title: Synergistic effect of fenretinide and curcumin for treatment of non-small cell lung cancer.
abstract: Curcumin and fenretinide are 2 well-known and promising chemotherapeutic compounds via various molecular mechanisms. However, the anticancer capacity of either curcumin or fenretinide is limited. This prompted us to examine the combined anticancer effects of curcumin and fenretinide. Our results demonstrate for the first time that there is synergistic anticancer effect of combined treatment with these 2 agents, leading to enhanced cytotoxicity and enhanced expression level of pro-apoptotic protein cleaved PARP in non-small cell lung cancer (NSCLC) cells while showed little toxicity to rat cardiomyoblast normal cells. The combination treatment was also demonstrated to inhibit lung carcinoma growth in vivo. Furthermore, we show that fenretinide or the ER stress inhibitor 4-PBA decreased curcumin-induced Glucose-regulated protein 78 (GRP78) upregulation, and produced a similar enhanced cytotoxic effect. In addition, GRP78 knockdown by siRNA also enhanced the cytotoxic effect of curcumin in A549 and H1299 cells. Our findings suggest that the 2 small molecules, when used in combination, can potentially be effective therapeutic agents for treating NSCLC, at least in part, by regulating endoplasmic reticulum (ER) chaperone protein GRP78.
authors.affiliation: a State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau , Macau , China.
authors.forename: Huanxian
authors.initials: H
authors.lastname: Chen
authors.affiliation: a State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau , Macau , China.
authors.forename: Linmin
authors.initials: L
authors.lastname: Chen
authors.affiliation: a State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau , Macau , China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau , Macau , China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhou
authors.affiliation: a State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau , Macau , China.
authors.forename: Judy Yuet-Wa
authors.initials: JY
authors.lastname: Chan
authors.affiliation: a State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau , Macau , China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: a State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau , Macau , China.|b Department of Bioengineering, Zhuhai Key Laboratory of Fundamental and Applied Research in Traditional Chinese Medicine , Zhuhai Campus of Zunyi Medical College , Zhuhai , China.
authors.forename: Guozhen
authors.initials: G
authors.lastname: Cui
authors.affiliation: a State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau , Macau , China.
authors.forename: Simon Ming-Yuen
authors.initials: SM
authors.lastname: Lee
keywords: Curcumin; GRP78; fenretinide; non-small cell lung cancer