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 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Evaluation of a curcumin analog as an anti-cancer agent inducing ER stress-mediated apoptosis in non-small cell lung cancer cells

Authors: Zhiguo Liu, Yusheng Sun, Luqing Ren, Yi Huang, Yuepiao Cai, Qiaoyou Weng, Xueqian Shen, Xiaokun Li, Guang Liang, Yi Wang

Published in: BMC Cancer | Issue 1/2013

Login to get access

Abstract

Background

Recent advances have highlighted the importance of the endoplasmic reticulum (ER) in cell death processes. Pharmacological interventions that effectively enhance tumor cell death through activating ER stress have attracted a great deal of attention for anti-cancer therapy.

Methods

A bio-evaluation on 113 curcumin analogs against four cancer cell lines was performed through MTT assay. Furthermore, real time cell assay and flow cytometer were used to evaluate the apoptotic induction of (1E,4E)-1,5-bis(5-bromo-2-ethoxyphenyl)penta-1,4-dien-3-one (B82). Western blot, RT-qPCR, and siRNA were then utilized to confirm whether B82-induced apoptosis is mediated through activating ER stress pathway. Finally, the in vivo anti-tumor effect of B82 was evaluated.

Results

B82 exhibited strong anti-tumor activity in non-small cell lung cancer (NSCLC) H460 cells. Treatment with B82 significantly induced apoptosis in H460 cells in vitro and inhibited H460 tumor growth in vivo. Further studies demonstrated that the B82-induced apoptosis is mediated by activating ER stress both in vitro and in vivo.

Conclusions

A new monocarbonyl analog of curcumin, B82, exhibited anti-tumor effects on H460 cells via an ER stress-mediated mechanism. B82 could be further explored as a potential anticancer agent for the treatment of NSCLC.
Appendix
Available only for authorised users
Literature
1.
2.
Sun SH, Huang HC, Huang C, Lin JK: Cycle arrest and apoptosis in MDA-MB-231/Her2 cells induced by curcumin. Eur J Pharmacol. 2012, 690 (1–3): 22-30.CrossRefPubMed
3.
Ng AP, Chng WJ, Khan M: Curcumin sensitizes acute promyelocytic leukemia cells to unfolded protein response-induced apoptosis by blocking the loss of misfolded N-CoR protein. Mol Cancer Res. 2011, 9 (7): 878-888. 10.1158/1541-7786.MCR-10-0545.CrossRefPubMed
4.
Wu SH, Hang LW, Yang JS, Chen HY, Lin HY, Chiang JH, Lu CC, Yang JL, Lai TY, Ko YC, et al: Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pathways. Anticancer Res. 2010, 30 (6): 2125-2133.PubMed
5.
Wang L, Song R, Shen Y, Sun Y, Gu Y, Shu Y, Xu Q: Targeting sarcoplasmic/endoplasmic reticulum Ca(2) + -ATPase 2 by curcumin induces ER stress-associated apoptosis for treating human liposarcoma. Mol Cancer Ther. 2011, 10 (3): 461-471. 10.1158/1535-7163.MCT-10-0812.CrossRefPubMed
6.
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB: Bioavailability of curcumin: problems and promises. Mol Pharm. 2007, 4 (6): 807-818. 10.1021/mp700113r.CrossRefPubMed
7.
Liang G, Yang S, Zhou H, Shao L, Huang K, Xiao J, Huang Z, Li X: Synthesis, crystal structure and anti-inflammatory properties of curcumin analogues. Eur J Med Chem. 2009, 44 (2): 915-919. 10.1016/j.ejmech.2008.01.031.CrossRefPubMed
8.
Liang G, Zhou H, Wang Y, Gurley EC, Feng B, Chen L, Xiao J, Yang S, Li X: Inhibition of LPS-induced production of inflammatory factors in the macrophages by mono-carbonyl analogues of curcumin. J Cell Mol Med. 2009, 13 (9B): 3370-3379. 10.1111/j.1582-4934.2009.00711.x.CrossRefPubMedPubMedCentral
9.
Zhao C, Yang J, Wang Y, Liang D, Yang X, Li X, Wu J, Wu X, Yang S, Liang G: Synthesis of mono-carbonyl analogues of curcumin and their effects on inhibition of cytokine release in LPS-stimulated RAW 264.7 macrophages. Bioorg Med Chem. 2010, 18 (7): 2388-2393. 10.1016/j.bmc.2010.03.001.CrossRefPubMed
10.
Zhao C, Cai Y, He X, Li J, Zhang L, Wu J, Zhao Y, Yang S, Li X, Li W, et al: Synthesis and anti-inflammatory evaluation of novel mono-carbonyl analogues of curcumin in LPS-stimulated RAW 264.7 macrophages. Eur J Med Chem. 2010, 45 (12): 5773-5780. 10.1016/j.ejmech.2010.09.037.CrossRefPubMed
11.
Wu J, Li J, Cai Y, Pan Y, Ye F, Zhang Y, Zhao Y, Yang S, Li X, Liang G: Evaluation and discovery of novel synthetic chalcone derivatives as anti-inflammatory agents. J Med Chem. 2011, 54 (23): 8110-8123. 10.1021/jm200946h.CrossRefPubMed
12.
Liang G, Li X, Chen L, Yang S, Wu X, Studer E, Gurley E, Hylemon PB, Ye F, Li Y, et al: Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin. Bioorg Med Chem Lett. 2008, 18 (4): 1525-1529. 10.1016/j.bmcl.2007.12.068.CrossRefPubMedPubMedCentral
13.
Liang G, Shao LL, Wang Y, Zhao CG, Chu YH, Xiao J, Zhao Y, Li XK, Yang SL: Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents. Bioorg Med Chem. 2009, 17 (6): 2623-2631. 10.1016/j.bmc.2008.10.044.CrossRefPubMed
14.
Han J, Murthy R, Wood B, Song B, Wang S, Sun B, Malhi H, Kaufman RJ: ER stress signalling through eIF2alpha and CHOP, but not IRE1alpha, attenuates adipogenesis in mice. Diabetologia. 2013, 56 (4): 911-924. 10.1007/s00125-012-2809-5.CrossRefPubMedPubMedCentral
15.
Hammadi M, Oulidi A, Gackiere F, Katsogiannou M, Slomianny C, Roudbaraki M, Dewailly E, Delcourt P, Lepage G, Lotteau S, et al: Modulation of ER stress and apoptosis by endoplasmic reticulum calcium leak via translocon during unfolded protein response: involvement of GRP78. FASEB J. 2013
16.
Wang X, Thomas B, Sachdeva R, Arterburn L, Frye L, Hatcher PG, Cornwell DG, Ma J: Mechanism of arylating quinone toxicity involving Michael adduct formation and induction of endoplasmic reticulum stress. Proc Natl Acad Sci U S A. 2006, 103 (10): 3604-3609. 10.1073/pnas.0510962103.CrossRefPubMedPubMedCentral
17.
Wang Y, Xiao J, Zhou H, Yang S, Wu X, Jiang C, Zhao Y, Liang D, Li X, Liang G: A Novel Monocarbonyl Analogue of Curcumin, (1E,4E)-1,5-Bis(2,3-dimethoxyphenyl)penta-1,4-dien-3-one, Induced Cancer Cell H460 apoptosis via activation of endoplasmic reticulum stress signaling pathway. J Med Chem. 2011, 54 (11): 3768-3778. 10.1021/jm200017g.CrossRefPubMed
18.
Kilbride SM, Prehn JH: Central roles of apoptotic proteins in mitochondrial function. Oncogene. 2013, 32 (22): 2703-2711. 10.1038/onc.2012.348.CrossRefPubMed
Metadata
Title
Evaluation of a curcumin analog as an anti-cancer agent inducing ER stress-mediated apoptosis in non-small cell lung cancer cells
Authors
Zhiguo Liu
Yusheng Sun
Luqing Ren
Yi Huang
Yuepiao Cai
Qiaoyou Weng
Xueqian Shen
Xiaokun Li
Guang Liang
Yi Wang
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-494

Other articles of this Issue 1/2013

BMC Cancer 1/2013 Go to the issue

Research article

Overexpression of peptide deformylase in breast, colon, and lung cancers

Research article

Elevated cyclin B2 expression in invasive breast carcinoma is associated with unfavorable clinical outcome

Research article

Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series

Research article

Intensity-modulated radiotherapy versus radical prostatectomy in patients with localized prostate cancer: long-term follow-up

Research article

Expression of follicle-stimulating hormone receptor by the vascular endothelium in tumor metastases

Research article

Indirectly estimated absolute lung cancer mortality rates by smoking status and histological type based on a systematic review
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