HIV‐1 protease inhibitor induces growth arrest and apoptosis of human prostate cancer LNCaP cells in vitro and in vivo in conjunction with blockade of androgen receptor STAT3 and AKT signaling

  title={HIV‐1 protease inhibitor induces growth arrest and apoptosis of human prostate cancer LNCaP cells in vitro and in vivo in conjunction with blockade of androgen receptor STAT3 and AKT signaling},
  author={Yang Yang and Takayuki Ikezoe and Tamotsu Takeuchi and Yoshihiro Adachi and Yuji Ohtsuki and Seisho Takeuchi and H. Phillip Koeffler and Hirokuni Taguchi},
  journal={Cancer Science},
This study found that the HIV‐1 protease inhibitor nelfinavir (NFV) induced growth arrest and apoptosis of human prostate cancer cells (LNCaP, DU145 and PC‐3 cells), as measured by MTT and terminal deoxyribonucleotide transferase‐mediated dUTP nick end labeling (TUNEL) assays, respectively, on the third day of culture. In addition, NFV blocked androgen receptor (AR) signaling in association with downregulation of nuclear levels of AR in LNCaP cells as measured by reporter assay and western blot… 

Human immunodeficiency virus protease inhibitors reduce the growth of human tumors via a proteasome‐independent block of angiogenesis and matrix metalloproteinases

Indinavir and saquinavir significantly inhibited the growth of all adenocarcinomas tested in the mice model, suggesting that HIV‐PIs or their analogues, characterized by a better biodistribution and lower toxicity, may represent a new class of antitumor drugs capable of targeting both matrix metalloproteinases and the proteasome for a most effective antitumors therapy.

Effect of SU11248 on gastrointestinal stromal tumor‐T1 cells: Enhancement of growth inhibition via inhibition of 3‐kinase/Akt/mammalian target of rapamycin signaling

Clinical studies of SU11248 for individuals with GIST are supported, and the combination of SU 11248 and inhibitors of 3‐kinase/Akt/mammalian target of rapamycin signaling represents a promising novel treatment strategy.

Nelfinavir inhibits regulated intramembrane proteolysis of sterol regulatory element binding protein‐1 and activating transcription factor 6 in castration‐resistant prostate cancer

S2P is validates S2P as a therapeutic target in castration‐resistant prostate cancer and provides new insights into nelfinavir‐induced endoplasmic reticulum stress and cancer cell death, and is proposed for investigating its clinical activity in castrated prostate cancer.

The human immunodeficiency virus-1 protease inhibitor nelfinavir impairs proteasome activity and inhibits the proliferation of multiple myeloma cells in vitro and in vivo

Nelfinavir enhanced the anti-proliferative activity of bortezomib, dexamethasone and histone deacetylase inhibitors and delayed tumor growth in a myeloma mouse model, suggesting that nelfinavIR, used at a pharmacological dosage, alone or in combination, may be useful in the treatment of Myeloma.

ZD6474 induces growth arrest and apoptosis of GIST‐T1 cells, which is enhanced by concomitant use of sunitinib

ZD6474 induced growth arrest and apoptosis of GIST‐T1 cells in association with blockade of c‐Kit and its downstream effectors, including Akt and extracellular signal‐regulated kinase (ERK).

Radiosensitization of Epidermal Growth Factor Receptor/HER2–Positive Pancreatic Cancer Is Mediated by Inhibition of Akt Independent of Ras Mutational Status

Inhibition of EGFR/HER2 enhances radiosensitivity in wild-type K-ras pancreatic cancer, and nelfinavir, and other phosphoinositide 3-kinase/Akt inhibitors, are effective pancreatic radiosensitizers regardless ofK-ras mutation status.

IL-6 and PPARγ Signalling in Human PC-3 Prostate Cancer Cells

The natural PPARγ ligand, 15deoxy Δ12-14 PGJ 2 (15dPGJ 2), and IL-6 were used to define their interactions on proliferation and signal transduction in PC-3 cells to study the effects of these ligands on prostate cancer cell proliferation and survival.



HIV-1 protease inhibitor induces growth arrest and apoptosis of human multiple myeloma cells via inactivation of signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2.

Protease inhibitors might be useful for treatment of individuals with multiple myeloma and inhibit production of vascular endothelial growth factor one of the targets of STAT 3, in U266 and RPMI8226 cells as measured by ELISA.

Proteasome inhibitor PS‐341 down‐regulates prostate‐specific antigen (PSA) and induces growth arrest and apoptosis of androgen‐dependent human prostate cancer LNCaP cells

The results indicate that PS‐341 induced growth arrest and apoptosis of LNCaP cells by blockade of the AR signaling pathway, indicating that the proteasome may be a molecular target for treatment of a variety of cancers including prostate cancer.

The human immunodeficiency virus (HIV)-1 protease inhibitor saquinavir inhibits proteasome function and causes apoptosis and radiosensitization in non-HIV-associated human cancer cells.

It is concluded that saquinavir inhibits proteasome activity in mammalian cells as well as acting on the HIV-I protease, which might become a new class of cytotoxic drugs, alone or in combination with radiation or chemotherapy.

HIV-1 Protease Inhibitor, Ritonavir

Combination therapy of ritonavir and anticancer drugs holds promise for the treatment of individuals with advanced, drug resistant cancers.

Regulation of TRAIL Expression by the Phosphatidylinositol 3-Kinase/Akt/GSK-3 Pathway in Human Colon Cancer Cells*

Results identify TRAIL, a novel TNF family member, as a downstream target of the PI 3-kinase/Akt/GSK-3 pathway and may have important implications for better understanding the role of thePI 3- Kinase pathway in intestinal cell homeostasis.

Antagonism between PTEN/MMAC1/TEP-1 and Androgen Receptor in Growth and Apoptosis of Prostatic Cancer Cells*

The data suggest that the loss of PTEN function may induce tumorigenesis through unopposed activity of the AR as well as contribute to the resistance of prostate cancers to androgen ablation therapy.

Signal transducer and activator of transcription 3 (STAT3) activation in prostate cancer: Direct STAT3 inhibition induces apoptosis in prostate cancer lines.

STAT3-specific inhibitors, rather than JAK kinase- specific inhibitors, should be more useful therapeutically in treating androgen-resistant prostate cancer and that STAT3 is an appropriate target in the treatment of prostate cancer are concluded.

Constitutive activation of Stat3 in human prostate tumors and cell lines: direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells.

It is demonstrated that constitutive activation of Stat3 occurs frequently in primary prostate adenocarcinomas and is critical for the growth and survival of prostate cancer cells.

Proliferation of adult T cell leukemia/lymphoma cells is associated with the constitutive activation of JAK/STAT proteins.

Results imply that JAK/STAT activation is associated with replication of leukemic cells and that therapeutic approaches aimed at JAK-STAT inhibition may be considered to halt neoplastic growth.

Inhibition of constitutive STAT3 activity sensitizes resistant non-Hodgkin's lymphoma and multiple myeloma to chemotherapeutic drug-mediated apoptosis.

  • S. AlasB. Bonavida
  • Biology
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2003
It is demonstrated by phosphoprotein immunoblotting analysis and electrophoretic mobility shift analysis that piceatannol and AG490 inhibit the constitutive activity of STAT3 in 2F7 and U266, respectively, and are a novel class of chemotherapeutic sensitizing agents capable of reversing the drug-resistant phenotype of cytokine-dependent tumor cells.