 5525 5540 10.1002/jcp.29452 32037545
    [Google Scholar]
  20. Li X. Ma L. Zhang L. Molecular basis for Poria cocos mushroom polysaccharide used as an antitumor drug in China. Prog. Mol. Biol. Transl. Sci. 2019 163 263 296 10.1016/bs.pmbts.2019.02.011 31030751
    [Google Scholar]
  21. Qu D. Liu M. Huang M. Wang L. Chen Y. Liu C. Liu Y. Octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components to enhance tumor targeting and hepatoma therapy. Int. J. Nanomedicine 2017 12 2045 2059 10.2147/IJN.S125293 28352174
    [Google Scholar]
  22. Feng L. Liu L. Zhao Y. Zhao R. Saikosaponins A. C and D enhance liver-targeting effects of anticancer drugs by modulating drug transporters. Oncotarget 2017 8 66 110092 110102 10.18632/oncotarget.22639 29299132
    [Google Scholar]
  23. Lee C.J. Wilson L. Jordan M.A. Nguyen V. Tang J. Smiyun G. Hesperidin suppressed proliferations of both Human breast cancer and androgen‐dependent prostate cancer cells. Phytother Res. 2010 24 S1 S15 S19.(Suppl. 1) 10.1002/ptr.2856 19548283
    [Google Scholar]
  24. Li W. Hu X. Li Y. Song K. Cytotoxicity and growth-inhibiting activity of Astragalus polysaccharides against breast cancer via the regulation of EGFR and ANXA1. J. Nat. Med. 2021 75 4 854 870 10.1007/s11418‑021‑01525‑x 34043154
    [Google Scholar]
  25. Nandakumar N. Rengarajan T. Balamurugan A. Balasubramanian M.P. Modulating effects of hesperidin on key carbohydrate-metabolizing enzymes, lipid profile, and membrane-bound adenosine triphosphatases against 7,12-dimethylbenz(a)anthracene-induced breast carcinogenesis. Hum. Exp. Toxicol. 2014 33 5 504 516 10.1177/0960327113485252 23690228
    [Google Scholar]
  26. Liu C. Li H. Wang K. Zhuang J. Chu F. Gao C. Liu L. Feng F. Zhou C. Zhang W. Sun C. Identifying the antiproliferative effect of Astragalus polysaccharides on breast cancer: Coupling network pharmacology with targetable screening from the cancer genome atlas. Front. Oncol. 2019 9 368 10.3389/fonc.2019.00368 31157164
    [Google Scholar]
  27. Zhao M. Yang C. Chai S. Yuan Y. Zhang J. Cao P. Wang Y. Xiao X. Wu K. Yan H. Liu J. Sun S. Curcumol and FTY720 synergistically induce apoptosis and differentiation in chronic myelomonocytic leukemia via multiple signaling pathways. Phytother. Res. 2021 35 4 2157 2170 10.1002/ptr.6968 33274566
    [Google Scholar]
  28. Wei C. Wang Y. Li X. The role of Hippo signal pathway in breast cancer metastasis. OncoTargets Ther. 2018 11 2185 2193 10.2147/OTT.S157058 29713187
    [Google Scholar]
  29. Kulkarni A. Chang M.T. Vissers J.H.A. Dey A. Harvey K.F. The hippo pathway as a driver of select human cancers. Trends Cancer 2020 6 9 781 796 10.1016/j.trecan.2020.04.004 32446746
    [Google Scholar]
  30. Sharma P. Hu-Lieskovan S. Wargo J.A. Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 2017 168 4 707 723 10.1016/j.cell.2017.01.017 28187290
    [Google Scholar]
  31. Nguyen Q.P. Deng T.Z. Witherden D.A. Goldrath A.W. Origins of CD 4 + circulating and tissue‐resident memory T‐cells. Immunology 2019 157 1 3 12 10.1111/imm.13059 30897205
    [Google Scholar]
  32. Yamamoto N. Nokihara H. Yamada Y. Shibata T. Tamura Y. Seki Y. Honda K. Tanabe Y. Wakui H. Tamura T. Phase I study of Nivolumab, an anti-PD-1 antibody, in patients with malignant solid tumors. Invest. New Drugs 2017 35 2 207 216 10.1007/s10637‑016‑0411‑2 27928714
    [Google Scholar]
  33. Parambil S.T. Antony G.R. Littleflower A.B. Subhadradevi L. The molecular crosstalk of the hippo cascade in breast cancer: A potential central susceptibility. Biochimie 2024 222 132 150 10.1016/j.biochi.2024.03.008 38494109
    [Google Scholar]
  34. Dehghanian F. Ghahnavieh L.E. Nilchi A.N. Khalilian S. Joonbakhsh R. Breast cancer drug resistance: Decoding the roles of Hippo pathway crosstalk. Gene 2024 916 148424 10.1016/j.gene.2024.148424 38588933
    [Google Scholar]
  35. Qin Q. Niu J. Wang Z. Xu W. Qiao Z. Gu Y. Astragalus membranaceus inhibits inflammation via phospho-P38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB pathways in advanced glycation end product-stimulated macrophages. Int. J. Mol. Sci. 2012 13 7 8379 8387 10.3390/ijms13078379 22942709
    [Google Scholar]
  36. Chu S. Network pharmacology reveals hub bio-active ingredients and possible mechanisms of a Chinese herbal prescription Ru-kang-yin against breast cancer. Research Square 2020 10.21203/rs.3.rs‑69347/v1
    [Google Scholar]
/content/journals/cpb/10.2174/0113892010402625250730085430
Loading
/content/journals/cpb/10.2174/0113892010402625250730085430
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keywords: rukangyin ; hippo signaling pathway ; Apoptosis ; protein phosphorylation ; breast cancer
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test