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A Novel Mono‐carbonyl Analogue of Curcumin Induces Apoptosis by Activating ER Stress in Non‐Small Lung Cancer Cells
Author(s) -
Xiao Jian,
Liang Guang,
Huang Yi,
Li Xiaokun,
Studer Elaine,
Zhou Huiping
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.703.14
Subject(s) - curcumin , apoptosis , unfolded protein response , chemistry , chop , downregulation and upregulation , mtt assay , western blot , flow cytometry , cancer research , pharmacology , lung cancer , microbiology and biotechnology , biochemistry , medicine , biology , gene
Non‐small lung cancer (NSCLC) is one of the most common cancers worldwide. Curcumin, a well‐known food additive and constituent of traditional medicine, has been used to treat several different cancers including NSCLC in clinical trials. However, its poor bioavailability and pharmacokinetic profiles due to its instability under physiological conditions have limited its application in anti‐cancer therapies. In this study, we synthesized a novel mono‐carbonyl analogue of curcumin, (1E,4E)‐1,5‐bis (2‐methoxyphenyl) penta‐1,4‐dien‐3‐one (B63), and examined its proapoptotic effect in NSCLC cells. Methods H460 or H358 cells were treated with different amounts of curcumin and B63 for various time periods. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry. The activation of ER stress was determined by Western blot analysis. The ER Ca2+ content was measured using the fluorescent Ca2+ indicator fura 2/AM. Lentiviral shRNA was used to knock down the ER stress responsive gene CHOP. Results B63 had better bioavailability and more potent proapoptotic activity than curcumin. B63, not curcumin, significantly induced depletion of ER Ca2+ store and activation of the unfolded protein response (UPR). Downregulation of CHOP expression inhibited B63‐induced apoptosis. Conclusion Activation of the UPR represents a key molecular mechanism underlying B63‐induced apoptosis in NSCLC cells.