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Article

Chloroform fraction of Scutellaria barbata D. Don inhibits the growth of colorectal cancer cells by activating miR‑34a

  • Authors:
    • Ling Zhang
    • Yi Fang
    • Jian-Yu Feng
    • Qiao-Yan Cai
    • Li-Hui Wei
    • Shan Lin
    • Jun Peng
  • View Affiliations / Copyright

    Affiliations: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
  • Pages: 3695-3701
    |
    Published online on: May 4, 2017
       https://doi.org/10.3892/or.2017.5625
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Abstract

Scutellaria barbata D. Don (SB) is a well known formula in traditional Chinese medicine, which exhibits potent anticancer effects on various cancers. Many miRNAs play crucial roles in the regulation of cancer, for instance, miR‑34a functions as a tumor suppressor, and is often downregulated during cancer. In this study, we investigated the role of ECSB in suppressing the growth of human colon cancer HCT‑8 cells, and whether this is mediated by regulation of miR‑34a and its downstream target genes, using real-time PCR and western blot analysis. ECSB treatment significantly inhibited the proliferation of HCT‑8 cells and promoted apoptosis in a dose-dependent manner. In addition, ECSB treatment significantly increased the level of miR‑34a expression and decreased the levels of Bcl-2, Notch1/2 and Jagged1 expression. Furthermore, knockdown of miR‑34a expression through transfection of anti-miR‑34a oligonucleotide was significantly reversed by ECSB treatment. Likewise, knockdown of miR‑34a resulted in significant upregulation of Bcl-2, Notch1/2 and Jagged1 expression, which was reversed following ECSB treatment. Therefore, this study reveals that ECSB inhibited cancer cell growth via promoting apoptosis and inhibiting proliferation, through regulation of miR‑34a. These findings further support the use of ECSB as an effective therapeutic agent against colon cancer.
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1 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Cekaite L, Eide PW, Lind GE, Skotheim RI and Lothe RA: MicroRNAs as growth regulators, their function and biomarker status in colorectal cancer. Oncotarget. 7:6476–6505. 2016.PubMed/NCBI

3 

Siegel R, Desantis C and Jemal A: Colorectal cancer statistics, 2014. CA Cancer J Clin. 64:104–117. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Yang J, Yang G, Hou G, Liu Q, Hu W, Zhao PU and He YI: Scutellaria barbata D. Don polysaccharides inhibit the growth of Calu-3 xenograft tumors via suppression of the HER2 pathway and angiogenesis. Oncol Lett. 9:2721–2725. 2015.PubMed/NCBI

5 

Kim KW, Jin UH, Kim DI, Lee TK, Kim MS, Oh MJ, Kim MS, Kwon DY, Lee YC and Kim CH: Antiproliferative effect of Scutellaria barbata D. Don. on cultured human uterine leiomyoma cells by down-regulation of the expression of Bcl-2 protein. Phytother Res. 22:583–590. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Gao J, Lu WF, Dai ZJ, Lin S, Zhao Y, Li S, Zhao NN, Wang XJ, Kang HF, Ma XB, et al: Induction of apoptosis by total flavonoids from Scutellaria barbata D. Don in human hepatocarcinoma MHCC97-H cells via the mitochondrial pathway. Tumour Biol. 35:2549–2559. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Lin J, Chen Y, Cai Q, Wei L, Zhan Y, Shen A, Sferra TJ and Peng J: Scutellaria Barbata D Don Inhibits Colorectal Cancer Growth via Suppression of Multiple Signaling Pathways. Integr Cancer Ther. 13:240–248. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Wei L, Lin J, Wu G, Xu W, Li H, Hong Z and Peng J: Scutellaria barbata D. Don induces G1/S arrest via modulation of p53 and Akt pathways in human colon carcinoma cells. Oncol Rep. 29:1623–1628. 2013.PubMed/NCBI

9 

Wei L, Lin J, Xu W, Cai Q, Shen A, Hong Z and Peng J: Scutellaria barbata D. Don inhibits tumor angiogenesis via suppression of Hedgehog pathway in a mouse model of colorectal cancer. Int J Mol Sci. 13:9419–9430. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Jiang Q, Li Q, Chen H, Shen A, Cai Q, Lin J and Peng J: Scutellaria barbata D. Don inhibits growth and induces apoptosis by suppressing IL-6-inducible STAT3 pathway activation in human colorectal cancer cells. Exp Ther Med. 10:1602–1608. 2015.PubMed/NCBI

11 

Zhang L, Cai Q, Lin J, Fang Y, Zhan Y, Shen A, Wei L, Wang L and Peng J: Chloroform fraction of Scutellaria barbata D. Don promotes apoptosis and suppresses proliferation in human colon cancer cells. Mol Med Rep. 9:701–706. 2014.PubMed/NCBI

12 

Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, et al: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 101:pp. 2999–3004. 2004; View Article : Google Scholar : PubMed/NCBI

16 

Li Y, Guessous F, Zhang Y, Dipierro C, Kefas B, Johnson E, Marcinkiewicz L, Jiang J, Yang Y, Schmittgen TD, et al: MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res. 69:7569–7576. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Hermeking H: The miR-34 family in cancer and apoptosis. Cell Death Differ. 17:193–199. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Yamakuchi M, Ferlito M and Lowenstein CJ: miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci USA. 105:pp. 13421–13426. 2008; View Article : Google Scholar : PubMed/NCBI

19 

Tazawa H, Tsuchiya N, Izumiya M and Nakagama H: Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci USA. 104:pp. 15472–15477. 2007; View Article : Google Scholar : PubMed/NCBI

20 

Ma Y, Bao-Han W, Lv X, Su Y, Zhao X, Yin Y, Zhang X, Zhou Z, MacNaughton WK and Wang H: MicroRNA-34a mediates the autocrine signaling of PAR2-activating proteinase and its role in colonic cancer cell proliferation. PLoS One. 8:e723832013. View Article : Google Scholar : PubMed/NCBI

21 

Wu J, Wu G, Lv L, Ren YF, Zhang XJ, Xue YF, Li G, Lu X, Sun Z and Tang KF: MicroRNA-34a inhibits migration and invasion of colon cancer cells via targeting to Fra-1. Carcinogenesis. 33:519–528. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Bu P, Chen KY, Chen JH, Wang L, Walters J, Shin YJ, Goerger JP, Sun J, Witherspoon M, Rakhilin N, et al: A microRNA miR-34a-regulated bimodal switch targets Notch in colon cancer stem cells. Cell Stem Cell. 12:602–615. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Chi Y and Zhou D: MicroRNAs in colorectal carcinoma - from pathogenesis to therapy. J Exp Clin Cancer Res. 35:432016. View Article : Google Scholar : PubMed/NCBI

24 

Buriani A, Garcia-Bermejo ML, Bosisio E, Xu Q, Li H, Dong X, Simmonds MS, Carrara M, Tejedor N, Lucio-Cazana J, et al: Omic techniques in systems biology approaches to traditional Chinese medicine research: Present and future. J Ethnopharmacol. 140:535–544. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Shen A, Lin W, Chen Y, Liu L, Chen H, Zhuang Q, Lin J, Sferra TJ and Peng J: Pien Tze Huang inhibits metastasis of human colorectal carcinoma cells via modulation of TGF-β1/ZEB/miR-200 signaling network. Int J Oncol. 46:685–690. 2015.PubMed/NCBI

26 

Pan L, Sheung Y, Guo W, Rong ZB and Cai ZM: 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. 2016:91749032016. View Article : Google Scholar : PubMed/NCBI

27 

Guo H, Lu Y, Wang J, Liu X, Keller ET, Liu Q, Zhou Q and Zhang J: Targeting the Notch signaling pathway in cancer therapeutics. Thorac Cancer. 5:473–486. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Boareto M, Jolly MK, Goldman A, Pietilä M, Mani SA, Sengupta S, Ben-Jacob E, Levine H and Onuchic JN: Notch-Jagged signalling can give rise to clusters of cells exhibiting a hybrid epithelial/mesenchymal phenotype. J R Soc Interface. 13:132016. View Article : Google Scholar

29 

Pang RTK, Leung CON, Ye TM, Liu W, Chiu PC, Lam KK, Lee KF and Yeung WS: MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. Carcinogenesis. 31:1037–1044. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Ye QF, Zhang YC, Peng XQ, Long Z, Ming YZ and He LY: Silencing Notch-1 induces apoptosis and increases the chemosensitivity of prostate cancer cells to docetaxel through Bcl-2 and Bax. Oncol Lett. 3:879–884. 2012.PubMed/NCBI

