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Induction of Autophagy and Inhibition of Oncoprotein Aurora‐A Activity in Curcumin‐Enhanced Chemosensitivity of Grade III Human Bladder Cancer T24 Cells to FDA‐Approved Anticancer Drugs
Author(s) -
Su ChunLi,
Fan YaWen
Publication year - 2015
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.29.1_supplement.752.1
Subject(s) - curcumin , autophagy , atg5 , cancer research , cancer cell , aurora kinase , programmed cell death , pi3k/akt/mtor pathway , kinase , protein kinase b , apoptosis , viability assay , aurora a kinase , chemistry , cancer , pharmacology , medicine , cell cycle , biochemistry
Curcumin is an active anticancer compound in turmeric and curry. Autophagy (programmed cell death type II) is involved in the degradation and recycling of proteins and intracellular components in response to starvation and stress. Aurora‐A is a mitosis‐related serine‐threonine kinase. Overexpression of Aurora‐A increases drug resistance and promotes metastasis of cancer cells. Our previous report showed that curcumin significantly inhibited Aurora‐A gene expression and subsequently kinase activity, which caused failure of various mitotic events and G2/M mitotic arrest in Aurora‐A‐overexpressing human bladder cancer T24 cells. Here we reveal that curcumin enhanced the chemosensitivity of T24 cells to cisplatin plus gemcitabine, the FDA‐approved standard first chemotherapy for patients with locally advanced and metastatic bladder cancer. A decrease in cell viability and the occurrence of a synergy effect were observed. Addition of curcumin promoted apoptosis and G2/M arrest, and decreased Aurora‐A activity. Curcumin‐enhanced chemosensitivity was paralleled by significant increases of autophagy, which were characterized by the expression of autophagy marker LC3‐II using immunoblotting and the formation of acidic vesicular organelles using flow cytometry. Curcumin‐induced autophagy was observed via activation of Raf/MEK/ERK pathway, but not via increase in Atg12‐Atg5 formation or inhibition of AKT/mTOR pathway. Our data suggest a combination of curcumin with the FDA‐approved anticancer drugs for patients with bladder cancer.