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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

BPIQ, a novel synthetic quinoline derivative, inhibits growth and induces mitochondrial apoptosis of lung cancer cells in vitro and in zebrafish xenograft model

Authors: Chien-Chih Chiu, Han-Lin Chou, Bing-Hung Chen, Kuo-Feng Chang, Chih-Hua Tseng, Yao Fong, Tzu-Fun Fu, Hsueh-Wei Chang, Chang-Yi Wu, Eing-Mei Tsai, Shinne-Ren Lin, Yeh-Long Chen

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

2,9-Bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy] phenyl}-11H-indeno[1,2-c]quinolin-11-one (BPIQ) is a derivative from 6-arylindeno[1,2-c]quinoline. Our previous study showed the anti-cancer potential of BPIQ compared to its two analogues topotecan and irinotecan. In the study, the aim is to investigate the potency and the mechanism of BPIQ against lung cancer cells.

Methods

Both in vitro and zebrafish xenograft model were performed to examine the anti-lung cancer effect of BPIQ. Flow cytometer-based assays were performed for detecting apoptosis and cell cycle distribution. Western blot assay was used for detecting the changes of apoptotic and cell cycle-associated proteins. siRNA knockdown assay was performed for confirming the apoptotic role of Bim.

Results

Both in vitro and zebrafish xenograft model demonstrated the anti-lung cancer effect of BPIQ. BPIQ-induced proliferative inhibition of H1299 cells was achieved through the induction of G2/M-phase arrest and apoptosis. The results of Western blot showed that BPIQ-induced G2/M-phase arrest was associated with a marked decrease in the protein levels of cyclin B and cyclin-dependent kinase 1 (CDK1). The up-regulation of pro-apoptotic Bad, Bim and down-regulation of pro-survival XIAP and survivin was observed following BPIQ treatment.

