Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2013

Open Access 01-12-2013 | Primary research

Apigenin promotes apoptosis, inhibits invasion and induces cell cycle arrest of T24 human bladder cancer cells

Authors: Yi Zhu, Yeqing Mao, Hong Chen, Yiwei Lin, Zhenghui Hu, Jian Wu, Xin Xu, Xianglai Xu, Jie Qin, Liping Xie

Published in: Cancer Cell International | Issue 1/2013

Login to get access

Abstract

Background

Apigenin (4’,5,7-trihydroxyflavone) was recently shown effective in inhibiting several cancers. The aim of this study was to investigate the effect and mechanism of apigenin in the human bladder cancer cell line T24 for the first time.

Methods

T24 cells were treated with varying concentrations and time of apigenin. Cell viability was evaluated by MTT assay. Cell motility and invasiveness were assayed by Matrigel migration and invasion assay. Flow cytometry and western blot analysis were used to detect cell apoptosis, cell cycle and signaling pathway.

Results

The results demonstrated that apigenin suppressed proliferation and inhibited the migration and invasion potential of T24 bladder cancer cells in a dose- and time-dependent manner, which was associated with induced G2/M Phase cell cycle arrest and apoptosis. The mechanism of action is like to involve PI3K/Akt pathway and Bcl-2 family proteins. Apigenin increased caspase-3 activity and PARP cleavage, indicating that apigenin induced apoptosis in a caspase-dependent way.

