Licochalcone A inhibits PI3K/Akt/mTOR signaling pathway activation and promotes autophagy in breast cancer cells

Xue,Lei; Zhang,Wei‑Jie; Fan,Qing‑Xia; Wang,Liu‑Xing

doi:10.3892/ol.2017.7451

Licochalcone A inhibits PI3K/Akt/mTOR signaling pathway activation and promotes autophagy in breast cancer cells

Authors:
- Lei Xue
- Wei‑Jie Zhang
- Qing‑Xia Fan
- Liu‑Xing Wang
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Affiliations: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: November 21, 2017 https://doi.org/10.3892/ol.2017.7451
Pages: 1869-1873

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Abstract

Previous studies have demonstrated that Licochalcone A possesses anti‑inflammatory, anticancer, anti‑bacterial, anti‑malarial and anti‑parasitic activities. In the present study the potential anticancer effects of Licochalcone A on MCF‑7 cells were investigated. Licochalcone A significantly decreased cell viability and promoted autophagy and apoptosis, as demonstrated by an MTT assay, acridine orange staining and Annexin V‑fluorescein isothiocyanate staining, respectively. Western blot analyses demonstrated that Licochalcone A treatment activated the LC3‑II signaling pathway while suppressing the phosphoinositide 3‑kinase (PI3K)/RAC‑α serine‑threonine‑protein kinase (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. In addition, Licochalcone A significantly increased caspase‑3 activity and significantly decreased B‑cell lymphoma‑2 expression. The results from the present study indicate that Licochalcone A inhibits PI3K/Akt/mTOR activation, and promotes autophagy and apoptosis in MCF‑7 cells.

