Acetyl-Keto-β-Boswellic Acid Induces Apoptosis through a Death Receptor 5–Mediated Pathway in Prostate Cancer Cells

Lü, Min; Xia, Lijuan; Hua, Hui‐Ming; Jing, Yongkui

doi:10.1158/0008-5472.can-07-2978

Cited by 110 publications

(79 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We found that gossypol induced CHOP and that the gene silencing of CHOP by siRNA blocked the effect of gossypol on the induction of death receptors and on TRAILinduced apoptosis. Our findings are similar to those of other studies that indicated that CHOP binds to the DR5 promoter and up-regulates this receptor expression (29,42,43). Although p53 induction has also been linked to DR5 induction (27), we found that gossypol-induced up-regulation of TRAIL receptor DR5 was independent of p53.…”

Section: Discussionsupporting

confidence: 92%

Gossypol Induces Death Receptor-5 through Activation of the ROS-ERK-CHOP Pathway and Sensitizes Colon Cancer Cells to TRAIL

Sung¹,

Ravindran²,

Prasad

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Development of resistance to TRAIL, an apoptosis-inducing cytokine, is one of the major problems in its development for cancer treatment. Thus, pharmacological agents that are safe and can sensitize the tumor cells to TRAIL are urgently needed. We investigated whether gossypol, a BH3 mimetic that is currently in the clinic, can potentiate TRAIL-induced apoptosis. Intracellular esterase activity, sub-G 1 cell cycle arrest, and caspase-8, -9, and -3 activity assays revealed that gossypol potentiated TRAIL-induced apoptosis in human colon cancer cells. Gossypol also down-regulated cell survival proteins (Bclx L , Bcl-2, survivin, XIAP, and cFLIP) and dramatically up-regulated TRAIL death receptor (DR)-5 expression but had no effect on DR4 and decoy receptors. Gossypol-induced receptor induction was not cell type-specific, as DR5 induction was observed in other cell types. Deletion of DR5 by siRNA significantly reduced the apoptosis induced by TRAIL and gossypol. Gossypol induction of the death receptor required the induction of CHOP, and thus, gene silencing of CHOP abolished gossypol-induced DR5 expression and associated potentiation of apoptosis. ERK1/2 (but not p38 MAPK or JNK) activation was also required for gossypol-induced TRAIL receptor induction; gene silencing of ERK abolished both DR5 induction and potentiation of apoptosis by TRAIL. We also found that reactive oxygen species produced by gossypol treatment was critical for TRAIL receptor induction and apoptosis potentiation. Overall, our results show that gossypol enhances TRAIL-induced apoptosis through the down-regulation of cell survival proteins and the up-regulation of TRAIL death receptors through the ROS-ERK-CHOP-DR5 pathway.

show abstract

Section: Discussionsupporting

confidence: 92%

Gossypol Induces Death Receptor-5 through Activation of the ROS-ERK-CHOP Pathway and Sensitizes Colon Cancer Cells to TRAIL

Sung¹,

Ravindran²,

Prasad

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…4D). Consistent with our findings, MG132 (proteasome inhibitor) and triterpenoid also induced DR5 up-regulation through CHOP protein [40,41].…”

Section: Discussionsupporting

confidence: 92%

Acrolein sensitizes human renal cancer Caki cells to TRAIL-induced apoptosis via ROS-mediated up-regulation of death receptor-5 (DR5) and down-regulation of Bcl-2

Yang

Woo

Choi

et al. 2011

Experimental Cell Research

View full text Add to dashboard Cite

“…Furthermore, we found a strong upregulation of the bZIP transcription factor DDIT3 -notably independent of p53 -after PDT. Since DDIT3 had been implicated in anti-proliferative effects and the induction of apoptosis by certain anticancer agents, including in PC-3 cells [58], the observed high levels may have also contributed to growth arrest and apoptotic signaling in our experiment after PDT.…”

Section: Discussionmentioning

confidence: 85%

Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro

Gyenge

Hiestand

Graefe

et al. 2011

Photodiagnosis and Photodynamic Therapy

View full text Add to dashboard Cite

BACKGROUND: Meso-tetra-hydroxyphenyl-chlorine (mTHPC) is among the most powerful photosensitizers available for photodynamic therapy (PDT). However, the mechanisms leading to cell death are poorly understood. We here focused on changes at DNA and RNA levels after treatment with the liposomal mTHPC derivative Foslipos in vitro. METHODS: After determination of darktoxicity, laser conditions and uptake kinetics, PC-3 prostate carcinoma cells were subjected to PDT with Foslipos, followed by assessment of cell numbers directly (TP0) or 1h (TP1), 2h (TP2), 5h (TP5) and 24h (TP24) after illumination. Nucleic acids had been extracted for evaluation of RNA amounts and integrity as well as for estimation of abasic sites as a measure for DNA damage. Furthermore, expression changes of 84 genes related to oxidative stress were investigated by quantitative polymerase chain reaction. RESULTS: Already at TP0, the number of dead cells was significantly higher after PDT versus controls and at TP24 more than 90% of cells had been destroyed. PDT resulted in a severe damage of both RNA and DNA. Gene expression analyses revealed an impact of PDT on pathways for oxidative and metabolic stress, heat shock, proliferation and carcinogenesis, growth arrest, inflammation, DNA repair and apoptosis signaling. CONCLUSIONS: Mechanisms of Foslipos-mediated PDT comprise a combination of acute and delayed lethal effects in PC-3 cells. The latter may include death processes initiated by nucleic acid damage, activation of stress and growth arrest genes in combination with a reduced capability to adequately cope with oxidative toxicity. Our results will help to better understand molecular photodynamic effects. AbstractBackground: Meso-tetra-hydroxyphenyl-chlorine (mTHPC) is among the most powerful

show abstract

Acetyl-Keto-β-Boswellic Acid Induces Apoptosis through a Death Receptor 5–Mediated Pathway in Prostate Cancer Cells

Cited by 110 publications

References 46 publications

Gossypol Induces Death Receptor-5 through Activation of the ROS-ERK-CHOP Pathway and Sensitizes Colon Cancer Cells to TRAIL

Gossypol Induces Death Receptor-5 through Activation of the ROS-ERK-CHOP Pathway and Sensitizes Colon Cancer Cells to TRAIL

Acrolein sensitizes human renal cancer Caki cells to TRAIL-induced apoptosis via ROS-mediated up-regulation of death receptor-5 (DR5) and down-regulation of Bcl-2

Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro

Contact Info

Product

Resources

About