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Article

Maslinic acid suppresses the growth of human gastric cells by inducing apoptosis via inhibition of the interleukin-6 mediated Janus kinase/signal transducer and activator of transcription 3 signaling pathway

  • Authors:
    • Deyou Wang
    • Sifeng Tang
    • Qiwen Zhang
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, Laiwu People's Hospital, Laiwu, Shandong 271100, P.R. China
  • Pages: 4875-4881
    |
    Published online on: April 21, 2017
       https://doi.org/10.3892/ol.2017.6073
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Abstract

The present study aimed to determine whether maslinic acid effectively inhibits the proliferation of MKN28 cells, and to investigate the mechanisms underlying its antitumor functions. MKN28 cell viability was evaluated using a Cell Counting Kit-8, cell proliferation was analyzed by a colony formation assay and flow cytometry was used to investigate the rate of apoptosis. Western blot analysis was performed in order to determine the differential expression levels of Janus kinase (JAK), signal transducer and activator of transcription 3 (STAT3) and apoptosis associated proteins B‑cell lymphoma 2 (Bcl‑2), Bcl‑2 associated X protein (Bax) and Bcl‑2 associated agonist of cell death (Bad). Interleukin‑6 (IL‑6) concentration was evaluated using ELISA. IL‑6 and anti‑IL‑6 antibodies were used to investigate the role of IL‑6 in MKN28 cells treated with maslinic acid proliferation, and the STAT3 phosphorylation rates. The results demonstrated that maslinic acid treatment significantly reduced cell proliferation, induced apoptosis and was accompanied by a significant decrease in Bcl‑2, Bax and Bad expression levels. Maslinic acid treatment also resulted in the downregulation of phosphorylated‑STAT3 and JAK2, and significantly inhibited the protein expression of IL‑6. Maslinic acid is able to inhibit MKN28 cell proliferation and the phosphorylation of STAT3 by downregulating the expression of IL‑6. These results suggest that maslinic acid suppresses the growth of MKN28 cells by inducing apoptosis via its inhibition of the IL‑6/JAK/STAT3 signaling cascade.
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1 

Reyes-Zurita FJ, Rufino-Palomares EE, Lupiáñez JA and Cascante M: Maslinic acid, a natural triterpene from Olea europaea L., induces apoptosis in HT29 human colon-cancer cells via the mitochondrial apoptotic pathway. Cancer Lett. 273:44–54. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Pavel IZ, Danciu C, Oprean C, Dehelean CA, Muntean D, Csuk R and Muntean DM: In vitro evaluation of the antimicrobial ability and cytotoxicity on two melanoma cell lines of a benzylamide derivative of maslinic acid. Anal Cell Pathol (Amst). 2016:27876232016.PubMed/NCBI

3 

Parra A, Rivas F, Lopez PE, Garcia-Granados A, Martinez A, Albericio F, Marquez N and Muñoz E: Solution- and solid-phase synthesis and anti-HIV activity of maslinic acid derivatives containing amino acids and peptides. Bioorg Med Chem. 17:1139–1145. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Nieto FR, Cobos EJ, Entrena JM, Parra A, García-Granados A and Baeyens JM: Antiallodynic and analgesic effects of maslinic acid, a pentacyclic triterpenoid from Olea europaea. J Nat Prod. 76:737–740. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Zhang S, Ding D, Zhang X, Shan L and Liu Z: Maslinic acid induced apoptosis in bladder cancer cells through activating p38 MAPK signaling pathway. Mol Cell Biochem. 392:281–287. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Park SY, Nho CW, Kwon DY, Kang YH, Lee KW and Park JH: Maslinic acid inhibits the metastatic capacity of DU145 human prostate cancer cells: Possible mediation via hypoxia-inducible factor-1α signalling. Br J Nutr. 109:210–222. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Rufino-Palomares EE, Reyes-Zurita FJ, García-Salguero L, Mokhtari K, Medina PP, Lupiáñez JA and Peragón J: Maslinic acid, a triterpenic anti-tumoural agent, interferes with cytoskeleton protein expression in HT29 human colon-cancer cells. J Proteomics. 83:15–25. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Reyes-Zurita FJ, Pachón-Peña G, Lizárraga D, Rufino-Palomares EE, Cascante M and Lupiáñez JA: The natural triterpene maslinic acid induces apoptosis in HT29 colon cancer cells by a JNK-p53-dependent mechanism. BMC Cancer. 11:1542011. View Article : Google Scholar : PubMed/NCBI