Conclusions

These findings suggest that apigenin may be an effective way for treating human bladder cancer.
Appendix
Available only for authorised users
Literature
1.
Birt DF, Mitchell D, Gold B, Pour P, Pinch HC: Inhibition of ultraviolet light induced skin carcinogenesis in SKH-1 mice by apigenin, a plant flavonoid. Anticancer Res. 1997, 17 (1A): 85-91.PubMed
2.
Caltagirone S, Rossi C, Poggi A, Ranelletti FO, Natali PG, Brunetti M, Aiello FB, Piantelli M: Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int J Cancer. 2000, 87 (4): 595-600. 10.1002/1097-0215(20000815)87:4<595::AID-IJC21>3.0.CO;2-5.CrossRefPubMed
3.
Wang IK, Lin-Shiau SY, Lin JK: Induction of apoptosis by apigenin and related flavonoids through cytochrome c release and activation of caspase-9 and caspase-3 in leukaemia HL-60 cells. Eur J Cancer. 1999, 35 (10): 1517-1525. 10.1016/S0959-8049(99)00168-9.CrossRefPubMed
4.
Wang W, Heideman L, Chung CS, Pelling JC, Koehler KJ, Birt DF: Cell-cycle arrest at G2/M and growth inhibition by apigenin in human colon carcinoma cell lines. Mol Carcinog. 2000, 28 (2): 102-110. 10.1002/1098-2744(200006)28:2<102::AID-MC6>3.0.CO;2-2.CrossRefPubMed
5.
Yin F, Giuliano AE, Law RE, Van Herle AJ: Apigenin inhibits growth and induces G2/M arrest by modulating cyclin-CDK regulators and ERK MAP kinase activation in breast carcinoma cells. Anticancer Res. 2001, 21 (1A): 413-420.PubMed
6.
Czeczot H, Tudek B, Kusztelak J, Szymczyk T, Dobrowolska B, Glinkowska G, Malinowski J, Strzelecka H: Isolation and studies of the mutagenic activity in the Ames test of flavonoids naturally occurring in medical herbs. Mutat Res. 1990, 240 (3): 209-216. 10.1016/0165-1218(90)90060-F.CrossRefPubMed
7.
Jemal ABF, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61: 69-90. 10.3322/caac.20107.CrossRefPubMed
8.
Weir HK, Thun MJ, Hankey BF, Ries LA, Howe HL, Wingo PA, Jemal A, Ward E, Anderson RN, Edwards BK: Annual report to the nation on the status of cancer, 1975–2000, featuring the uses of surveillance data for cancer prevention and control. J Natl Cancer Inst. 2003, 95 (17): 1276-1299. 10.1093/jnci/djg040.CrossRefPubMed
9.
De Boer EC, De Jong WH, Steerenberg PA, Aarden LA, Tetteroo E, De Groot ER, Van der Meijden AP, Vegt PD, Debruyne FM, Ruitenberg EJ: Induction of urinary interleukin-1 (IL-1), IL-2, IL-6, and tumour necrosis factor during intravesical immunotherapy with bacillus Calmette-Guerin in superficial bladder cancer. Cancer Immunol Immunother. 1992, 34 (5): 306-312. 10.1007/BF01741551.CrossRefPubMed
10.
Lamm DL, Blumenstein BA, Crissman JD, Montie JE, Gottesman JE, Lowe BA, Sarosdy MF, Bohl RD, Grossman HB, Beck TM: Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study. J Urol. 2000, 163 (4): 1124-1129. 10.1016/S0022-5347(05)67707-5.CrossRefPubMed
11.
Qin J, Xie LP, Zheng XY, Wang YB, Bai Y, Shen HF, Li LC, Dahiya R: A component of green tea, (-)-epigallocatechin-3-gallate, promotes apoptosis in T24 human bladder cancer cells via modulation of the PI3K/Akt pathway and Bcl-2 family proteins. Biochem Biophys Res Commun. 2007, 354 (4): 852-857. 10.1016/j.bbrc.2007.01.003.CrossRefPubMed
12.
Bai Y, Mao QQ, Qin J, Zheng XY, Wang YB, Yang K, Shen HF, Xie LP: Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo. Cancer Sci. 2010, 101 (2): 488-493. 10.1111/j.1349-7006.2009.01415.x.CrossRefPubMed
13.
Boatright KM, Salvesen GS: Mechanisms of caspase activation. Curr Opin Cell Biol. 2003, 15 (6): 725-731. 10.1016/j.ceb.2003.10.009.CrossRefPubMed
14.
Franke TF, Hornik CP, Segev L, Shostak GA, Sugimoto C: PI3K/Akt and apoptosis: size matters. Oncogene. 2003, 22 (56): 8983-8998. 10.1038/sj.onc.1207115.CrossRefPubMed
15.
Pugazhenthi S, Nesterova A, Sable C, Heidenreich KA, Boxer LM, Heasley LE, Reusch JE: Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. J Biol Chem. 2000, 275 (15): 10761-10766. 10.1074/jbc.275.15.10761.CrossRefPubMed
16.
Vivanco I, Sawyers CL: The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2002, 2 (7): 489-501. 10.1038/nrc839.CrossRefPubMed
17.
Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 1997, 91 (2): 231-241. 10.1016/S0092-8674(00)80405-5.CrossRefPubMed
18.
Cardone MH, Roy N, Stennicke HR, Salvesen GS, Franke TF, Stanbridge E, Frisch S, Reed JC: Regulation of cell death protease caspase-9 by phosphorylation. Science. 1998, 282 (5392): 1318-1321.CrossRefPubMed
19.
Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME: Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999, 96 (6): 857-868. 10.1016/S0092-8674(00)80595-4.CrossRefPubMed
20.
Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB: NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature. 1999, 401 (6748): 82-85. 10.1038/43466.CrossRefPubMed
21.
Romashkova JA, Makarov SS: NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. Nature. 1999, 401 (6748): 86-90. 10.1038/43474.CrossRefPubMed
22.
Ahmed NN, Grimes HL, Bellacosa A, Chan TO, Tsichlis PN: Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase. Proc Natl Acad Sci U S A. 1997, 94 (8): 3627-3632. 10.1073/pnas.94.8.3627.PubMedCentralCrossRefPubMed
23.
Medema RH, Kops GJ, Bos JL, Burgering BM: AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature. 2000, 404 (6779): 782-787. 10.1038/35008115.CrossRefPubMed
24.
Masuelli L, Marzocchella L, Quaranta A, Palumbo C, Pompa G, Izzi V, Canini A, Modesti A, Galvano F, Bei R: Apigenin induces apoptosis and impairs head and neck carcinomas EGFR/ErbB2 signaling. Front Biosci. 2011, 16: 1060-1068. 10.2741/3735.CrossRef
25.
Asnaghi L, Calastretti A, Bevilacqua A, D'Agnano I, Gatti G, Canti G, Delia D, Capaccioli S, Nicolin A: Bcl-2 phosphorylation and apoptosis activated by damaged microtubules require mTOR and are regulated by Akt. Oncogene. 2004, 23 (34): 5781-5791. 10.1038/sj.onc.1207698.CrossRefPubMed
26.
Chan TO, Rittenhouse SE, Tsichlis PN: AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation. Annu Rev Biochem. 1999, 68: 965-1014. 10.1146/annurev.biochem.68.1.965.CrossRefPubMed
27.
Brown GC, Borutaite V: Nitric oxide, cytochrome c and mitochondria. Biochem Soc Symp. 1999, 66: 17-25.CrossRefPubMed
28.
Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X: Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 1997, 275 (5303): 1129-1132. 10.1126/science.275.5303.1129.CrossRefPubMed
29.
King KL, Cidlowski JA: Cell cycle regulation and apoptosis. Annu Rev Physiol. 1998, 60: 601-617. 10.1146/annurev.physiol.60.1.601.CrossRefPubMed
30.
Pan J, She M, Xu ZX, Sun L, Yeung SC: Farnesyltransferase inhibitors induce DNA damage via reactive oxygen species in human cancer cells. Cancer Res. 2005, 65 (9): 3671-3681. 10.1158/0008-5472.CAN-04-2744.CrossRefPubMed
31.
Lepley DM, Li B, Birt DF, Pelling JC: The chemopreventive flavonoid apigenin induces G2/M arrest in keratinocytes. Carcinogenesis. 1996, 17 (11): 2367-2375. 10.1093/carcin/17.11.2367.CrossRefPubMed
32.
Lepley DM, Pelling JC: Induction of p21/WAF1 and G1 cell-cycle arrest by the chemopreventive agent apigenin. Mol Carcinog. 1997, 19 (2): 74-82. 10.1002/(SICI)1098-2744(199707)19:2<74::AID-MC2>3.0.CO;2-L.CrossRefPubMed
33.
Lee SRPJ, Park EK, Chung CH, Kang SS, Bang OS: Akt-induced promotion of cell-cycle progression at G2/M phase involves upregulation of NF-Y binding activity in PC12 cells. J Cell Physiol. 2005, 205 (2): 270-277. 10.1002/jcp.20395.CrossRefPubMed
34.
Albini A, Iwamoto Y, Kleinman HK, Martin GR, Aaronson SA, Kozlowski JM, McEwan RN: A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res. 1987, 47 (12): 3239-3245.PubMed
Metadata
Title
Apigenin promotes apoptosis, inhibits invasion and induces cell cycle arrest of T24 human bladder cancer cells
Authors
Yi Zhu
Yeqing Mao
Hong Chen
Yiwei Lin
Zhenghui Hu
Jian Wu
Xin Xu
Xianglai Xu
Jie Qin
Liping Xie
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2013
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-13-54

Other articles of this Issue 1/2013

Cancer Cell International 1/2013 Go to the issue

Primary research

Hydrogen peroxide (H2O2) induces leukemic but not normal hematopoietic cell death in a dose-dependent manner

Review

Acidic extracellular microenvironment and cancer

Primary research

TLR9 signaling repressed tumor suppressor miR-7 expression through up-regulation of HuR in human lung cancer cells

Primary research

Functional disruption of macrophage migration inhibitory factor (MIF) suppresses proliferation of human H460 lung cancer cells by caspase-dependent apoptosis

Primary research

Promoter methylation status of the tumor suppressor gene SOX11 is associated with cell growth and invasion in nasopharyngeal carcinoma

Primary research

Positive association between Interleukin-8 -251A > T polymorphism and susceptibility to gastric carcinogenesis: a meta-analysis
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits