Dataset Information

Instructed-Assembly of Small Peptides Inhibits Drug-Resistant Prostate Cancer Cells.

ABSTRACT: Despite multiple new-drug approvals in recent years, prostate cancer remains a global health challenge because of the prostate cancers are resistant to androgen deprivation therapy. Here we show that a small D-phosphopeptide undergoes prostatic acid phosphatase (PAP)-instructed self-assembly for inhibiting castration-resistant prostate cancer (CRPC) cells. Specifically, the installation of phosphate at the C-terminal of a D-tripeptide results in the D-phosphopeptide. Dephosphorylating the D-phosphopeptide by PAP forms uniform nanofibers that inhibit VCaP, a castration-resistant prostate cancer cell. A non-hydrolyzable phosphate analogue of the D-phosphopeptide, which shares similar self-assembling properties with the D-phosphopeptide, confirms that PAP-instructed assembly is critical for the inhibition of VCaP. This work, for the first time, demonstrates PAP-instructed self-assembly of peptides for selective inhibiting castration-resistant prostate cancer (CRPC) cells.

SUBMITTER: Feng Z

PROVIDER: S-EPMC7043405 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Instructed-Assembly of Small Peptides Inhibits Drug-Resistant Prostate Cancer Cells.

Feng Zhaoqianqi Z Wang Huaimin H Yi Meihui M Lo Chieh-Yun CY Sallee Ashanti A Hsieh Jer-Tsong JT Xu Bing B

Peptide science (Hoboken, N.J.) 20190612 1

Despite multiple new-drug approvals in recent years, prostate cancer remains a global health challenge because of the prostate cancers are resistant to androgen deprivation therapy. Here we show that a small D-phosphopeptide undergoes prostatic acid phosphatase (PAP)-instructed self-assembly for inhibiting castration-resistant prostate cancer (CRPC) cells. Specifically, the installation of phosphate at the C-terminal of a D-tripeptide results in the D-phosphopeptide. Dephosphorylating the D-phos ...[more]

PMID: 32104754

Similar Datasets

Project description:BackgroundThe association of circulating lipids with clinical outcomes of drug-resistant castration-resistant prostate cancer (DR-CRPC) is not fully understood. While it is known that increases in select lipids correlate to decreased survival, neither the mechanisms mediating these alterations nor the correlation of resistance to drug treatments is well characterized.MethodsThis gap-in-knowledge was addressed using in vitro models of non-cancerous, hormone-sensitive, CRPC and drug-resistant cell lines combined with quantitative LC-ESI-Orbitrap-MS (LC-ESI-MS/MS) lipidomic analysis and subsequent analysis such as Metaboanalyst and Lipid Pathway Enrichment Analysis (LIPEA).ResultsSeveral lipid regulatory pathways were identified that are associated with Docetaxel resistance in prostate cancer (PCa). These included those controlling glycerophospholipid metabolism, sphingolipid signaling and ferroptosis. In total, 7460 features were identified as being dysregulated between the cell lines studied, and 21 lipid species were significantly altered in drug-resistant cell lines as compared to nonresistant cell lines. Docetaxel resistance cells (PC3-Rx and DU145-DR) had higher levels of phosphatidylcholine (PC), oxidized lipid species, phosphatidylethanolamine (PE), and sphingomyelin (SM) as compared to parent control cells (PC-3 and DU-145). Alterations were also identified in the levels of phosphatidic acid (PA) and diacylglyceride (DAG), whose levels are regulated by Lipin (LPIN), a phosphatidic acid phosphatase that converts PA to DAG. Data derived from cBioPortal demonstrated a population of PCa patients expressing mutations aligning with amplification of LPIN1, LPIN2 and LPIN3 genes. Lipin amplification in these genes correlated to decreased survival in these patients. Lipin-1 mRNA expression also showed a similar trend in PCa patient data. Lipin-1, but not Lipin-2 or - 3, was detected in several prostate cancer cells, and was increased in 22RV1 and PC-3 cell lines. The increased expression of Lipin-1 in these cells correlated with the level of PA.ConclusionThese data identify lipids whose levels may correlate to Docetaxel sensitivity and progression of PCa. The data also suggest a correlation between the expression of Lipin-1 in cells and patients with regards to prostate cancer cell aggressiveness and patient survivability. Ultimately, these data may be useful for identifying markers of lethal and/or metastatic prostate cancer.

Dataset Information

Instructed-Assembly of Small Peptides Inhibits Drug-Resistant Prostate Cancer Cells.

Publications

Instructed-Assembly of Small Peptides Inhibits Drug-Resistant Prostate Cancer Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets