Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Ethyl Acetate Fraction from Hedyotis Diffusa Plus Scutellaria Barbata Inhibits the Progression of Breast Cancer via Targeting LMO1 and AKT/Mtor Signaling Pathway

Author(s): Zhiyuan Li, Jingwei Li, Xiaofei Liu, Ziyuan Sun and Xiaohui Sun*

Volume 27, Issue 12, 2024

Published on: 21 November, 2023

Page: [1735 - 1744] Pages: 10

DOI: 10.2174/1386207326666230913105858

Price: $65

Abstract

Background: Traditional Chinese medicines are widely used in cancer treatment. Scutellaria barbata and Hedyotis diffusa herb pair (SH) has an anticancer effects in various tumors. However, the specific mechanism of SH in breast cancer remains unclear.

Methods: In the present research, we investigated the effect and regulatory network of SH in in breast cancer. CCK8, colony formation, transwell, wound healing and flow cytometry analysis were used for the detection of cell function.

Results: Ethyl acetate fraction from SH at an equal weight ratio (EA11) could inhibit the proliferation, migration and invasion of MCF7 and MDA-MB-231 cells. It also induced apoptosis in these two cell lines by downregulating Bcl2 and upregulating Bax and Cleaved-Caspase3. SH reduced the activation of the AKT/mTOR signaling pathway and the expression of p70S6K. Sequencing results showed that LMO1 was significantly downregulated in SH-treated cells compared with control cells. Importantly, overexpression of LMO1 attenuated the inhibitory effect of SH on cell proliferation and invasion and induced inflammatory tumor microenvironment.

Conclusion: In conclusion, the SH herb pair inhibited the proliferation and metastasis through downregulating LMO1 expression and reducing the activation of the AKT/mTOR signaling pathway. LMO1 has the potential as a new target in the treatment of breast cancer.

« Previous Next »
Graphical Abstract

[1]
Anastasiadi, Z.; Lianos, G.D.; Ignatiadou, E.; Harissis, H.V.; Mitsis, M. Breast cancer in young women: An overview. Updates Surg., 2017, 69(3), 313-317.
[http://dx.doi.org/10.1007/s13304-017-0424-1] [PMID: 28260181]
[2]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[3]
Fahad Ullah, M. Breast Cancer: Current Perspectives on the Disease Status. Adv. Exp. Med. Biol., 2019, 1152, 51-64.
[http://dx.doi.org/10.1007/978-3-030-20301-6_4] [PMID: 31456179]
[4]
Liu, Y.T.; Hsiao, C.H.; Tzang, B.S.; Hsu, T.C. In vitro and in vivo effects of traditional Chinese medicine formula T33 in human breast cancer cells. BMC Complement. Altern. Med., 2019, 19(1), 211.
[http://dx.doi.org/10.1186/s12906-019-2630-5] [PMID: 31409331]
[5]
Huang, C.H.; Chang, H.P.; Su, S.Y.; Chen, W.K.; Chang, Y.J.; Lee, Y.C.; Kuo, Y.J. Traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment. J. Ethnopharmacol., 2019, 229, 15-21.
[http://dx.doi.org/10.1016/j.jep.2018.09.030] [PMID: 30261193]
[6]
Chan, P.W.; Chiu, J.H.; Huang, N.; Chen, C.M.; Yu, H.; Liu, C.Y.; Hsu, C.H. Influence of traditional chinese medicine on medical adherence and outcome in estrogen receptor (+) breast cancer patients in taiwan: A real-world population-based cohort study. Phytomedicine, 2021, 80, 153365.
[http://dx.doi.org/10.1016/j.phymed.2020.153365] [PMID: 33126168]
[7]
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.
[http://dx.doi.org/10.1002/cam4.2108] [PMID: 30945475]
[8]
Yan, Z.; Lai, Z.; Lin, J. Anticancer Properties of Traditional Chinese Medicine. Comb. Chem. High Throughput Screen., 2017, 20(5), 423-429.
[http://dx.doi.org/10.2174/1386207320666170116141818] [PMID: 28093974]
[9]
Kalaiarasi, A.; Anusha, C.; Sankar, R.; Rajasekaran, S.; John Marshal, J.; Muthusamy, K.; Ravikumar, V. Plant Isoquinoline Alkaloid Berberine Exhibits Chromatin Remodeling by Modulation of Histone Deacetylase To Induce Growth Arrest and Apoptosis in the A549 Cell Line. J. Agric. Food Chem., 2016, 64(50), 9542-9550.
[http://dx.doi.org/10.1021/acs.jafc.6b04453] [PMID: 27936791]
[10]
Chandrashekar, N.; Pandi, A. Baicalein: A review on its anti‐cancer effects and mechanisms in lung carcinoma. J. Food Biochem., 2022, 46(9), e14230.
[http://dx.doi.org/10.1111/jfbc.14230] [PMID: 35543192]
[11]
Zhang, H.; Zhou, F.; Wang, Y.; Xie, H.; Luo, S.; Meng, L.; Su, B.; Ye, Y.; Wu, K.; Xu, Y.; Gong, X. Eliminating Radiation Resistance of Non-Small Cell Lung Cancer by Dihydroartemisinin Through Abrogating Immunity Escaping and Promoting Radiation Sensitivity by Inhibiting PD-L1 Expression. Front. Oncol., 2020, 10, 595466.
[http://dx.doi.org/10.3389/fonc.2020.595466] [PMID: 33194761]
[12]
Xu, J.; Pan, Y.; Liu, Y.; Na, S.; Zhou, H.; Li, L.; Chen, F.; Song, H. A review of anti-tumour effects of ginsenoside in gastrointestinal cancer. J. Pharm. Pharmacol., 2021, 73(10), 1292-1301.
[http://dx.doi.org/10.1093/jpp/rgab048] [PMID: 33836068]
[13]
Chen, Q.; Rahman, K.; Wang, S.J.; Zhou, S.; Zhang, H. Scutellaria barbata: A review on chemical constituents, pharmacological activities and clinical applications. Curr. Pharm. Des., 2020, 26(1), 160-175.
[http://dx.doi.org/10.2174/1381612825666191216124310] [PMID: 31840605]
[14]
Chen, R.; He, J.; Tong, X.; Tang, L.; Liu, M. The hedyotis diffusa willd. (Rubiaceae): A review on phytochemistry, pharmacology, quality control and pharmacokinetics. Molecules, 2016, 21(6), 710.
[http://dx.doi.org/10.3390/molecules21060710] [PMID: 27248992]
[15]
Yeh, Y.C.; Chen, H.Y.; Yang, S.H.; Lin, Y.H.; Chiu, J.H.; Lin, Y.H. Hedyotis diffusa combined with scutellaria barbata are the core treatment of chinese herbal medicine used for breast cancer patients: A population-based study. Evid. Based Complement. Alternat. Med., 2014, 2014, 202378.
[http://dx.doi.org/10.1155/2014/202378] [PMID: 24734104]
[16]
