Isobavachalcone induces the apoptosis of gastric cancer cells via inhibition of the Akt and Erk pathways

Jin,Xiaohong; Shi,Yi

doi:10.3892/etm.2015.2904

Isobavachalcone induces the apoptosis of gastric cancer cells via inhibition of the Akt and Erk pathways

Authors:
- Xiaohong Jin
- Yi Shi
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Affiliations: Department of Oncology, Yunyang People's Hospital of Danyang, Danyang, Jiangsu 212300, P.R. China, Department of Stomatology, Danyang People's Hospital of Jiangsu, Danyang, Jiangsu 212300, P.R. China
Published online on: December 1, 2015 https://doi.org/10.3892/etm.2015.2904
Pages: 403-408
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In the present study, the MGC803 gastric cancer cell line was used as an experimental model to evaluate the potential role of isobavachalcone (IBC) in cell apoptosis, migration and invasion. The inhibitory effects of IBC on cell proliferation were determined using a methylthiazolyltetrazolium assay. Cellular morphological changes were assessed using Wright‑Giemsa staining, and cell apoptosis was evaluated by flow cytometric analysis. The results of the present study demonstrated that IBC inhibited the proliferation of MGC803 cells in a concentration‑ and time‑dependent manner. Furthermore, the wound healing and Matrigel™ Transwell® invasion assays demonstrated that IBC decreased cell migration and invasion in a concentration‑dependent manner. Western blotting was used to determine the protein expression levels of caspase‑3, B‑cell lymphoma‑2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax), as well as the key protein kinases in the Akt and extracellular signal‑regulated kinase (Erk) signaling pathways. During the IBC‑induced apoptosis of MGC803 cells, transient activation of phosphorylated (p)‑Akt and p‑Erk inhibited the activation of Akt and Erk, upregulated Bax expression, downregulated Bcl‑2 expression and activated caspase‑3. These results suggest that IBC inhibited the growth of MGC803 gastric cancer cells by regulating the protein expression of caspase‑3, Bcl‑2 and Bax. In addition, inhibition of the Akt and Erk signaling pathways may be important mechanisms underlying the IBC‑induced apoptosis of gastric cancer cells.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Guggenheim DE and Shah MA: Gastric cancer epidemiology and risk factors. J Surg Oncol. 107:230–236. 2013. View Article : Google Scholar : PubMed/NCBI
3	Cervantes A, Roda D, Tarazona N, Roselló S and Pérez-Fidalgo JA: Current questions for the treatment of advanced gastric cancer. Cancer Treat Rev. 39:60–67. 2013. View Article : Google Scholar : PubMed/NCBI
4	Jing H, Zhou X, Dong X, Cao J, Zhu H, Lou J, Hu Y, He Q and Yang B: Abrogation of Akt signaling by Isobavachalcone contributes to its anti-proliferative effects towards human cancer cells. Cancer Lett. 294:167–177. 2010. View Article : Google Scholar : PubMed/NCBI
5	Akihisa T, Tokuda H, Hasegawa D, Ukiya M, Kimura Y, Enjo F, Suzuki T and Nishino H: Chalcones and other compounds from the exudates of Angelica keiskei and their cancer chemopreventive effects. J Nat Prod. 69:38–42. 2006. View Article : Google Scholar : PubMed/NCBI
6	Bhalla VX, Nayak UR and Dev S: Some new flavonoids from Psoralea corylifolia. Tetrahedron Lett. 20:2401–2406. 1968. View Article : Google Scholar
7	Szliszka E, Jaworska D, Ksek M, Czuba ZP and Król W: Targeting death receptor TRAIL-R2 by chalcones for TRAIL-induced apoptosis in cancer cells. Int J Mol Sci. 13:15343–15359. 2012. View Article : Google Scholar : PubMed/NCBI
8	Szliszka E, Czuba ZP, Mazur B, Sedek L, Paradysz A and Krol W: Chalcones enhance TRAIL-induced apoptosis in prostate cancer cells. Int J Mol Sci. 11:1–13. 2009. View Article : Google Scholar : PubMed/NCBI
9	Li W, Li S, Higai K, Sasaki T, Asada Y, Ohshima S and Koike K: Evaluation of licorice flavonoids as protein tyrosine phosphatase 1B inhibitors. Bioorg Med Chem Lett. 23:5836–5839. 2013. View Article : Google Scholar : PubMed/NCBI
10	Nishimura R, Tabata K, Arakawa M, Ito Y, Kimura Y, Akihisa T, Nagai H, Sakuma A, Kohno H and Suzuki T: Isobavachalcone, a chalcone constituent of Angelica keiskei, induces apoptosis in neuroblastoma. Biol Pharm Bull. 30:1878–1883. 2007. View Article : Google Scholar : PubMed/NCBI
11	Jin X, Zhu Z and Shi Y: Metastasis mechanism and gene/protein expression in gastric cancer with distant organs metastasis. Bull Cancer. 101:E1–E12. 2014.PubMed/NCBI
12	Khan KH, Blanco-Codesido M and Molife LR: Cancer therapeutics, Targeting the apoptotic pathway. Crit Rev Oncol Hematol. 90:6200–219. 2014. View Article : Google Scholar
13	Westin JR: Status of PI/3K/Akt/mTOR pathway inhibitors in lymphoma. Clin Lymphoma Myeloma Leuk. 14:335–342. 2014. View Article : Google Scholar : PubMed/NCBI
14	Koehler BC, Jäger D and Schulze-Bergkamen H: Targeting cell death signaling in colorectal cancer Current strategies and future perspectives. World J Gastroenterol. 20:1923–1934. 2014. View Article : Google Scholar : PubMed/NCBI
15	Aranda F, Vacchelli E, Eggermont A, Galon J, Fridman WH, Zitvogel L, Kroemer G and Galluzzi L: Trial Watch, Immunostimulatory monoclonal antibodies in cancer therapy. Oncoimmunology. 3:e272972014. View Article : Google Scholar : PubMed/NCBI
16	Park JW, Choi YJ, Suh SI, Baek WK, Suh MH, Jin IN, Min DS, Woo JH, Chang JS, Passaniti A, Lee YH and Kwon TK: Bcl-2 overexpression attenuates resveratrol-induced apoptosis in U937 cells by inhibition of caspase-3 activity. Carcinogenesis. 22:1633–1639. 2001. View Article : Google Scholar : PubMed/NCBI
17	Sharawat SK, Bakhshi R, Vishnubhatla S, Gupta R and Bakhshi S: BAX/BCL2 RMFI ratio predicts better induction response in pediatric patients with acute myeloid leukemia. Pediatr Blood Cancer. 60:E63–E66. 2013. View Article : Google Scholar : PubMed/NCBI
18	Sjöström J, Blomqvist C, von Boguslawski K, Bengtsson NO, Mjaaland I, Malmström P, Ostenstadt B, Wist E, Valvere V, Takayama S, Reed JC and Saksela E: The predictive value of bcl-2, bax, bcl-xL, bag-1, fas and fasL for chemotherapy response in advanced breast cancer. Clin Cancer Res. 8:811–816. 2002.PubMed/NCBI
19	Dent P: Crosstalk between ERK AKT and cell survival. Cancer Biol Ther. 15:245–246. 2014. View Article : Google Scholar : PubMed/NCBI
20	Briest F and Grabowski P: PI3K-AKT-mTOR-signaling and beyond: The complex network in gastroenteropancreatic neuroendocrine neoplasms. Theranostics. 4:336–365. 2014. View Article : Google Scholar : PubMed/NCBI
21	Polivka J: Jr andJ anku F: Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol Ther. 142:164–175. 2014. View Article : Google Scholar : PubMed/NCBI
22	McCubrey JA, Steelman LS, Kempf CR, Chappell WH, Abrams SL, Stivala F, Malaponte G, Nicoletti F, Libra M, Bäsecke J, et al: Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways. J Cell Physiol. 226:2762–2781. 2011. View Article : Google Scholar : PubMed/NCBI
23	Infante JR, Fecher LA, Falchook GS, Nallapareddy S, Gordon MS, Becerra C, DeMarini DJ, Cox DS, Xu Y, Morris SR, et al: Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: A phase 1 dose-escalation trial. Lancet Oncol. 13:773–781. 2012. View Article : Google Scholar : PubMed/NCBI