Conclusions

BPIQ-induced anti-lung cancer is involved in mitochondrial apoptosis. BPIQ could be a promising anti-lung cancer drug for further applications.
Appendix
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Literature
1.
Tseng RC, Lee CC, Hsu HS, Tzao C, Wang YC. Distinct HIC1-SIRT1-p53 loop deregulation in lung squamous carcinoma and adenocarcinoma patients. Neoplasia. 2009;11(8):763–70.CrossRefPubMedPubMedCentral
2.
Pirker R, Minar W. Chemotherapy of advanced non-small cell lung cancer. Front Radiat Ther On. 2010;42:157–63.CrossRef
3.
Wagner TD, Yang GY. The role of chemotherapy and radiation in the treatment of locally advanced non-small cell lung cancer (NSCLC). Curr Drug Targets. 2010;11(1):67–73.CrossRefPubMed
4.
O'Rourke N, Roque IFM, Farre Bernado N, Macbeth F. Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev. 2010;6:CD002140.PubMed
5.
Ettinger DS, Akerley W, Bepler G, Blum MG, Chang A, Cheney RT, et al. Non-small cell lung cancer. J Natl Compr Canc Netw. 2010;8(7):740–801.PubMed
6.
Elbaz HA, Stueckle TA, Wang HY, O'Doherty GA, Lowry DT, Sargent LM, et al. Digitoxin and a synthetic monosaccharide analog inhibit cell viability in lung cancer cells. Toxicol Appl Pharm. 2012;258(1):51–60.CrossRef
7.
Kumar S, Bawa S, Gupta H. Biological activities of quinoline derivatives. Mini Rev Med Chem. 2009;9(14):1648–54.CrossRefPubMed
8.
Schulze-Topphoff U, Shetty A, Varrin-Doyer M, Molnarfi N, Sagan SA, Sobel RA, et al. Laquinimod, a quinoline-3-carboxamide, induces type II myeloid cells that modulate central nervous system autoimmunity. PLoS One. 2012;7(3):e33797.CrossRefPubMedPubMedCentral
9.
Tseng CH, Tzeng CC, Yang CL, Lu PJ, Chen HL, Li HY, et al. Synthesis and antiproliferative evaluation of certain indeno[1,2-c]quinoline derivatives. Part 2. J Med Chem. 2010;53(16):6164–79.CrossRefPubMed
10.
11.
Tseng CH, Chen YL, Lu PJ, Yang CN, Tzeng CC. Synthesis and antiproliferative evaluation of certain indeno[1,2-c]quinoline derivatives. Bioorg Med Chem. 2008;16(6):3153–62.CrossRefPubMed
12.
Shenoy S, Vasania VS, Gopal M, Mehta A. 8-Methyl-4-(3-diethylaminopropylamino) pyrimido [4',5';4,5] thieno (2,3-b) quinoline (MDPTQ), a quinoline derivate that causes ROS-mediated apoptosis in leukemia cell lines. Toxicol Appl Pharm. 2007;222(1):80–8.CrossRef
13.
Wall ME, Wani MC. Camptothecin and taxol: from discovery to clinic. J Ethnopharmacol. 1996;51(1–3):239–53.CrossRefPubMed
14.
15.
Pommier Y. Topoisomerase I, inhibitors: Camptothecins and beyond. Nat Rev Cancer. 2006;6(10):789–802.CrossRefPubMed
16.
Tseng CH, Chen YL, Chung KY, Cheng CM, Wang CH, Tzeng CC. Synthesis and antiproliferative evaluation of 6-arylindeno [1, 2-c] quinoline derivatives. Bioorg Med Chem. 2009;17(21):7465–76.CrossRefPubMed
17.
Park SH, Cho EK, Kim Y, Kyung SY, An CH, Lee SP, et al. Salvage treatment with topotecan in patients with irinotecan-refractory small cell lung cancer. Cancer Chemoth Pharm. 2008;62(6):1009–14.CrossRef
18.
Wirth M, Berthold E, Grashoff M, Pfutzner H, Schubert U, Hauser H. Detection of mycoplasma contaminations by the polymerase chain reaction. Cytotechnology. 1994;16(2):67–77.CrossRefPubMed
19.
Chiu CC, Liu PL, Huang KJ, Wang HM, Chang KF, Chou CK, et al. Goniothalamin inhibits growth of human lung cancer cells through DNA damage, apoptosis, and reduced migration ability. J Agric Food Chem. 2011;59(8):4288–93.CrossRefPubMed
20.
Chiu CC, Chen JY, Lin KL, Huang CJ, Lee JC, Chen BH, et al. p38 MAPK and NF-kappaB pathways are involved in naphtho[1,2-b] furan-4,5-dione induced anti-proliferation and apoptosis of human hepatoma cells. Cancer Lett. 2010;295(1):92–9.CrossRefPubMed
21.
Chakraborty C, Hsu CH, Wen ZH, Lin CS, Agoramoorthy G. Zebrafish: A complete animal model for in vivo drug discovery and development. Curr Drug Metab. 2009;10(2):116–24.CrossRefPubMed
22.
Delvecchio C, Tiefenbach J, Krause HM. The zebrafish: A powerful platform for in vivo, HTS drug discovery. Assay Drug Dev Technol. 2011;9(4):354–61.CrossRefPubMed
23.