Pan, L.T.; Sheung, Y.; Guo, W.P.; Rong, Z.B.; Cai, Z.M. Hedyotis diffusa plus Scutellaria barbata Induce Bladder Cancer Cell Apoptosis by Inhibiting Akt Signaling Pathway through Downregulating miR-155 Expression. Evid. Based Complement. Alternat. Med., 2016, 2016, 9174903.
[http://dx.doi.org/10.1155/2016/9174903] [PMID: 26989427]
[17]
Fang, T.; Yan, Y.X.; Yang, Y.; Lv, Y.X.; Chang, Q.Q.; Zhang, D.D. Ethyl Acetate Fraction from Hedyotis diffusa plus Scutellaria barbata Suppresses Migration of Bone-Metastatic Breast Cancer Cells via OPN-FAK/ERK/NF- κ B Axis. Evid. Based Complement. Alternat. Med., 2020, 2020, 3573240.
[http://dx.doi.org/10.1155/2020/3573240] [PMID: 32351594 ]
[18]
Yang, Y.; Fang, T.; Cao, Y.L.; Lv, Y.X.; Chang, Q.Q.; Zhang, D.D. Ethyl Acetate Fraction from Hedyotis diffusa plus Scutellaria barbata Exerts Anti-Breast Cancer Effect via miR-200c-PDE7B/PD-L1-AKT/MAPK Axis. Evid. Based Complement. Alternat. Med., 2020, 2020, 3587095.
[http://dx.doi.org/10.1155/2020/3587095] [PMID: 32922506]
[19]
Ma, T.T.; Zhang, G.L.; Dai, C.F.; Zhang, B.R.; Cao, K.X.; Wang, C.G.; Yang, G.W.; Wang, X.M. Scutellaria barbata and Hedyotis diffusa herb pair for breast cancer treatment: Potential mechanism based on network pharmacology. J. Ethnopharmacol., 2020, 259, 112929.
[http://dx.doi.org/10.1016/j.jep.2020.112929] [PMID: 32416245]
[20]
Sharma, V.R.; Gupta, G.K.; Sharma, A.K.; Batra, N.; Sharma, D.K.; Joshi, A.; Sharma, A.K. PI3K/Akt/mTOR Intracellular Pathway and Breast Cancer: Factors, Mechanism and Regulation. Curr. Pharm. Des., 2017, 23(11), 1633-1638.
[http://dx.doi.org/10.2174/1381612823666161116125218] [PMID: 27848885]
[21]
Hua, H.; Kong, Q.; Zhang, H.; Wang, J.; Luo, T.; Jiang, Y. Targeting mTOR for cancer therapy. J. Hematol. Oncol., 2019, 12(1), 71.
[http://dx.doi.org/10.1186/s13045-019-0754-1] [PMID: 31277692]
[22]
Song, M.; Bode, A.M.; Dong, Z.; Lee, M.H. AKT as a Therapeutic Target for Cancer. Cancer Res., 2019, 79(6), 1019-1031.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-2738] [PMID: 30808672]
[23]
Matthews, J.M.; Lester, K.; Joseph, S.; Curtis, D.J. LIM-domain-only proteins in cancer. Nat. Rev. Cancer, 2013, 13(2), 111-122.
[http://dx.doi.org/10.1038/nrc3418] [PMID: 23303138]
[24]
Gerby, B.; Tremblay, C.S.; Tremblay, M.; Rojas-Sutterlin, S.; Herblot, S.; Hébert, J.; Sauvageau, G.; Lemieux, S.; Lécuyer, E.; Veiga, D.F.T.; Hoang, T. SCL, LMO1 and Notch1 reprogram thymocytes into self-renewing cells. PLoS Genet., 2014, 10(12), e1004768.
[http://dx.doi.org/10.1371/journal.pgen.1004768] [PMID: 25522233]
[25]
Zhu, S.; Zhang, X.; Weichert-Leahey, N.; Dong, Z.; Zhang, C.; Lopez, G.; Tao, T.; He, S.; Wood, A.C.; Oldridge, D.; Ung, C.Y.; van Ree, J.H.; Khan, A.; Salazar, B.M.; Lummertz da Rocha, E.; Zimmerman, M.W.; Guo, F.; Cao, H.; Hou, X.; Weroha, S.J.; Perez-Atayde, A.R.; Neuberg, D.S.; Meves, A.; McNiven, M.A.; van Deursen, J.M.; Li, H.; Maris, J.M.; Look, A.T. LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis. Cancer Cell, 2017, 32(3), 310-323.e5.
[http://dx.doi.org/10.1016/j.ccell.2017.08.002] [PMID: 28867147]
[26]
Du, L.; Zhao, Z.; Suraokar, M.; Shelton, S.S.; Ma, X.; Hsiao, T.H.; Minna, J.D.; Wistuba, I.; Pertsemlidis, A. LMO1 functions as an oncogene by regulating TTK expression and correlates with neuroendocrine differentiation of lung cancer. Oncotarget, 2018, 9(51), 29601-29618.
[http://dx.doi.org/10.18632/oncotarget.25642] [PMID: 30038707]
[27]
Wang, K.; Diskin, S.J.; Zhang, H.; Attiyeh, E.F.; Winter, C.; Hou, C.; Schnepp, R.W.; Diamond, M.; Bosse, K.; Mayes, P.A.; Glessner, J.; Kim, C.; Frackelton, E.; Garris, M.; Wang, Q.; Glaberson, W.; Chiavacci, R. Le Nguyen; Jagannathan, J.; Saeki, N.; Sasaki, H.; Grant, S.F.A.; Iolascon, A.; Mosse, Y.P.; Cole, K.A.; Li, H.; Devoto, M.; McGrady, P.W.; London, W.B.; Capasso, M.; Rahman, N.; Hakonarson, H.; Maris, J.M. Integrative genomics identifies LMO1 as a neuroblastoma oncogene. Nature, 2011, 469(7329), 216-220.
[http://dx.doi.org/10.1038/nature09609] [PMID: 21124317]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy