Curcumin [1,7-Bis(4-hydroxy-3-methoxyphenyl)-1–6-heptadine-3,5-dione; C₂₁H₂₀O₆] Sensitizes Human Prostate Cancer Cells to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand/Apo2L-Induced Apoptosis by Suppressing Nuclear Factor-κB via Inhibition of the Prosurvival Akt Signaling Pathway

Abstract

Our previous studies have shown that dietary pigment curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1-6-heptadine-3,5-dione; C 21 H 20 O 6 ] sensitizes human prostate cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L)-induced apoptosis by inhibiting nuclear factor (NF)-B. In the present study, we demonstrate that activated (phosphorylated) Akt kinase plays a pivotal role in regulation of NF-B and sensitization of LNCaP and PC3 prostate cancer cells to TRAIL by curcumin. Curcumin inhibited the expression of phospho-Akt (p-Akt), which was not due to activation of phosphatase and tensin homolog deleted on chromosome 10 phosphatase activity by curcumin. Because NF-B is a downstream target of Akt, we investigated whether inhibition of NF-B by curcumin is mediated through suppression of p-Akt.

Activation of ATM/Chk1 by curcumin causes cell cycle arrest and apoptosis in human pancreatic cancer cells

“…Inhibition of cell growth and induction of apoptosis is the common mechanism by which curcumin shows its anticancer effects. Accumulating evidence suggests the involvement of multiple-signaling pathways by which curcumin causes growth suppression of human cancer cells (Cheng et al, 2001;Hidaka et al, 2002;Bharti et al, 2003;Kim et al, 2003;Shishodia et al, 2003;Blasius et al, 2006;Lev-Ari et al, 2006;Mitra et al, 2006;Park et al, 2006;Tan et al, 2006;Aggarwal et al, 2007;Aoki et al, 2007;Deeb et al, 2007;Fahey et al, 2007;Lin et al, 2007Lin et al, , 2008Marín et al, 2007;Shankar and Srivastava, 2007;Srivastava et al, 2007;Weir et al, 2007;Binion et al, 2008;Freudlsperger et al, 2008;Ji et al, 2008;Kasinski et al, 2008;Mackenzie et al, 2008;Shankar et al, 2008;Sun et al, 2008). Phase I clinical trials of curcumin demonstrated encouraging chemopreventive effects in patients with high-risk or pre-malignant lesions.…”

Ethanol promotes cytotoxic effects of tumor necrosis factor-related apoptosis-inducing ligand through induction of reactive oxygen species in prostate cancer cells

“…[1][2][3][4][5][6] Within the PCa-derived cell lines studied, androgen-independent PC3 cells are previously shown to be moderately sensitive, and LNCaP cells are reported to be resistant to TRAIL-induced apoptosis. [11][12][13][14][15][16][17][18][19][20] Given the established role of ethanol in inducing cell death, it is a promising agent for promoting tumor cell death in combination with known therapeutic drugs such as TRAIL. Indeed, a critical role for ethanol in promoting apoptotic events in various cell lines and animal models has been well documented.…”

“…[7][8][9] Interestingly, resistance to TRAIL by PCa cells can be overcome when TRAIL is combined with various chemotherapeutic agents. [10][11][12][13][14][15][16][17][18][19] Ethanol-induced apoptotic cell death has been well recognized in many cell types and animal models. [20][21][22][23][24] High concentrations of ethanol can effectively destroy hepatoma tumor as well as normal cells, whereas lower concentrations of ethanol selectively induces apoptosis in hepatoma tumor cells but not in normal hepatocytes.…”

Polymeric Micelles: Nanocarriers for Cancer-Targeted Drug Delivery

“…It was reported that curcumin blocks NF-κB pathway (107) and in turn, induces apoptosis and inhibits the function of protein kinase C, epidermal growth factor receptor tyrosine kinase, and HER-2 (108,109). Curcumin has shown antitumor activity against various types of cancers including those of breast (110), colon (111), prostate (112,113), kidney (114), liver (115), lymphoid and myeloid tissues (116), and melanoma (117). In spite of all the anticancer activities, the potential application of curcumin is hindered by its poor water solubility and limited bioavailability.…”