Effect of luteolin on apoptosis and vascular endothelial growth factor in human choroidal melanoma cells
Author:
Corresponding Author:

Hong-Fei Liao. Department of Ophthalmology, the Affiliated Eye Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China. lhfzf@126.com

  • Article
  • | |
  • Metrics
  • |
  • Reference [22]
  • |
  • Related [20]
  • | | |
  • Comments
    Abstract:

    AIM: To investigate the effects of luteolin on apoptosis, the cell cycle, and the expression and secretion of vascular endothelial growth factor (VEGF) in human choroidal melanoma cells (C918 and OCM-1). METHODS: C918 and OCM-1 cells cultured in vitro were treated with various concentrations of luteolin (0, 5, 10, 15 μmol/L). Cell growth was observed with an inverted microscope, and cell cycle arrest was detected by propidium iodide (PI) staining using flow cytometry. Apoptosis was detected by Hoechst33342 staining, and apoptosis rate was determined by Annexin V-FITC/PI experiments using flow cytometry. The expression of apoptosis-related proteins Bcl-2, Bax and VEGF was analyzed using Western blots. The levels of VEGF secreted by the cells into the supernatant was analyzed using ELISA. RESULTS: After treating with 5 to 15 μmol/L luteolin for 48h, the fusion degree of C918 and OCM-1 cells decreased, and more floating apoptotic cells appeared. Luteolin treatment increased the G0-G1 phase ratio of the C918 and OCM-1 cells, blocked cell cycle progression, and increased the apoptosis rate of the C918 and OCM-1 cells. Western blot showed that luteolin decreased the expression of Bcl-2 and VEGF in the C918 and OCM-1 cells and increased the expression of Bax protein. The ELISA results showed that 10 to 15 μmol/L luteolin decreased the cell secretion of VEGF. CONCLUSION: Luteolin may induce apoptosis by regulating the levels of apoptosis-related proteins in C918 and OCM-1 cells. Luteolin can induce cell cycle arrest, decrease the expression of VEGF.

