Molecular targeting of Bcl-2 overcomes prostate cancer cell adaptation to XIAP gene downregulation

Nakano, Yuko; Bilim, Vladimir; Yuuki, Kaori; Muto, Andrea; Kato, Tomoyuki; Nagaoka, Akira; Tomita, Yoshihiko

doi:10.1038/pcan.2008.27

Cited by 4 publications

(3 citation statements)

References 23 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HDAC1 plays a critical role in the transition of prostate cancer cells from androgen dependence to androgen independence [49]. Studies have shown that treatment of prostate cancer cells with HDAC inhibitors results in XIAP inhibition and increased apoptosis [42]. Our studies demonstrate that apigenin treatment of prostate cancer cells causes a rapid decrease in HDAC1 and loss of HDAC1 recruitment leads to histone deacetylation at the XIAP promoter.…”

Section: Discussionmentioning

confidence: 56%

“…Transient transfection of prostate cancer cells with XIAP targeting siRNA produced a prominent downregulation of XIAP that resulted in apoptosis and significantly increased sensitivity to chemotherapeutic drugs [42]. Higher XIAP expression has been demonstrated in high-grade PIN lesions, and its aberrant expression correlates with prostate cancer progression and poor prognosis [12].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70–Bax interaction in prostate cancer

Shukla

Gupta

2014

Apoptosis

View full text Add to dashboard Cite

Dysfunction of the apoptotic pathway in prostate cancer cells confers apoptosis resistance towards various therapies. A novel strategy to overcome resistance is to directly target the apoptotic pathway in cancer cells. Apigenin, an anticancer agent, selectively toxic to cancer cells induces cell cycle arrest and apoptosis through mechanisms which are not fully explored. In the present study we provide novel insight into the mechanisms of apoptosis induction by apigenin. Treatment of androgen-refractory human prostate cancer PC-3 and DU145 cells with apigenin resulted in dose-dependent suppression of XIAP, c-IAP1, c-IAP2 and survivin protein levels. Apigenin treatment resulted in significant decrease in cell viability and apoptosis induction with the increase of cytochrome C in time-dependent manner. These effects of apigenin were accompanied by decrease in Bcl-xL and Bcl-2 and increase in the active form of Bax protein. The apigenin-mediated increase in Bax was due to dissociation of Bax from Ku70 which is essential for apoptotic activity of Bax. Apigenin treatment resulted in the inhibition of class I histone deacetylases and HDAC1 protein expression, thereby increasing the acetylation of Ku70 and the dissociation of Bax resulting in apoptosis of cancer cells. Furthermore, apigenin significantly reduced HDAC1 occupancy at the XIAP promoter, suggesting that histone deacetylation might be critical for XIAP downregulation. These results suggest that apigenin targets inhibitor of apoptosis proteins and Ku70–Bax interaction in the induction of apoptosis in prostate cancer cells and in athymic nude mouse xenograft model endorsing its in vivo efficacy.

show abstract

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70–Bax interaction in prostate cancer

Shukla

Gupta

2014

Apoptosis

View full text Add to dashboard Cite

show abstract

“…Due to the role of XIAP in preventing cell death, overexpression of XIAP can enhance cell tolerance to external and internal apoptotic stimuli [37], and dysregulation of XIAP has been shown to contribute toward the progression of multiple cancers, including bladder [38][39][40], breast [41][42][43], ovarian [44][45][46], lung [47][48][49], colon [50][51][52], and prostate [53][54][55][56]. Therefore, the expression profile of XIAP is thought to be part of a system of regulatory loops that balance a cell's response to environmental stimuli [37,57].…”

Section: Introductionmentioning

confidence: 99%

Lentiviral Gene Transfer Corrects Immune Abnormalities in XIAP Deficiency

et al. 2022

View full text Add to dashboard Cite

Background X-linked inhibitor of apoptosis protein (XIAP) deficiency is a severe immunodeficiency with clinical features including hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD) due to defective NOD2 responses. Management includes immunomodulatory therapies and hematopoietic stem cell transplant (HSCT). However, this cohort is particularly susceptible to the chemotherapeutic regimens and acutely affected by graft-vs-host disease (GvHD), driving poor long-term survival in transplanted patients. Autologous HSC gene therapy could offer an alternative treatment option and would abrogate the risks of alloreactivity. Methods Hematopoietic progenitor (Lin−ve) cells from XIAPy/− mice were transduced with a lentiviral vector encoding human XIAP cDNA before transplantation into irradiated XIAP y/− recipients. After 12 weeks animals were challenged with the dectin-1 ligand curdlan and recovery of innate immune function was evaluated though analysis of inflammatory cytokines, body weight, and splenomegaly. XIAP patient-derived CD14+ monocytes were transduced with the same vector and functional recovery was demonstrated using in vitro L18-MDP/NOD2 assays. Results In treated XIAPy/− mice, ~40% engraftment of gene-corrected Lin−ve cells led to significant recovery of weight loss, splenomegaly, and inflammatory cytokine responses to curdlan, comparable to wild-type mice. Serum IL-6, IL-10, MCP-1, and TNF were significantly reduced 2-h post-curdlan administration in non-corrected XIAPy/− mice compared to wild-type and gene-corrected animals. Appropriate reduction of inflammatory responses was observed in gene-corrected mice, whereas non-corrected mice developed an inflammatory profile 9 days post-curdlan challenge. In gene-corrected patient CD14+ monocytes, TNF responses were restored following NOD2 activation with L18-MDP. Conclusion Gene correction of HSCs recovers XIAP-dependent immune defects and could offer a treatment option for patients with XIAP deficiency.

show abstract

Co-expression of XIAP and CIAP1 Play Synergistic Effect on Patient’s Prognosis in Head and Neck Cancer

Yang

Liu

et al. 2018

Pathol. Oncol. Res.

View full text Add to dashboard Cite

Molecular targeting of Bcl-2 overcomes prostate cancer cell adaptation to XIAP gene downregulation

Cited by 4 publications

References 23 publications

Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70–Bax interaction in prostate cancer

Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70–Bax interaction in prostate cancer

Lentiviral Gene Transfer Corrects Immune Abnormalities in XIAP Deficiency

Co-expression of XIAP and CIAP1 Play Synergistic Effect on Patient’s Prognosis in Head and Neck Cancer

Contact Info

Product

Resources

About