Tat J, Liu M, Wen XY. Zebrafish cancer and metastasis models for in vivo drug discovery. Drug Discov Today Technol. 2013;10(1):e83–89.CrossRefPubMed
24.
Cho YS, Jung HJ, Seok SH, Payumo AY, Chen JK, Kwon HJ. Functional inhibition of UQCRB suppresses angiogenesis in zebrafish. Biochem Biophys Res Commun. 2013;433(4):396–400.CrossRefPubMedPubMedCentral
25.
Wilkinson RW, Odedra R, Heaton SP, Wedge SR, Keen NJ, Crafter C, et al. AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis. Clin Cancer Res. 2007;13(12):3682–8.CrossRefPubMed
26.
Sliwinska MA, Mosieniak G, Wolanin K, Babik A, Piwocka K, Magalska AS, et al. Induction of senescence with doxorubicin leads to increased genomic instability of HCT116 cells. Mech Ageing Dev. 2009;130(1–2):24–32.CrossRefPubMed
27.
Chang JH, Kwon HY. Expression of 14-3-3delta, cdc2 and cyclin B proteins related to exotoxin A-induced apoptosis in HeLa S3 cells. Int Immunopharmacol. 2007;7(9):1185–91.CrossRefPubMed
28.
Wang T, Lv JH, Zhang XF, Li CJ, Han X, Sun YJ. Tissue inhibitor of metalloproteinase-1 protects MCF-7 breast cancer cells from paclitaxel-induced apoptosis by decreasing the stability of cyclin B1. Int J Cancer. 2010;126(2):362–70.CrossRefPubMed
29.
Narayan S, Chandra J, Sharma M, Naithani R, Sharma S. Expression of apoptosis regulators Bcl-2 and Bax in childhood acute lymphoblastic leukemia. Hematology. 2007;12(1):39–43.CrossRefPubMed
30.
Zecchin KG, Seidinger AL, Chiaratti MR, Degasperi GR, Meirelles FV, Castilho RF, et al. High Bcl-2/Bax ratio in Walker tumor cells protects mitochondria but does not prevent H2O2-induced apoptosis via calcineurin pathways. J Bioenerg Biomembr. 2007;39(2):186–94.CrossRefPubMed
31.
Saed GM, Jiang Z, Fletcher NM, Diamond MP. Modulation of the BCL-2/BAX ratio by interferon-gamma and hypoxia in human peritoneal and adhesion fibroblasts. Fertil Steril. 2008;90(5):1925–30.CrossRefPubMed
32.
Lee SH, Park SM, Park JH, Shin DY, Kim GY, Ryu CH, et al. Induction of apoptosis in human leukemia U937 cells by anthocyanins through down-regulation of Bcl-2 and activation of caspases. Int J Oncol. 2009;34(4):1077–83.PubMed
33.
Zhao YN, Guo X, Ma ZG, Gu L, Ge J, Li Q. Pro-apoptotic protein BIM in apoptosis of glucocorticoid-sensitive and -resistant acute lymphoblastic leukemia CEM cells. Med Oncol. 2010;28(4):1609–17.CrossRefPubMed
34.
Gang Z, Lai-yun F. Effect of matrine on apoptosis and Bad expression of colorectal cancer cells in vitro. Chongqing Med. 2009;38(8):925–7.
35.
Carrasco RA, Stamm NB, Marcusson E, Sandusky G, Iversen P, Patel BKR. Antisense inhibition of survivin expression as a cancer therapeutic. Mol Cancer Ther. 2011;10(2):221.CrossRefPubMed
36.
Chanvorachote P, Pongrakhananon V, Wannachaiyasit S, Luanpitpong S, Rojanasakul Y, Nimmannit U. Curcumin sensitizes lung cancer cells to cisplatin-induced apoptosis through superoxide anion-mediated Bcl-2 degradation. Cancer Invest. 2009;27(6):624–35.CrossRefPubMed
37.
Fan J, Li R, Zhang R, Liu HL, Zhang N, Zhang FQ, et al. Effect of Bcl-2 and Bax on survival of side population cells from hepatocellular carcinoma cells. World J Gastroenterol. 2007;13(45):6053–9.CrossRefPubMedPubMedCentral
38.
Salakou S, Kardamakis D, Tsamandas AC, Zolota V, Apostolakis E, Tzelepi V, et al. Increased Bax/Bcl-2 ratio up-regulates caspase-3 and increases apoptosis in the thymus of patients with myasthenia gravis. In Vivo. 2007;21(1):123–32.PubMed
39.
Zielinski RR, Eigl BJ, Chi KN. Targeting the apoptosis pathway in prostate cancer. Cancer J. 2013;19(1):79–89.CrossRefPubMed
Metadata
Title
BPIQ, a novel synthetic quinoline derivative, inhibits growth and induces mitochondrial apoptosis of lung cancer cells in vitro and in zebrafish xenograft model
Authors
Chien-Chih Chiu
Han-Lin Chou
Bing-Hung Chen
Kuo-Feng Chang
Chih-Hua Tseng
Yao Fong
Tzu-Fun Fu
Hsueh-Wei Chang
Chang-Yi Wu
Eing-Mei Tsai
Shinne-Ren Lin
Yeh-Long Chen
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1970-x

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