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Article

Rottlerin inhibits cell growth, induces apoptosis and cell cycle arrest, and inhibits cell invasion in human hepatocellular carcinoma

  • Authors:
    • Jichan Shi
    • Hongye Ning
    • Guiqing He
    • Yitong Huang
    • Zhengxing Wu
    • Lingling Jin
    • Xiangao Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Infectious Disease, Wenzhou Central Hospital, Wenzhou, Zhejiang 325000, P.R. China, Department of Gynecologic Oncology, Wenzhou Central Hospital, Wenzhou, Zhejiang 325000, P.R. China
  • Pages: 459-464
    |
    Published online on: October 27, 2017
       https://doi.org/10.3892/mmr.2017.7924
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Abstract

Rottlerin, a polyphenolic compound, has been demonstrated to exhibit antitumor activity in various types of human cancer. Several studies have revealed that rottlerin exerts its anticancer function through PKC‑dependent and independent pathways. The transcriptional co‑activator with PDZ‑binding motif (TAZ) oncopreotein is an important molecule in regulation of the Hippo pathway in human cancer. The present study investigated whether rottlerin has a tumor suppressive role via inhibiting the expression of TAZ, using cell viability assay, apoptosis and cell cycle analyses, western blot analysis and Tanswell invasion assay. The results demonstrated that rottlerin suppressed cell growth, triggered cell apoptosis and induced cell cycle arrest. In addition, rottlerin inhibited cell migration and invasion in hepatocellular carcinoma (HCC) cells. Mechanistically, the results demonstrated that rottlerin exerted its antitumor activity partly through the inhibition of TAZ. In addition, the depletion of TAZ led to inhibited cell growth and invasion, whereas the overexpression of TAZ enhanced cell growth and invasion in the HCC cells. Taken together, these findings indicated that the inhibition of TAZ by rottlerin may be a novel strategy for treating HCC.
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1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Kudo M, Trevisani F, Abou-Alfa GK and Rimassa L: Hepatocellular carcinoma: Therapeutic guidelines and medical treatment. Liver Cancer. 6:16–26. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Maioli E, Torricelli C and Valacchi G: Rottlerin and cancer: Novel evidence and mechanisms. Scientific World Journal. 2012:3508262012. View Article : Google Scholar : PubMed/NCBI

5 

Gschwendt M, Müller HJ, Kielbassa K, Zang R, Kittstein W, Rincke G and Marks F: Rottlerin, a novel protein kinase inhibitor. Biochem Biophys Res Commun. 199:93–98. 1994. View Article : Google Scholar : PubMed/NCBI

6 

Parmer TG, Ward MD and Hait WN: Effects of rottlerin, an inhibitor of calmodulin-dependent protein kinase III, on cellular proliferation, viability, and cell cycle distribution in malignant glioma cells. Cell Growth Differ. 8:327–334. 1997.PubMed/NCBI

7 

Ni H, Ergin M, Tibudan SS, Denning MF, Izban KF and Alkan S: Protein kinase C-delta is commonly expressed in multiple myeloma cells and its downregulation by rottlerin causes apoptosis. Br J Haematol. 121:849–856. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Tillman DM, Izeradjene K, Szucs KS, Douglas L and Houghton JA: Rottlerin sensitizes colon carcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis via uncoupling of the mitochondria independent of protein kinase C. Cancer Res. 63:5118–5125. 2003.PubMed/NCBI

9 

Kim EH, Kim SU and Choi KS: Rottlerin sensitizes glioma cells to TRAIL-induced apoptosis by inhibition of Cdc2 and the subsequent downregulation of survivin and XIAP. Oncogene. 24:838–849. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Torricelli C, Fortino V, Capurro E, Valacchi G, Pacini A, Muscettola M, Soucek K and Maioli E: Rottlerin inhibits the nuclear factor kappaB/cyclin-D1 cascade in MCF-7 breast cancer cells. Life Sci. 82:638–643. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Basu A, Adkins B and Basu C: Down-regulation of caspase-2 by rottlerin via protein kinase C-delta-independent pathway. Cancer Res. 68:2795–2802. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Song KS, Kim JS, Yun EJ, Kim YR, Seo KS, Park JH, Jung YJ, Park JI, Kweon GR, Yoon WH, et al: Rottlerin induces autophagy and apoptotic cell death through a PKC-delta-independent pathway in HT1080 human fibrosarcoma cells: The protective role of autophagy in apoptosis. Autophagy. 4:650–658. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Barron DA and Kagey JD: The role of the Hippo pathway in human disease and tumorigenesis. Clin Transl Med. 3:252014. View Article : Google Scholar : PubMed/NCBI

14 

Feng J, Ren P, Gou J and Li Z: Prognostic significance of TAZ expression in various cancers: A meta-analysis. Onco Targets Ther. 9:5235–5244. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Zhang Y, Xue C, Cui H and Huang Z: High expression of TAZ indicates a poor prognosis in retinoblastoma. Diagn Pathol. 10:1872015. View Article : Google Scholar : PubMed/NCBI

16 

Zanconato F, Battilana G, Cordenonsi M and Piccolo S: YAP/TAZ as therapeutic targets in cancer. Curr Opin Pharmacol. 29:26–33. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Su J, Wang L, Yin X, Zhao Z, Hou Y, Ye X, Zhou X and Wang Z: Rottlerin exhibits anti-cancer effect through inactivation of S phase kinase-associated protein 2 in pancreatic cancer cells. Am J Cancer Res. 6:2178–2191. 2016.PubMed/NCBI

18 

Yin X, Zhang Y, Su J, Hou Y, Wang L, Ye X, Zhao Z, Zhou X, Li Y and Wang Z: Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells. Oncotarget. 7:66512–66524. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Zanconato F, Cordenonsi M and Piccolo S: YAP/TAZ at the roots of cancer. Cancer Cell. 29:783–803. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Lu W, Lin C and Li Y: Rottlerin induces Wnt co-receptor LRP6 degradation and suppresses both Wnt/β-catenin and mTORC1 signaling in prostate and breast cancer cells. Cell Signal. 26:1303–1309. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Kumar D, Shankar S and Srivastava RK: Rottlerin induces autophagy and apoptosis in prostate cancer stem cells via PI3K/Akt/mTOR signaling pathway. Cancer Lett. 343:179–189. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Singh BN, Kumar D, Shankar S and Srivastava RK: Rottlerin induces autophagy which leads to apoptotic cell death through inhibition of PI3K/Akt/mTOR pathway in human pancreatic cancer stem cells. Biochem Pharmacol. 84:1154–1163. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Lim JH, Woo SM, Min KJ, Park EJ, Jang JH, Seo BR, Iqbal T, Lee TJ, Kim SH, Choi YH and Kwon TK: Rottlerin induces apoptosis of HT29 colon carcinoma cells through NAG-1 upregulation via an ERK and p38 MAPK-dependent and PKC δ-independent mechanism. Chem Biol Interact. 197:1–7. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Wang L, Ye X, Cai X, Su J, Ma R, Yin X, Zhou X, Li H and Wang Z: Curcumin suppresses cell growth and invasion and induces apoptosis by down-regulation of Skp2 pathway in glioma cells. Oncotarget. 6:18027–18037. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Wang S, Ma K, Chen L, Zhu H, Liang S, Liu M and Xu N: TAZ promotes cell growth and inhibits Celastrol-induced cell apoptosis. Biosci Rep. 36:pii: e00386. 2016. View Article : Google Scholar

26 

Chen G, Xie J, Huang P and Yang Z: Overexpression of TAZ promotes cell proliferation, migration and epithelial-mesenchymal transition in ovarian cancer. Oncol Lett. 12:1821–1825. 2016.PubMed/NCBI

27 

Xie D, Cui J, Xia T, Jia Z, Wang L, Wei W, Zhu A, Gao Y, Xie K and Quan M: Hippo transducer TAZ promotes epithelial mesenchymal transition and supports pancreatic cancer progression. Oncotarget. 6:35949–35963. 2015.PubMed/NCBI

28 

Guo L, Zheng J, Zhang J, Wang H, Shao G and Teng L: Knockdown of TAZ modifies triple-negative breast cancer cell sensitivity to EGFR inhibitors by regulating YAP expression. Oncol Rep. 36:729–736. 2016. View Article : Google Scholar : PubMed/NCBI

29 

Gruber R, Panayiotou R, Nye E, Spencer-Dene B, Stamp G and Behrens A: YAP1 and TAZ control pancreatic cancer initiation in mice by direct up-regulation of JAK-STAT3 signaling. Gastroenterology. 151:526–539. 2016. View Article : Google Scholar : PubMed/NCBI

30 

Higashi T, Hayashi H, Kitano Y, Yamamura K, Kaida T, Arima K, Taki K, Nakagawa S, Okabe H, Nitta H, et al: Statin attenuates cell proliferative ability via TAZ (WWTR1) in hepatocellular carcinoma. Med Oncol. 33:1232016. View Article : Google Scholar : PubMed/NCBI

31 

Zhou X, Su J, Feng S, Wang L, Yin X, Yan J and Wang Z: Antitumor activity of curcumin is involved in down-regulation of YAP/TAZ expression in pancreatic cancer cells. Oncotarget. 7:79076–79088. 2016.PubMed/NCBI

32 

Gao Y, Shi Q, Xu S, Du C, Liang L, Wu K, Wang K, Wang X, Chang LS, He D and Guo P: Curcumin promotes KLF5 proteasome degradation through downregulating YAP/TAZ in bladder cancer cells. Int J Mol Sci. 15:15173–15187. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Oku Y, Nishiya N, Shito T, Yamamoto R, Yamamoto Y, Oyama C and Uehara Y: Small molecules inhibiting the nuclear localization of YAP/TAZ for chemotherapeutics and chemosensitizers against breast cancers. FEBS Open Bio. 5:542–549. 2015. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Shi J, Ning H, He G, Huang Y, Wu Z, Jin L and Jiang X: Rottlerin inhibits cell growth, induces apoptosis and cell cycle arrest, and inhibits cell invasion in human hepatocellular carcinoma. Mol Med Rep 17: 459-464, 2018.
APA
Shi, J., Ning, H., He, G., Huang, Y., Wu, Z., Jin, L., & Jiang, X. (2018). Rottlerin inhibits cell growth, induces apoptosis and cell cycle arrest, and inhibits cell invasion in human hepatocellular carcinoma. Molecular Medicine Reports, 17, 459-464. https://doi.org/10.3892/mmr.2017.7924
MLA
Shi, J., Ning, H., He, G., Huang, Y., Wu, Z., Jin, L., Jiang, X."Rottlerin inhibits cell growth, induces apoptosis and cell cycle arrest, and inhibits cell invasion in human hepatocellular carcinoma". Molecular Medicine Reports 17.1 (2018): 459-464.
Chicago
Shi, J., Ning, H., He, G., Huang, Y., Wu, Z., Jin, L., Jiang, X."Rottlerin inhibits cell growth, induces apoptosis and cell cycle arrest, and inhibits cell invasion in human hepatocellular carcinoma". Molecular Medicine Reports 17, no. 1 (2018): 459-464. https://doi.org/10.3892/mmr.2017.7924
Copy and paste a formatted citation
x
Spandidos Publications style
Shi J, Ning H, He G, Huang Y, Wu Z, Jin L and Jiang X: Rottlerin inhibits cell growth, induces apoptosis and cell cycle arrest, and inhibits cell invasion in human hepatocellular carcinoma. Mol Med Rep 17: 459-464, 2018.
APA
Shi, J., Ning, H., He, G., Huang, Y., Wu, Z., Jin, L., & Jiang, X. (2018). Rottlerin inhibits cell growth, induces apoptosis and cell cycle arrest, and inhibits cell invasion in human hepatocellular carcinoma. Molecular Medicine Reports, 17, 459-464. https://doi.org/10.3892/mmr.2017.7924
MLA
Shi, J., Ning, H., He, G., Huang, Y., Wu, Z., Jin, L., Jiang, X."Rottlerin inhibits cell growth, induces apoptosis and cell cycle arrest, and inhibits cell invasion in human hepatocellular carcinoma". Molecular Medicine Reports 17.1 (2018): 459-464.
Chicago
Shi, J., Ning, H., He, G., Huang, Y., Wu, Z., Jin, L., Jiang, X."Rottlerin inhibits cell growth, induces apoptosis and cell cycle arrest, and inhibits cell invasion in human hepatocellular carcinoma". Molecular Medicine Reports 17, no. 1 (2018): 459-464. https://doi.org/10.3892/mmr.2017.7924
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