Tissue microarray profiling and integrative proteomics indicate the modulatory potential of Maytenus royleanus in inhibition of overexpressed TPD52 in prostate ... View Full Text


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Article Info

DATE

2021-06-07

AUTHORS

Maria Shabbir, Hasan Mukhtar, Deeba Syed, Suhail Razak, Tayyaba Afsar, Ali Almajwal, Yasmin Badshah, Dara Aldisi

ABSTRACT

Maytenus roylanus (MEM) is a plant with anti-proliferative effects against prostate cancer. We aimed to explore the mechanism of action of MEM in prostate cancer (PCa) by employing an in vitro global proteome approach to get useful information of various signaling pathways and effected genes to define the mechanism of MEM action in prostate cancer. We conducted a global proteome analysis of CWR22Rv1after treatment with methanolic extract of MEM. The result of the proteomic profiling of in vitro PCa cells demonstrated the reduction in tumor protein D52 (TPD52) expression after treatment with methanolic extract of MEM. Down-regulation of TPD52 expression at mRNA level was observed by MEM treatment in CWR22Rν1 and C4-2 cells in a dose-dependent fashion probably by cleavage of Caspase 3 and PARP, or by modulation of cyclin-dependent kinases in CWR22Rν1 and C4-2 cells. The progressive character of the TRAMP model demonstrates a chance to evaluate the potential of chemo-preventive agents for both initial and late stages of prostate cancer development, and induction in TPD52 protein expression with development as well as the progression of prostate cancer was observed in the TRAMP model. Analyses of the tissue microarray collection of 25 specimens confirmed the clinical significance of our findings identifying TPD52 as a potential marker for PCa progression. We determined that knockdown of TPD52 (CWR22Rν1 cells), a considerable downregulation was seen at the protein level. Downregulation of TPD52 inhibited the migration and invasive behavior of prostate cancer cells as observed. Moreover, we observed that the siRNA-TPD52 transfection of CWR22Rν1 cells resulted in tumor growth inhibition with a marked reduction in the secretion of prostate-specific antigen (PSA) in the serum. Intraperitoneal injection of MEM considerably slowed tumor growth in athymic mice, inhibited TPD52 expression, and caused a marked reduction in PSA levels of serum as demonstrated by immunoblot screening and immune-histochemical staining. This report illustrates a molecular overview of pathological processes in PCa, indicating possible new disease biomarkers and therapeutic targets. More... »

PAGES

11935

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-021-91408-8

DOI

http://dx.doi.org/10.1038/s41598-021-91408-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1138658766

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34099820


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133 serum
134 signaling pathways
135 significance
136 specimens
137 stage
138 staining
139 target
140 therapeutic target
141 tissue
142 tissue microarray profiling
143 transfection
144 treatment
145 tumor growth
146 tumor growth inhibition
147 useful information
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