9 

Burger R: Impact of interleukin-6 in hematological malignancies. Transfus Med Hemother. 40:336–343. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Reynaud D, Pietras E, Barry-Holson K, Mir A, Binnewies M, Jeanne M, Sala-Torra O, Radich JP and Passegué E: IL-6 controls leukemic multipotent progenitor cell fate and contributes to chronic myelogenous leukemia development. Cancer Cell. 20:661–673. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Hirano T, Ishihara K and Hibi M: Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene. 19:2548–2556. 2000. View Article : Google Scholar : PubMed/NCBI

12 

Heinrich P, Behrmann I, Müller-Newen G, Schaper F and Graeve L: Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J. 334:297–314. 1998. View Article : Google Scholar : PubMed/NCBI

13 

Ogata A, Chauhan D, Teoh G, Treon SP, Urashima M, Schlossman RL and Anderson KC: IL-6 triggers cell growth via the Ras-dependent mitogen-activated protein kinase cascade. J Immunol. 159:2212–2221. 1997.PubMed/NCBI

14 

Huang W, Yu LF, Zhong J, Wu W, Zhu JY, Jiang FX and Wu YL: Stat3 is involved in angiotensin II-induced expression of MMP2 in gastric cancer cells. Dig Dis Sci. 54:2056–2062. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Ding SZ, Cho CH and Lam SK: Regulation of interleukin 6 production in a human gastric epithelial cell line MKN-28. Cytokine. 12:1129–1135. 2000. View Article : Google Scholar : PubMed/NCBI

16 

To KF, Chan MW, Leung WK, Ng EK, Yu J, Bai AH, Lo AW, Chu SH, Tong JH, Lo KW, et al: Constitutional activation of IL-6-mediated JAK/STAT pathway through hypermethylation of SOCS-1 in human gastric cancer cell line. Br J Cancer. 91:1335–1341. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Strober W: Trypan blue exclusion test of cell viability. Curr Protoc Immunol Appendix. 3:Appendix 3B. 2001. View Article : Google Scholar

18 

Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R, Ciliberto G, Moscinski L, Fernández-Luna JL, Nuñez G, et al: Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity. 10:105–115. 1999. View Article : Google Scholar : PubMed/NCBI

19 

Shain KH, Yarde DN, Meads MB, Huang M, Jove R, Hazlehurst LA and Dalton WS: Beta1 integrin adhesion enhances IL-6-mediated STAT3 signaling in myeloma cells: Implications for microenvironment influence on tumor survival and proliferation. Cancer Res. 69:1009–1015. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Zhong Z, Wen Z and Darnell JE Jr: Stat3: A STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science. 264:95–98. 1994. View Article : Google Scholar : PubMed/NCBI

21 

Al Zaid Siddiquee K and Turkson J: STAT3 as a target for inducing apoptosis in solid and hematological tumors. Cell Res. 18:254–267. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Li C, Yang Z, Zhai C, Qiu W, Li D, Yi Z, Wang L, Tang J, Qian M, Luo J and Liu M: Maslinic acid potentiates the anti-tumor activity of tumor necrosis factor alpha by inhibiting NF-kappaB signaling pathway. Mol Cancer. 9:732010. View Article : Google Scholar : PubMed/NCBI

23 

Wu DM, Zhao D, Li DZ, Xu DY, Chu WF and Wang XF: Maslinic acid induces apoptosis in salivary gland adenoid cystic carcinoma cells by Ca2+-evoked p38 signaling pathway. Naunyn Schmiedebergs Arch Pharmacol. 383:321–330. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Reyes-Zurita FJ, Rufino-Palomares EE, Lupiáñez JA and Cascante M: Maslinic acid, a natural triterpene from Olea europaea L., induces apoptosis in HT29 human colon-cancer cells via the mitochondrial apoptotic pathway. Cancer Lett. 273:44–54. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Hsum YW, Yew WT, Hong PL, Soo KK, Hoon LS, Chieng YC and Mooi LY: Cancer chemopreventive activity of maslinic acid: Suppression of COX-2 expression and inhibition of NF-κB and AP-1 activation in raji cells. Planta Med. 77:152–157. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Coussens LM and Werb Z: Inflammation and cancer. Nature. 420:860–867. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Hodge DR, Hurt EM and Farrar WL: The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer. 41:2502–2512. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K, Taga T and Kishimoto T: IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. Science. 260:1808–1810. 1993. View Article : Google Scholar : PubMed/NCBI

29 

Heinrich PC, Behrmann I, Müller-Newen G, Schaper F and Graeve L: Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J. 334:297–314. 1998. View Article : Google Scholar : PubMed/NCBI

