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Chemical composition and pharmacological bio-efficacy of Parrotiopsis jacquemontiana (Decne) Rehder for anticancer activity

Consistent STAT3 (Single transducer and activator of transcription 3) activation is observed in many tumors and promotes malignant cell transformation. In the present investigation, we evaluated the anticancer effects of Parrotiopsis jacquemontiana methanol fraction (PJM) on STAT3 inhibition in HCCL...

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Autores principales: Ali, Saima, Khan, Muhammad Rashid, Iqbal, Javed, Batool, Riffat, Naz, Irum, Yaseen, Tabassum, Abbasi, Banzeer Ahsan, Nasir, Jamal Abdul, El-Serehy, Hamed A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381063/
https://www.ncbi.nlm.nih.gov/pubmed/34466072
http://dx.doi.org/10.1016/j.sjbs.2021.07.072
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author Ali, Saima
Khan, Muhammad Rashid
Iqbal, Javed
Batool, Riffat
Naz, Irum
Yaseen, Tabassum
Abbasi, Banzeer Ahsan
Nasir, Jamal Abdul
El-Serehy, Hamed A.
author_facet Ali, Saima
Khan, Muhammad Rashid
Iqbal, Javed
Batool, Riffat
Naz, Irum
Yaseen, Tabassum
Abbasi, Banzeer Ahsan
Nasir, Jamal Abdul
El-Serehy, Hamed A.
author_sort Ali, Saima
collection PubMed
description Consistent STAT3 (Single transducer and activator of transcription 3) activation is observed in many tumors and promotes malignant cell transformation. In the present investigation, we evaluated the anticancer effects of Parrotiopsis jacquemontiana methanol fraction (PJM) on STAT3 inhibition in HCCLM3 and MDA-MB 231 cells. PJM suppressed the activation of upstream kinases i.e. JAK-1/2 (Janus kinase-1/2), and c-Src (Proto-oncogene tyrosine-protein kinase c-Src), and upregulated the expression levels of PIAS-1/3 (Protein Inhibitor of Activated STATs-1/3), SHP-1/2 (Src-homology region 2 domain-containing phosphatase-1/2), and PTP-1β (Protein tyrosine phosphatase 1 β) which negatively regulate STAT3 signaling pathway. PJM also decreased the levels of protein products conferring to various oncogenes, which in turn repressed the proliferation, migration, invasion, and induced apoptosis in cancer cell lines. The growth inhibitory effects of PJM on cell-cycle and metastasis were correlated with decreased expression levels of CyclinD1, CyclinE, MMP-2 (Matrix metalloproteinases-2), and MMP-9 (Matrix metalloproteinases-9). Induction of apoptosis was indicated by the cleavage and subsequent activation of Caspases (Cysteine-dependent Aspartate-directed Proteases) i.e. caspase-3, 7, 8, 9, and PARP (Poly (ADP-ribose) polymerase) as well as through the down-regulation of anti-apoptotic proteins. These apoptotic effects of PJM were preceded by inhibition of STAT3 cell-signaling pathway. STAT3 was needed for PJM-induced apoptosis, and inhibition of STAT3 via pharmacological inhibitor (Stattic; SC-203282) abolished the apoptotic effects. Conclusively, our results demonstrate the capability of PJM to inhibit cancer cell-proliferation and induce apoptosis by suppressing STAT3 via upregulation of STAT3 inhibitors and pro-apoptotic proteins whereas the down-regulation of upstream kinases and anti-apoptotic protein expression. In future, one-step advance studies of PHM regarding its role in metastatic inhibition, immune response modulation for reducing tumor, and inducing apoptosis in suitable animal models would be an interesting and promising research area.
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spelling pubmed-83810632021-08-30 Chemical composition and pharmacological bio-efficacy of Parrotiopsis jacquemontiana (Decne) Rehder for anticancer activity Ali, Saima Khan, Muhammad Rashid Iqbal, Javed Batool, Riffat Naz, Irum Yaseen, Tabassum Abbasi, Banzeer Ahsan Nasir, Jamal Abdul El-Serehy, Hamed A. Saudi J Biol Sci Original Article Consistent STAT3 (Single transducer and activator of transcription 3) activation is observed in many tumors and promotes malignant cell transformation. In the present investigation, we evaluated the anticancer effects of Parrotiopsis jacquemontiana methanol fraction (PJM) on STAT3 inhibition in HCCLM3 and MDA-MB 231 cells. PJM suppressed the activation of upstream kinases i.e. JAK-1/2 (Janus kinase-1/2), and c-Src (Proto-oncogene tyrosine-protein kinase c-Src), and upregulated the expression levels of PIAS-1/3 (Protein Inhibitor of Activated STATs-1/3), SHP-1/2 (Src-homology region 2 domain-containing phosphatase-1/2), and PTP-1β (Protein tyrosine phosphatase 1 β) which negatively regulate STAT3 signaling pathway. PJM also decreased the levels of protein products conferring to various oncogenes, which in turn repressed the proliferation, migration, invasion, and induced apoptosis in cancer cell lines. The growth inhibitory effects of PJM on cell-cycle and metastasis were correlated with decreased expression levels of CyclinD1, CyclinE, MMP-2 (Matrix metalloproteinases-2), and MMP-9 (Matrix metalloproteinases-9). Induction of apoptosis was indicated by the cleavage and subsequent activation of Caspases (Cysteine-dependent Aspartate-directed Proteases) i.e. caspase-3, 7, 8, 9, and PARP (Poly (ADP-ribose) polymerase) as well as through the down-regulation of anti-apoptotic proteins. These apoptotic effects of PJM were preceded by inhibition of STAT3 cell-signaling pathway. STAT3 was needed for PJM-induced apoptosis, and inhibition of STAT3 via pharmacological inhibitor (Stattic; SC-203282) abolished the apoptotic effects. Conclusively, our results demonstrate the capability of PJM to inhibit cancer cell-proliferation and induce apoptosis by suppressing STAT3 via upregulation of STAT3 inhibitors and pro-apoptotic proteins whereas the down-regulation of upstream kinases and anti-apoptotic protein expression. In future, one-step advance studies of PHM regarding its role in metastatic inhibition, immune response modulation for reducing tumor, and inducing apoptosis in suitable animal models would be an interesting and promising research area. Elsevier 2021-09 2021-08-02 /pmc/articles/PMC8381063/ /pubmed/34466072 http://dx.doi.org/10.1016/j.sjbs.2021.07.072 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Ali, Saima
Khan, Muhammad Rashid
Iqbal, Javed
Batool, Riffat
Naz, Irum
Yaseen, Tabassum
Abbasi, Banzeer Ahsan
Nasir, Jamal Abdul
El-Serehy, Hamed A.
Chemical composition and pharmacological bio-efficacy of Parrotiopsis jacquemontiana (Decne) Rehder for anticancer activity
title Chemical composition and pharmacological bio-efficacy of Parrotiopsis jacquemontiana (Decne) Rehder for anticancer activity
title_full Chemical composition and pharmacological bio-efficacy of Parrotiopsis jacquemontiana (Decne) Rehder for anticancer activity
title_fullStr Chemical composition and pharmacological bio-efficacy of Parrotiopsis jacquemontiana (Decne) Rehder for anticancer activity
title_full_unstemmed Chemical composition and pharmacological bio-efficacy of Parrotiopsis jacquemontiana (Decne) Rehder for anticancer activity
title_short Chemical composition and pharmacological bio-efficacy of Parrotiopsis jacquemontiana (Decne) Rehder for anticancer activity
title_sort chemical composition and pharmacological bio-efficacy of parrotiopsis jacquemontiana (decne) rehder for anticancer activity
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381063/
https://www.ncbi.nlm.nih.gov/pubmed/34466072
http://dx.doi.org/10.1016/j.sjbs.2021.07.072
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