Phytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins

Abstract Ajwa dates (Phoenix dactylifera L.) have been described in traditional and alternative medicine to provide several health benefits, but their mechanism of apoptosis induction against human triple-negative breast cancer MDA-MB-231 cells remains to be investigated. In this study, we analyzed...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mohsin Ali Khan, Sahabjada Siddiqui, Imran Ahmad, Romila Singh, Durga Prasad Mishra, Anand Narain Srivastava, Rumana Ahmad
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8cce6974fa084757a123c85e0b1d9fbd
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8cce6974fa084757a123c85e0b1d9fbd
record_format	dspace
spelling	oai:doaj.org-article:8cce6974fa084757a123c85e0b1d9fbd2021-12-02T16:50:31ZPhytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins10.1038/s41598-021-89420-z2045-2322https://doaj.org/article/8cce6974fa084757a123c85e0b1d9fbd2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89420-zhttps://doaj.org/toc/2045-2322Abstract Ajwa dates (Phoenix dactylifera L.) have been described in traditional and alternative medicine to provide several health benefits, but their mechanism of apoptosis induction against human triple-negative breast cancer MDA-MB-231 cells remains to be investigated. In this study, we analyzed the phytoconstituents in ethanolic Ajwa Dates Pulp Extract (ADPE) by liquid chromatography-mass spectrometry (LC–MS) and investigated anticancer effects against MDA-MB-231 cells. LC–MS analysis revealed that ADPE contained phytocomponents belonging to classes such as carbohydrates, phenolics, flavonoids and terpenoids. MTT assay demonstrated statistically significant dose- and time-dependent inhibition of MDA-MB-231 cells with IC50 values of 17.45 and 16.67 mg/mL at 24 and 48 h, respectively. Hoechst 33342 dye and DNA fragmentation data showed apoptotic cell death while AO/PI and Annexin V-FITC data revealed cells in late apoptosis at higher doses of ADPE. More importantly, ADPE prompted reactive oxygen species (ROS) induced alterations in mitochondrial membrane potential (MMP) in ADPE treated MDA-MB-231 cells. Cell cycle analysis demonstrated that ADPE induced cell arrest in S and G2/M checkpoints. ADPE upregulated the p53, Bax and cleaved caspase-3, thereby leading to the downregulation of Bcl-2 and AKT/mTOR pathway. ADPE did not show any significant toxicity on normal human peripheral blood mononuclear cells which suggests its safe application to biological systems under study. Thus, ADPE has the potential to be used as an adjunct to the mainline of treatment against breast cancer.Mohsin Ali KhanSahabjada SiddiquiImran AhmadRomila SinghDurga Prasad MishraAnand Narain SrivastavaRumana AhmadNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mohsin Ali Khan Sahabjada Siddiqui Imran Ahmad Romila Singh Durga Prasad Mishra Anand Narain Srivastava Rumana Ahmad Phytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins
description	Abstract Ajwa dates (Phoenix dactylifera L.) have been described in traditional and alternative medicine to provide several health benefits, but their mechanism of apoptosis induction against human triple-negative breast cancer MDA-MB-231 cells remains to be investigated. In this study, we analyzed the phytoconstituents in ethanolic Ajwa Dates Pulp Extract (ADPE) by liquid chromatography-mass spectrometry (LC–MS) and investigated anticancer effects against MDA-MB-231 cells. LC–MS analysis revealed that ADPE contained phytocomponents belonging to classes such as carbohydrates, phenolics, flavonoids and terpenoids. MTT assay demonstrated statistically significant dose- and time-dependent inhibition of MDA-MB-231 cells with IC50 values of 17.45 and 16.67 mg/mL at 24 and 48 h, respectively. Hoechst 33342 dye and DNA fragmentation data showed apoptotic cell death while AO/PI and Annexin V-FITC data revealed cells in late apoptosis at higher doses of ADPE. More importantly, ADPE prompted reactive oxygen species (ROS) induced alterations in mitochondrial membrane potential (MMP) in ADPE treated MDA-MB-231 cells. Cell cycle analysis demonstrated that ADPE induced cell arrest in S and G2/M checkpoints. ADPE upregulated the p53, Bax and cleaved caspase-3, thereby leading to the downregulation of Bcl-2 and AKT/mTOR pathway. ADPE did not show any significant toxicity on normal human peripheral blood mononuclear cells which suggests its safe application to biological systems under study. Thus, ADPE has the potential to be used as an adjunct to the mainline of treatment against breast cancer.
format	article
author	Mohsin Ali Khan Sahabjada Siddiqui Imran Ahmad Romila Singh Durga Prasad Mishra Anand Narain Srivastava Rumana Ahmad
author_facet	Mohsin Ali Khan Sahabjada Siddiqui Imran Ahmad Romila Singh Durga Prasad Mishra Anand Narain Srivastava Rumana Ahmad
author_sort	Mohsin Ali Khan
title	Phytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins
title_short	Phytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins
title_full	Phytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins
title_fullStr	Phytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins
title_full_unstemmed	Phytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins
title_sort	phytochemicals from ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting akt/mtor pathway and modulating bcl-2 family proteins
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8cce6974fa084757a123c85e0b1d9fbd
work_keys_str_mv	AT mohsinalikhan phytochemicalsfromajwadatespulpextractinduceapoptosisinhumantriplenegativebreastcancerbyinhibitingaktmtorpathwayandmodulatingbcl2familyproteins AT sahabjadasiddiqui phytochemicalsfromajwadatespulpextractinduceapoptosisinhumantriplenegativebreastcancerbyinhibitingaktmtorpathwayandmodulatingbcl2familyproteins AT imranahmad phytochemicalsfromajwadatespulpextractinduceapoptosisinhumantriplenegativebreastcancerbyinhibitingaktmtorpathwayandmodulatingbcl2familyproteins AT romilasingh phytochemicalsfromajwadatespulpextractinduceapoptosisinhumantriplenegativebreastcancerbyinhibitingaktmtorpathwayandmodulatingbcl2familyproteins AT durgaprasadmishra phytochemicalsfromajwadatespulpextractinduceapoptosisinhumantriplenegativebreastcancerbyinhibitingaktmtorpathwayandmodulatingbcl2familyproteins AT anandnarainsrivastava phytochemicalsfromajwadatespulpextractinduceapoptosisinhumantriplenegativebreastcancerbyinhibitingaktmtorpathwayandmodulatingbcl2familyproteins AT rumanaahmad phytochemicalsfromajwadatespulpextractinduceapoptosisinhumantriplenegativebreastcancerbyinhibitingaktmtorpathwayandmodulatingbcl2familyproteins
_version_	1718383051336056832

Phytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins

Ejemplares similares