30 

Kanda N, Seno H, Konda Y, Marusawa H, Kanai M, Nakajima T, Kawashima T, Nanakin A, Sawabu T, Uenoyama Y, et al: STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene. 23:4921–4929. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Endo TA, Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, et al: A new protein containing an SH2 domain that inhibits JAK kinases. Nature. 387:921–924. 1997. View Article : Google Scholar : PubMed/NCBI

32 

Yadav A, Kumar B, Datta J, Teknos TN and Kumar P: IL-6 promotes head and neck tumor metastasis by inducing epithelial-mesenchymal transition via the JAK-STAT3-SNAIL signaling pathway. Mol Cancer Res. 9:1658–1667. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Sriuranpong V, Park JI, Amornphimoltham P, Patel V, Nelkin BD and Gutkind JS: Epidermal growth factor receptor-independent constitutive activation of STAT3 in head and neck squamous cell carcinoma is mediated by the autocrine/paracrine stimulation of the interleukin 6/gp130 cytokine system. Cancer Res. 63:2948–2956. 2003.PubMed/NCBI

34 

Alas S and Bonavida B: Rituximab inactivates signal transducer and activation of transcription 3 (STAT3) activity in B-non-Hodgkin's lymphoma through inhibition of the interleukin 10 autocrine/paracrine loop and results in down-regulation of Bcl-2 and sensitization to cytotoxic drugs. Cancer Res. 61:5137–5144. 2001.PubMed/NCBI

35 

Sano M, Fukuda K, Kodama H, Takahashi T, Kato T, Hakuno D, Sato T, Manabe T, Tahara S and Ogawa S: Autocrine/Paracrine secretion of IL-6 family cytokines causes angiotensin II-induced delayed STAT3 activation. Biochem Biophys Res Commun. 269:798–802. 2000. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang D, Tang S and Zhang Q: Maslinic acid suppresses the growth of human gastric cells by inducing apoptosis via inhibition of the interleukin-6 mediated Janus kinase/signal transducer and activator of transcription 3 signaling pathway. Oncol Lett 13: 4875-4881, 2017.
APA
Wang, D., Tang, S., & Zhang, Q. (2017). Maslinic acid suppresses the growth of human gastric cells by inducing apoptosis via inhibition of the interleukin-6 mediated Janus kinase/signal transducer and activator of transcription 3 signaling pathway. Oncology Letters, 13, 4875-4881. https://doi.org/10.3892/ol.2017.6073
MLA
Wang, D., Tang, S., Zhang, Q."Maslinic acid suppresses the growth of human gastric cells by inducing apoptosis via inhibition of the interleukin-6 mediated Janus kinase/signal transducer and activator of transcription 3 signaling pathway". Oncology Letters 13.6 (2017): 4875-4881.
Chicago
Wang, D., Tang, S., Zhang, Q."Maslinic acid suppresses the growth of human gastric cells by inducing apoptosis via inhibition of the interleukin-6 mediated Janus kinase/signal transducer and activator of transcription 3 signaling pathway". Oncology Letters 13, no. 6 (2017): 4875-4881. https://doi.org/10.3892/ol.2017.6073
Copy and paste a formatted citation
x
Spandidos Publications style
Wang D, Tang S and Zhang Q: Maslinic acid suppresses the growth of human gastric cells by inducing apoptosis via inhibition of the interleukin-6 mediated Janus kinase/signal transducer and activator of transcription 3 signaling pathway. Oncol Lett 13: 4875-4881, 2017.
APA
Wang, D., Tang, S., & Zhang, Q. (2017). Maslinic acid suppresses the growth of human gastric cells by inducing apoptosis via inhibition of the interleukin-6 mediated Janus kinase/signal transducer and activator of transcription 3 signaling pathway. Oncology Letters, 13, 4875-4881. https://doi.org/10.3892/ol.2017.6073
MLA
Wang, D., Tang, S., Zhang, Q."Maslinic acid suppresses the growth of human gastric cells by inducing apoptosis via inhibition of the interleukin-6 mediated Janus kinase/signal transducer and activator of transcription 3 signaling pathway". Oncology Letters 13.6 (2017): 4875-4881.
Chicago
Wang, D., Tang, S., Zhang, Q."Maslinic acid suppresses the growth of human gastric cells by inducing apoptosis via inhibition of the interleukin-6 mediated Janus kinase/signal transducer and activator of transcription 3 signaling pathway". Oncology Letters 13, no. 6 (2017): 4875-4881. https://doi.org/10.3892/ol.2017.6073
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