Tissue microarray profiling and integrative proteomics indicate the modulatory potential of Maytenus royleanus in inhibition of overexpressed TPD52 in prostate cancers

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 gene...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Maria Shabbir, Hasan Mukhtar, Deeba Syed, Suhail Razak, Tayyaba Afsar, Ali Almajwal, Yasmin Badshah, Dara Aldisi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/639e9430794c4f89963fe61905eee7f8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:639e9430794c4f89963fe61905eee7f8
record_format	dspace
spelling	oai:doaj.org-article:639e9430794c4f89963fe61905eee7f82021-12-02T17:52:13ZTissue microarray profiling and integrative proteomics indicate the modulatory potential of Maytenus royleanus in inhibition of overexpressed TPD52 in prostate cancers10.1038/s41598-021-91408-82045-2322https://doaj.org/article/639e9430794c4f89963fe61905eee7f82021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91408-8https://doaj.org/toc/2045-2322Abstract 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.Maria ShabbirHasan MukhtarDeeba SyedSuhail RazakTayyaba AfsarAli AlmajwalYasmin BadshahDara AldisiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-21 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria Shabbir Hasan Mukhtar Deeba Syed Suhail Razak Tayyaba Afsar Ali Almajwal Yasmin Badshah Dara Aldisi Tissue microarray profiling and integrative proteomics indicate the modulatory potential of Maytenus royleanus in inhibition of overexpressed TPD52 in prostate cancers
description	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.
format	article
author	Maria Shabbir Hasan Mukhtar Deeba Syed Suhail Razak Tayyaba Afsar Ali Almajwal Yasmin Badshah Dara Aldisi
author_facet	Maria Shabbir Hasan Mukhtar Deeba Syed Suhail Razak Tayyaba Afsar Ali Almajwal Yasmin Badshah Dara Aldisi
author_sort	Maria Shabbir
title	Tissue microarray profiling and integrative proteomics indicate the modulatory potential of Maytenus royleanus in inhibition of overexpressed TPD52 in prostate cancers
title_short	Tissue microarray profiling and integrative proteomics indicate the modulatory potential of Maytenus royleanus in inhibition of overexpressed TPD52 in prostate cancers
title_full	Tissue microarray profiling and integrative proteomics indicate the modulatory potential of Maytenus royleanus in inhibition of overexpressed TPD52 in prostate cancers
title_fullStr	Tissue microarray profiling and integrative proteomics indicate the modulatory potential of Maytenus royleanus in inhibition of overexpressed TPD52 in prostate cancers
title_full_unstemmed	Tissue microarray profiling and integrative proteomics indicate the modulatory potential of Maytenus royleanus in inhibition of overexpressed TPD52 in prostate cancers
title_sort	tissue microarray profiling and integrative proteomics indicate the modulatory potential of maytenus royleanus in inhibition of overexpressed tpd52 in prostate cancers
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/639e9430794c4f89963fe61905eee7f8
work_keys_str_mv	AT mariashabbir tissuemicroarrayprofilingandintegrativeproteomicsindicatethemodulatorypotentialofmaytenusroyleanusininhibitionofoverexpressedtpd52inprostatecancers AT hasanmukhtar tissuemicroarrayprofilingandintegrativeproteomicsindicatethemodulatorypotentialofmaytenusroyleanusininhibitionofoverexpressedtpd52inprostatecancers AT deebasyed tissuemicroarrayprofilingandintegrativeproteomicsindicatethemodulatorypotentialofmaytenusroyleanusininhibitionofoverexpressedtpd52inprostatecancers AT suhailrazak tissuemicroarrayprofilingandintegrativeproteomicsindicatethemodulatorypotentialofmaytenusroyleanusininhibitionofoverexpressedtpd52inprostatecancers AT tayyabaafsar tissuemicroarrayprofilingandintegrativeproteomicsindicatethemodulatorypotentialofmaytenusroyleanusininhibitionofoverexpressedtpd52inprostatecancers AT alialmajwal tissuemicroarrayprofilingandintegrativeproteomicsindicatethemodulatorypotentialofmaytenusroyleanusininhibitionofoverexpressedtpd52inprostatecancers AT yasminbadshah tissuemicroarrayprofilingandintegrativeproteomicsindicatethemodulatorypotentialofmaytenusroyleanusininhibitionofoverexpressedtpd52inprostatecancers AT daraaldisi tissuemicroarrayprofilingandintegrativeproteomicsindicatethemodulatorypotentialofmaytenusroyleanusininhibitionofoverexpressedtpd52inprostatecancers
_version_	1718379230087086080

Tissue microarray profiling and integrative proteomics indicate the modulatory potential of Maytenus royleanus in inhibition of overexpressed TPD52 in prostate cancers

Ejemplares similares