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1	Bouvet V, Jans HS, Wuest M, Soueidan OM, Grant T, Mercer J, McEwan AJ, West FG, Cheeseman CI and Wuest F: Erratum: Automated synthesis and dosimetry of 6-deoxy-6-[F]fluoro-D-fructose (6-[F]FDF): A radiotracer for imaging of GLUT5 in breast cancer. Am J Nucl Med Mol Imaging. 5:952014.PubMed/NCBI
2	Zarzynska JM: The importance of autophagy regulation in breast cancer development and treatment. Biomed Res Int. 2014:7103452014. View Article : Google Scholar : PubMed/NCBI
3	Pu Z, Zhang X, Chen Q, Yuan X and Xie H: Establishment of an expression platform of OATP1B1 388GG and 521CC genetic polymorphism and the therapeutic effect of tamoxifen in MCF-7 cells. Oncol Rep. 33:2420–2428. 2015. View Article : Google Scholar : PubMed/NCBI
4	Wang LW, Qu AP, Yuan JP, Chen C, Sun SR, Hu MB, Liu J and Li Y: Computer-based image studies on tumor nests mathematical features of breast cancer and their clinical prognostic value. PLoS One. 8:e823142013. View Article : Google Scholar : PubMed/NCBI
5	Chukkapalli S, Amessou M, Dilly AK, Dekhil H, Zhao J, Liu Q, Bejna A, Thomas RD, Bandyopadhyay S, Bismar TA, et al: Role of the EphB2 receptor in autophagy, apoptosis and invasion in human breast cancer cells. Exp Cell Res. 320:233–246. 2014. View Article : Google Scholar : PubMed/NCBI
6	Fang WB, Yao M, Jokar I, Alhakamy N, Berkland C, Chen J, Brantley-Sieders D and Cheng N: The CCL2 chemokine is a negative regulator of autophagy and necrosis in luminal B breast cancer cells. Breast Cancer Res Treat. 150:309–320. 2015. View Article : Google Scholar : PubMed/NCBI
7	Lamparska-Przybysz M, Gajkowska B and Motyl T: BID-deficient breast cancer MCF-7 cells as a model for the study of autophagy in cancer therapy. Autophagy. 2:47–48. 2006. View Article : Google Scholar : PubMed/NCBI
8	Zhang H, Guo M, Chen JH, Wang Z, Du XF, Liu PX and Li WH: Osteopontin knockdown inhibits αv,β3 integrin-induced cell migration and invasion and promotes apoptosis of breast cancer cells by inducing autophagy and inactivating the PI3K/Akt/mTOR pathway. Cell Physiol Biochem. 33:991–1002. 2014. View Article : Google Scholar : PubMed/NCBI
9	Kim KH, Yoon G, Cho JJ, Cho JH, Cho YS, Chae JI and Shim JH: Licochalcone A induces apoptosis in malignant pleural mesothelioma through downregulation of Sp1 and subsequent activation of mitochondria-related apoptotic pathway. Int J Oncol. 46:1385–1392. 2015. View Article : Google Scholar : PubMed/NCBI
10	Chen M, Theander TG, Christensen SB, Hviid L, Zhai L and Kharazmi A: Licochalcone A, a new antimalarial agent, inhibits in vitro growth of the human malaria parasite Plasmodium falciparum and protects mice from P. yoelii infection. Antimicrob Agents Chemother. 38:1470–1475. 1994. View Article : Google Scholar : PubMed/NCBI
11	Shibata S, Inoue H, Iwata S, Ma RD, Yu LJ, Ueyama H, Takayasu J, Hasegawa T, Tokuda H, Nishino A, et al: Inhibitory effects of licochalcone A isolated from Glycyrrhiza inflata root on inflammatory ear edema and tumour promotion in mice. Planta Med. 57:221–224. 1991. View Article : Google Scholar : PubMed/NCBI
12	Rovito D, Giordano C, Plastina P, Barone I, De Amicis F, Mauro L, Rizza P, Lanzino M, Catalano S, Bonofiglio D and Andò S: Omega-3 DHA- and EPA-dopamine conjugates induce PPARgamma-dependent breast cancer cell death through autophagy and apoptosis. Biochim Biophys Acta. 1850:2185–2195. 2015. View Article : Google Scholar : PubMed/NCBI
13	Jain K, Paranandi KS, Sridharan S and Basu A: Autophagy in breast cancer and its implications for therapy. Am J Cancer Res. 3:251–265. 2013.PubMed/NCBI
14	Yang P, Tuo L, Wu Q and Cao X: Licochalcone-A sensitizes human esophageal carcinoma cells to TRAIL-mediated apoptosis by proteasomal degradation of XIAP. Hepatogastroenterology. 61:1229–1234. 2014.PubMed/NCBI
15	Huang HC, Tsai LL, Tsai JP, Hsieh SC, Yang SF, Hsueh JT and Hsieh YH: Licochalcone A inhibits the migration and invasion of human lung cancer cells via inactivation of the Akt signaling pathway with downregulation of MMP-1/−3 expression. Tumour Biol. 35:12139–12149. 2014. View Article : Google Scholar : PubMed/NCBI
16	Zeng G, Shen H, Yang Y, Cai X and Xun W: Licochalcone A as a potent antitumor agent suppresses growth of human oral cancer SCC-25 cells in vitro via caspase-3 dependent pathways. Tumour Biol. 35:6549–6555. 2014. View Article : Google Scholar : PubMed/NCBI
17	Chang L, Graham PH, Hao J, Ni J, Bucci J, Cozzi PJ, Kearsley JH and Li Y: PI3K/Akt/mTOR pathway inhibitors enhance radiosensitivity in radioresistant prostate cancer cells through inducing apoptosis, reducing autophagy, suppressing NHEJ and HR repair pathways. Cell Death Dis. 5:e14372014. View Article : Google Scholar : PubMed/NCBI
18	Tsai JP, Lee CH, Ying TH, Lin CL, Lin CL, Hsueh JT and Hsieh YH: Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells. Oncotarget. 6:28851–28866. 2015. View Article : Google Scholar : PubMed/NCBI
19	Hao W, Yuan X, Yu L, Gao C, Sun X, Wang D and Zheng Q: Licochalcone A-induced human gastric cancer BGC-823 cells apoptosis by regulating ROS-mediated MAPKs and PI3K/AKT signaling pathways. Sci Rep. 5:103362015. View Article : Google Scholar : PubMed/NCBI
20	Liu C, Xu P, Chen D, Fan X, Xu Y, Li M, Yang X and Wang C: Roles of autophagy-related genes Beclin-1 and LC3 in the development and progression of prostate cancer and benign prostatic hyperplasia. Biomed Rep. 1:855–860. 2013.PubMed/NCBI
21	Pan ST, Qin Y, Zhou ZW, He ZX, Zhang X, Yang T, Yang YX, Wang D, Qiu JX and Zhou SF: Plumbagin induces G2/M arrest, apoptosis, and autophagy via p38 MAPK- and PI3K/Akt/mTOR-mediated pathways in human tongue squamous cell carcinoma cells. Drug Des Devel Ther. 9:1601–1626. 2015.PubMed/NCBI
22	Zou M, Lu N, Hu C, Liu W, Sun Y, Wang X, You Q, Gu C, Xi T and Guo Q: Beclin 1-mediated autophagy in hepatocellular carcinoma cells: implication in anticancer efficiency of oroxylin A via inhibition of mTOR signaling. Cell Signal. 24:1722–1732. 2012. View Article : Google Scholar : PubMed/NCBI
23	Li JP, Yang YX, Liu QL, Zhou ZW, Pan ST, He ZX, Zhang X, Yang T, Pan SY, Duan W, et al: The pan-inhibitor of Aurora kinases danusertib induces apoptosis and autophagy and suppresses epithelial-to-mesenchymal transition in human breast cancer cells. Drug Des Devel Ther. 9:1027–1062. 2015.PubMed/NCBI