bafilomycin-a1 and Prostatic-Neoplasms

bafilomycin-a1 has been researched along with Prostatic-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for bafilomycin-a1 and Prostatic-Neoplasms

Article	Year
Excess hepsin proteolytic activity limits oncogenic signaling and induces ER stress and autophagy in prostate cancer cells. Cell death & disease, 2019, 08-09, Volume: 10, Issue:8 Topics: Animals; Autophagy; Carcinogenesis; Cinnamates; Endoplasmic Reticulum Stress; Endoplasmic Reticulum-Associated Degradation; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Macrolides; Male; Mice; Microtubule-Associated Proteins; Neoplastic Stem Cells; PC-3 Cells; Prostatic Neoplasms; Sequestosome-1 Protein; Serine Endopeptidases; Thiourea	2019
Dual inhibition of autophagy and the AKT pathway in prostate cancer. Autophagy, 2013, Volume: 9, Issue:7 Genetic inactivation of PTEN through either gene deletion or mutation is common in metastatic prostate cancer, leading to activation of the phosphoinositide 3-kinase (PI3K-AKT) pathway, which is associated with poor clinical outcomes. The PI3K-AKT pathway plays a central role in various cellular processes supporting cell growth and survival of tumor cells. To date, therapeutic approaches to develop inhibitors targeting the PI3K-AKT pathway have failed in both pre-clinical and clinical trials. We showed that a novel AKT inhibitor, AZD5363, inhibits the AKT downstream pathway by reducing p-MTOR and p-RPS6KB/p70S6K. We specifically reported that AZD5363 monotherapy induces G2 growth arrest and autophagy, but fails to induce significant apoptosis in PC-3 and DU145 prostate cancer cell lines. Blocking autophagy using pharmacological inhibitors (3-methyladenine, chloroquine and bafilomycin A 1) or genetic inhibitors (siRNA targeting ATG3 and ATG7) enhances cell death induced by AZD5363 in these prostate cancer cells. Importantly, the combination of AZD5363 with chloroquine significantly reduces tumor volume compared with the control group, and compared with either drug alone in prostate tumor xenograft models. Taken together, these data demonstrate that AKT inhibitor AZD5363, synergizes with the lysosomotropic inhibitor of autophagy, chloroquine, to induce apoptosis and delay tumor progression in prostate cancer models that are resistant to monotherapy, with AZD5363 providing a new therapeutic approach potentially translatable to patients. Topics: Adenine; Autophagy; Cell Line, Tumor; Chloroquine; Clinical Trials, Phase I as Topic; Humans; Macrolides; Male; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Pyrimidines; Pyrroles; Signal Transduction	2013

Article

Year

Excess hepsin proteolytic activity limits oncogenic signaling and induces ER stress and autophagy in prostate cancer cells.

Cell death & disease, 2019, 08-09, Volume: 10, Issue:8

Topics: Animals; Autophagy; Carcinogenesis; Cinnamates; Endoplasmic Reticulum Stress; Endoplasmic Reticulum-Associated Degradation; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Macrolides; Male; Mice; Microtubule-Associated Proteins; Neoplastic Stem Cells; PC-3 Cells; Prostatic Neoplasms; Sequestosome-1 Protein; Serine Endopeptidases; Thiourea

2019

Dual inhibition of autophagy and the AKT pathway in prostate cancer.

Autophagy, 2013, Volume: 9, Issue:7

Genetic inactivation of PTEN through either gene deletion or mutation is common in metastatic prostate cancer, leading to activation of the phosphoinositide 3-kinase (PI3K-AKT) pathway, which is associated with poor clinical outcomes. The PI3K-AKT pathway plays a central role in various cellular processes supporting cell growth and survival of tumor cells. To date, therapeutic approaches to develop inhibitors targeting the PI3K-AKT pathway have failed in both pre-clinical and clinical trials. We showed that a novel AKT inhibitor, AZD5363, inhibits the AKT downstream pathway by reducing p-MTOR and p-RPS6KB/p70S6K. We specifically reported that AZD5363 monotherapy induces G2 growth arrest and autophagy, but fails to induce significant apoptosis in PC-3 and DU145 prostate cancer cell lines. Blocking autophagy using pharmacological inhibitors (3-methyladenine, chloroquine and bafilomycin A 1) or genetic inhibitors (siRNA targeting ATG3 and ATG7) enhances cell death induced by AZD5363 in these prostate cancer cells. Importantly, the combination of AZD5363 with chloroquine significantly reduces tumor volume compared with the control group, and compared with either drug alone in prostate tumor xenograft models. Taken together, these data demonstrate that AKT inhibitor AZD5363, synergizes with the lysosomotropic inhibitor of autophagy, chloroquine, to induce apoptosis and delay tumor progression in prostate cancer models that are resistant to monotherapy, with AZD5363 providing a new therapeutic approach potentially translatable to patients.

Topics: Adenine; Autophagy; Cell Line, Tumor; Chloroquine; Clinical Trials, Phase I as Topic; Humans; Macrolides; Male; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Pyrimidines; Pyrroles; Signal Transduction

2013