31 

Gao F, Yao M, Shi Y, Hao J, Ren Y, Liu Q, Wang X and Duan H: Notch pathway is involved in high glucose-induced apoptosis in podocytes via Bcl-2 and p53 pathways. J Cell Biochem. 114:1029–1038. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Zhang C, Mo R, Yin B, Zhou L, Liu Y and Fan J: Tumor suppressor microRNA-34a inhibits cell proliferation by targeting Notch1 in renal cell carcinoma. Oncol Lett. 7:1689–1694. 2014.PubMed/NCBI

33 

Xia J, Duan Q, Ahmad A, Bao B, Banerjee S, Shi Y, Ma J, Geng J, Chen Z, Rahman KM, et al: Genistein inhibits cell growth and induces apoptosis through up-regulation of miR-34a in pancreatic cancer cells. Curr Drug Targets. 13:1750–1756. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Jia H, Yang Q, Wang T, Cao Y, Jiang QY, Ma HD, Sun HW, Hou MX, Yang YP and Feng F: Rhamnetin induces sensitization of hepatocellular carcinoma cells to a small molecular kinase inhibitor or chemotherapeutic agents. Biochim Biophys Acta. 1860:1417–1430. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N, Bentwich Z and Oren M: Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell. 26:731–743. 2007. View Article : Google Scholar : PubMed/NCBI

36 

Lodygin D, Tarasov V, Epanchintsev A, Berking C, Knyazeva T, Körner H, Knyazev P, Diebold J and Hermeking H: Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle. 7:2591–2600. 2008. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhang L, Fang Y, Feng J, Cai Q, Wei L, Lin S and Peng J: Chloroform fraction of Scutellaria barbata D. Don inhibits the growth of colorectal cancer cells by activating miR‑34a. Oncol Rep 37: 3695-3701, 2017.
APA
Zhang, L., Fang, Y., Feng, J., Cai, Q., Wei, L., Lin, S., & Peng, J. (2017). Chloroform fraction of Scutellaria barbata D. Don inhibits the growth of colorectal cancer cells by activating miR‑34a. Oncology Reports, 37, 3695-3701. https://doi.org/10.3892/or.2017.5625
MLA
Zhang, L., Fang, Y., Feng, J., Cai, Q., Wei, L., Lin, S., Peng, J."Chloroform fraction of Scutellaria barbata D. Don inhibits the growth of colorectal cancer cells by activating miR‑34a". Oncology Reports 37.6 (2017): 3695-3701.
Chicago
Zhang, L., Fang, Y., Feng, J., Cai, Q., Wei, L., Lin, S., Peng, J."Chloroform fraction of Scutellaria barbata D. Don inhibits the growth of colorectal cancer cells by activating miR‑34a". Oncology Reports 37, no. 6 (2017): 3695-3701. https://doi.org/10.3892/or.2017.5625
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang L, Fang Y, Feng J, Cai Q, Wei L, Lin S and Peng J: Chloroform fraction of Scutellaria barbata D. Don inhibits the growth of colorectal cancer cells by activating miR‑34a. Oncol Rep 37: 3695-3701, 2017.
APA
Zhang, L., Fang, Y., Feng, J., Cai, Q., Wei, L., Lin, S., & Peng, J. (2017). Chloroform fraction of Scutellaria barbata D. Don inhibits the growth of colorectal cancer cells by activating miR‑34a. Oncology Reports, 37, 3695-3701. https://doi.org/10.3892/or.2017.5625
MLA
Zhang, L., Fang, Y., Feng, J., Cai, Q., Wei, L., Lin, S., Peng, J."Chloroform fraction of Scutellaria barbata D. Don inhibits the growth of colorectal cancer cells by activating miR‑34a". Oncology Reports 37.6 (2017): 3695-3701.
Chicago
Zhang, L., Fang, Y., Feng, J., Cai, Q., Wei, L., Lin, S., Peng, J."Chloroform fraction of Scutellaria barbata D. Don inhibits the growth of colorectal cancer cells by activating miR‑34a". Oncology Reports 37, no. 6 (2017): 3695-3701. https://doi.org/10.3892/or.2017.5625
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