    Reference
    1 Chattopadhyay C, Kim DW, Gombos DS, Oba J, Qin Y, Williams MD, Esmaeli B, Grimm EA, Wargo JA, Woodman SE, Patel SP. Uveal melanoma: from diagnosis to treatment and the science in between. Cancer 2016;122(15):2299-2312.
    2 Spagnolo F, Caltabiano G, Queirolo P. Uveal melanoma. Cancer Treat Rev 2012;38(5):549-553.
    3 Kaliki S, Shields CL. Uveal melanoma: relatively rare but deadly cancer. Eye (Lond) 2017;31(2):241-257.
    4 Bagger M, Smidt-Nielsen I, Andersen MK, Jensen PK, Heegaard S, Andersen KK, Friis S, Kiilgaard JF. Long-term metastatic risk after biopsy of posterior uveal melanoma. Ophthalmology 2018;125(12):1969-1976.
    5 Dai LM, Chen H, Li WP, Liu SQ, Chen MZ, Xu SY. The influence of luteolin on experimental inflammatory model in rat. Acta Universitatis Medicinalis Anhui 1985;20(1):3-5.
    6 Zhao WZ, Xu LH, Li WP, Chen MZ, Xu SY. Inhibitory effect of luteolin on ear inflammation induced by dimethyl benzene in mice. Acta Universitatis Medicinalis Anhui 1985;20(1):13-15.
    7 Imran M, Rauf A, Abu-Izneid T, Nadeem M, Shariati MA, Khan IA, Imran A, Orhan IE, Rizwan M, Atif M, Gondal TA, Mubarak MS. Luteolin, a flavonoid, as an anticancer agent: a review. Biomed Pharmacother 2019;112:108612.
    8 Alkharsah KR. VEGF upregulation in viral infections and its possible therapeutic implications. Int J Mol Sci 2018;19(6):E1642.
    9 Peng KW, Bai Y, Zhu QH, Hu B, Xu YG. Targeting VEGF-neuropilin interactions: a promising antitumor strategy. Drug Discov Today 2019;24(2):656-664.
    10 Zubilewicz A, Hecquet C, Jeanny JC, Soubrane G, Courtois Y, Mascarelli F. Two distinct signalling pathways are involved in FGF2-stimulated proliferation of choriocapillary endothelial cells: a comparative study with VEGF. Oncogene 2001;20(12):1403-1413.
    11 Xu XY, Zong Y, Gao YX, Sun XR, Zhao H, Luo WJ, Jia SY. VEGF induce vasculogenic mimicry of choroidal melanoma through the PI3k signal pathway. Biomed Res Int 2019;2019:3909102.
    12 Ahmadi A, Shadboorestan A. Oxidative stress and cancer; the role of hesperidin, a citrus natural bioflavonoid, as a cancer chemoprotective agent. Nutr Cancer 2016;68(1):29-39.
    13 Arora R, Bharti V, Gaur P, Aggarwal S, Mittal M, Das SN. Operculina turpethum extract inhibits growth and proliferation by inhibiting NF-κB, COX-2 and cyclin D1 and induces apoptosis by up regulating P53 in oral cancer cells. Arch Oral Biol 2017;80:1-9.
    14 Ceci C, Lacal P, Tentori L, de Martino M, Miano R, Graziani G. Experimental evidence of the antitumor, antimetastatic and antiangiogenic activity of ellagic acid. Nutrients 2018;10(11):1756.
    15 Horinaka M, Yoshida T, Shiraishi T, Nakata S, Wakada M, Nakanishi R, Nishino H, Matsui H, Sakai T. Luteolin induces apoptosis via death receptor 5 upregulation in human malignant tumor cells. Oncogene 2005;24(48):7180-7189.
    16 Yang MY, Wang CJ, Chen NF, Ho WH, Lu FJ, Tseng TH. Luteolin enhances paclitaxel-induced apoptosis in human breast cancer MDA-MB-231 cells by blocking STAT3. Chem Biol Interact 2014;213:60-68.
    17 Choi AY, Choi JH, Yoon H, Hwang KY, Noh MH, Choe W, Yoon KS, Ha J, Yeo EJ, Kang I. Luteolin induces apoptosis through endoplasmic reticulum stress and mitochondrial dysfunction in Neuro-2a mouse neuroblastoma cells. Eur J Pharmacol 2011;668(1-2):115-126.
    18 Bai LC, Chen JF, McEachern D, Liu L, Zhou HB, Aguilar A, Wang SM. BM-1197: a novel and specific Bcl-2/Bcl-xL inhibitor inducing complete and long-lasting tumor regression in vivo. PLoS One 2014;9(6):e99404.
    19 Oltvai ZN, Korsmeyer SJ. Checkpoints of dueling dimers foil death wishes. Cell 1994;79(2):189-192.
    20 Park SH, Ham S, Kwon TH, Kim MS, Lee DH, Kang JW, Oh SR, Yoon DY. Luteolin induces cell cycle arrest and apoptosis through extrinsic and intrinsic signaling pathways in MCF-7 breast cancer cells. J Environ Pathol Toxicol Oncol 2014;33(3):219-231.
    21 Tsai YD, Chen HJ, Hsu HF, Lu K, Liang CL, Liliang PC, Wang KW, Wang HK, Wang CP, Houng JY. Luteolin inhibits proliferation of human glioblastoma cells via induction of cell cycle arrest and apoptosis. Journal of the Taiwan Institute of Chemical Engineers 2013;44(6):837-845.
    22 Chen P, Zhang JY, Sha BB, Ma YE, Hu T, Ma YC, Sun H, Shi JX, Dong ZM, Li P. Luteolin inhibits cell proliferation and induces cell apoptosis via down-regulation of mitochondrial membrane potential in esophageal carcinoma cells EC1 and KYSE450. Oncotarget 2017;8(16):27471-27480.
    Cited by
    Comments
    Comments
    分享到微博
    Submit
Get Citation

Meng-Lin Shi, Yu-Fen Chen, Hong-Fei Liao. ,/et al.Effect of luteolin on apoptosis and vascular endothelial growth factor in human choroidal melanoma cells. Int J Ophthalmol, 2021,14(2):186-193

Copy
Share
Article Metrics
  • Abstract:1189
  • PDF: 853
  • HTML: 0
  • Cited by: 0
Publication History
  • Received:August 09,2020
  • Revised:October 12,2020
  • Online: December 24,2020