Baicalein regulates Rho-ROCK-MLC pathway to inhibit the growth and metastasis of breast cancer

CAI Fei-fei1 WANG Xiu-feng1 ZHOU Qian-mei1 LU Yi-yu1 SU Shi-bing1

(1.Research Center for Traditional Chinese Medicine Complexity System, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203)
【Novelty】In recent years, baicalein has received increasing attention for its ability to inhibit the proliferation of tumor cells or induce apoptosis and autophagic cell death in low toxicity cancer cells, especially for its ability to inhibit metastasis in breast cancer . Abnormal activation of RhoA and ROCK in breast cancer tissues causes enhanced phosphorylation of downstream MLC, leading to migration and invasion of cancer cells. The aim of this study was to observe the inhibitory effect of baicalein on the growth and metastasis of human breast cancer xenograft tumor in nude mice, and explore the mechanism of baicalein participating in ROCK mediated cytoskeleton recombination and inhibiting the migration of human breast cancer MDA-MB-231 cells.

【Abstract】In this study, the inhibitory effect and mechanism of baicalein on tumor growth and lung metastasis of human breast cancer MDA-MB-231cells in nude mice was investigated. Twenty female BALB/C nude mice were randomized into normal group, model group, paclitaxel group, and baicalein group, with five mice in each group. The nude mice model of human breast cancer xenograft was established. Baicalein group was injected with 50 mg/kg baicalein, paclitaxel group 10 mg/kg paclitaxel, and normal group and model group normal saline for 8 weeks. Experimental results indicated that the tumor weight and the number lung metastatic nodules and metastases in paclitaxel group and baicalein group were smaller than those in the model group. Baicalein alone or in combination with ROCK inhibitor Y-27632 can inhibit the migration and cytoskeleton protein expression of MDA-MB-231 cells, reduce the formation of protein bundles, and inhibit the protein levels of ROCK1, Rac1, RhoA, and p-MLC.

【Keywords】 baicalein; breast cancer; cell migration;

【DOI】

【Funds】 Key Project of National Natural Science Foundation of China (81330084)

Download this article

    References

    1 Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012 [J]. CA Cancer J Clin, 2015, 65 (2): 87–108.

    2 Li L, Jiang SH. Experimental research progress of Chinese medicine intervention on breast cancer [J]. Tradit Chin Med Res, 2015, 28 (4): 71–73.

    3 Bie B, Sun J, Guo Y, et al. Baicalein: A review of its anti-cancer effect and mechanisms in hepatocellular carcinoma [J]. Biomed Pharmacother, 2017, 93: 1285–1291.

    4 Wu JY, Tsai KW, Li YZ, et al. Anti-bladder-tumor effect of baicalein from Scutellaria baicalensis Georgi and its application in vivo [J]. Evid-based Compl Alt, 2013, 2013: 579751.

    5 Yan WJ, Zhang SQ. Inhibition mechanism of baicalein on the liver metastasis of breast cancer cell in vivo [J]. Pract J Cancer, 2018, 33 (12): 5–9.

    6 Yan WJ, Ma XC, Gao XY, et al. Research progress in the correlation between baicalein and the invasion and metastasis of breast cancer [J]. J Mod Oncol, 2016, 24: 491–494.

    7 Voorneveld PW, Kodach LL, Jacobs RJ, et al. Loss of SMAD4 alters BMP signaling to promote colorectal cancer cell metastasis via activation of Rho and ROCK [J]. Gastroenterology, 2014, 147: 196–208.

    8 Qi RF, Shi RL, Lv J, et al. Curcumin combined with paclitaxel can reduce breast cancer MDA-MB-231 cell migration synergistically and reduce MMP9 expression in vitro and in vivo [J]. Pharmacol Clin Chin Mater Med, 2016, 32 (1): 83–85.

    9 Rui X, Yan XI, Zhang K. Baicalein inhibits the migration and invasion of colorectal cancer cells via suppression of the AKT signaling pathway [J]. Oncol Lett, 2016, 11 (1): 685.

    10 Guo J, You H, Li D. Baicalein exerts anticancer effect in nasopharyngeal carcinoma in vitro and in vivo [J]. Oncol Res Featur Preclin Clin Cancer Ther, 2019, 27: 601–611.

    11 Chen DH, Deng YR, Mou JJ, et al. Structural modification and antitumor activity of baicalein [J]. Nat Prod Res Dev, 2019, 31: 1258–1264.

    12 Wang XF, Zhou QM, Su SB, et al. Experimental study on the inhibition of baicalein on invasion and migration of human breast cancer cells [J]. Chin Pharmacol Bull, 2010, 26: 745–750.

    13 Yan WJ, Ma XC, Gao XY, et al. Inhibition mechanism of baicalein on the lung metastasis of breast cancer cell in vivo [J]. J Cancer Control Treat, 2015, 28: 310–316.

    14 Yang R, Li Z, Li ZY, et al. Macrophage colony stimulating factor mediates macrophage migration in triple negative breast cancer through RhoA/ROCK signaling pathway [J]. Chin Remed Clin, 2019, 19: 1786–1788.

    15 Geiger B, Zaidel-Bar R, Rao MV. The molecular architecture of cell-cell adhesions [J]. Encycl Cell Biol, 2016: 181–191.

    16 Gao ML, Lin ZH, Xu YJ, et al. Effect of baicalein on proliferation and migration of breast cancer cell MDA-MB-231 in vitro [J]. Lishizhen Med Mater Med Res, 2013, 24: 1389–1390.

    17 Rosenthal DT, Iyer H, Escudero S, et al. p38γ promotes breast cancer cell motility and metastasis through regulation of RhoC GTPase, cytoskeletal architecture, and a novel leading edge behavior [J]. Cancer Res, 2011, 71: 6338–6349.

    18 Xiang RF, Stack D, Huston SM, et al. Ras-related C3 botulinum toxin substrate (Rac) and Src family kinases (SFK) are proximal and essential for phosphatidylinositol 3-kinase (PI3K) activation in natural killer (NK) cell-mediated direct cytotoxicity against cryptococcus neoformans [J]. J Biol Chem, 2016, 291: 6912–6922.

    19 Ridley AJ. Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking [J]. Trends Cell Biol, 2006, 16: 522–529.

    20 Hahmann C, Schroeter T. Rho-kinase inhibitors as therapeutics: from pan inhibition to isoform selectivity [J]. Cell Mol Life Sci, 2010, 67: 171–177.

    21 Riento K, Ridley AJ. Rocks: multifunctional kinases in cell behaviour [J]. Nat Rev Mol Cell Biol, 2003, 4: 446–456.

    22 Gao J, Su XB, Lin SY, et al. Inhibitory effect of Kiss-1 gene on metastatis of HCT116 human colorectal carcinoma cells via down-regulating mitogen activated protein kinase signal transduction pathway [J]. Chin J Exp Surg, 2016, 33: 1988–1992.

This Article

ISSN:1001-6880

CN:51-1335/Q

Vol 33, No. 04, Pages 570-576

April 2021

Downloads:10

Share
Article Outline

Novelty

Abstract

  • 1 Materials
  • 2 Methods
  • 3 Results
  • 4 Discussion
  • References