Chimaphila umbellata extract exerts anti-proliferative effect on human breast cancer cells via RIP1K/RIP3K-mediated necroptosis

Background: Chimaphila umbellata (CU) is a small perennial plant whose roots and leaves are used in the preparation of homeopathic medicines. In this study, the anti-proliferative and apoptotic effects of CU extract, obtained from its homeopathic mother tincture, were evaluated in human breast cance...

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Autores principales:	Neeladrisingha Das, Subhashish Samantaray, Chandrachur Ghosh, Komal Kushwaha, Debabrata Sircar, Partha Roy
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Cimaphila umbellata MCF-7 cells Anti-angiogenesis Anti-cancer Clonogenic assay Other systems of medicine RZ201-999
Acceso en línea:	https://doaj.org/article/04ce1685dc01485ab59c25c502d2e33a
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spelling	oai:doaj.org-article:04ce1685dc01485ab59c25c502d2e33a2021-11-26T04:42:37ZChimaphila umbellata extract exerts anti-proliferative effect on human breast cancer cells via RIP1K/RIP3K-mediated necroptosis2667-031310.1016/j.phyplu.2021.100159https://doaj.org/article/04ce1685dc01485ab59c25c502d2e33a2022-02-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S266703132100141Xhttps://doaj.org/toc/2667-0313Background: Chimaphila umbellata (CU) is a small perennial plant whose roots and leaves are used in the preparation of homeopathic medicines. In this study, the anti-proliferative and apoptotic effects of CU extract, obtained from its homeopathic mother tincture, were evaluated in human breast cancer cell lines. Methods: MTT assay was used to evaluate the dose- and time-dependent cytotoxicity of the extract in MCF-7 and HEK293 cells. The anti-proliferative effect of the extract was evaluated using the clonogenic and wound healing assays. The anti-angiogenic activity of the drug was evaluated using the chick chorioallantoic membrane assay. The mode of cell death was analyzed using Annexin V and PI staining assays through flow cytometry. In addition, the expression patterns of associated genes were evaluated using immunoblot analysis. Results: CU extracts exerted anti-proliferative effect in breast cancer cell line, i.e., MCF-7 cells, by inhibiting their growth and migration. The extract also demonstrated significant anti-angiogenic ability, limiting the de-novo blood vessel growth and development in chick embryos. The extract was found to increase caspase-independent necroptosis by involving RIP1/RIP3 kinases and MLKL proteins. This finding was further confirmed by using NEC-1 (an inhibitor of necroptosis), which significantly abolished the CU extract-induced necroptotic effect. Conclusions: The CU extract exhibits great potential in preventing breast cancer and thus warrants further investigations in vivo.Neeladrisingha DasSubhashish SamantarayChandrachur GhoshKomal KushwahaDebabrata SircarPartha RoyElsevierarticleCimaphila umbellataMCF-7 cellsAnti-angiogenesisAnti-cancerClonogenic assayOther systems of medicineRZ201-999ENPhytomedicine Plus, Vol 2, Iss 1, Pp 100159- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cimaphila umbellata MCF-7 cells Anti-angiogenesis Anti-cancer Clonogenic assay Other systems of medicine RZ201-999
spellingShingle	Cimaphila umbellata MCF-7 cells Anti-angiogenesis Anti-cancer Clonogenic assay Other systems of medicine RZ201-999 Neeladrisingha Das Subhashish Samantaray Chandrachur Ghosh Komal Kushwaha Debabrata Sircar Partha Roy Chimaphila umbellata extract exerts anti-proliferative effect on human breast cancer cells via RIP1K/RIP3K-mediated necroptosis
description	Background: Chimaphila umbellata (CU) is a small perennial plant whose roots and leaves are used in the preparation of homeopathic medicines. In this study, the anti-proliferative and apoptotic effects of CU extract, obtained from its homeopathic mother tincture, were evaluated in human breast cancer cell lines. Methods: MTT assay was used to evaluate the dose- and time-dependent cytotoxicity of the extract in MCF-7 and HEK293 cells. The anti-proliferative effect of the extract was evaluated using the clonogenic and wound healing assays. The anti-angiogenic activity of the drug was evaluated using the chick chorioallantoic membrane assay. The mode of cell death was analyzed using Annexin V and PI staining assays through flow cytometry. In addition, the expression patterns of associated genes were evaluated using immunoblot analysis. Results: CU extracts exerted anti-proliferative effect in breast cancer cell line, i.e., MCF-7 cells, by inhibiting their growth and migration. The extract also demonstrated significant anti-angiogenic ability, limiting the de-novo blood vessel growth and development in chick embryos. The extract was found to increase caspase-independent necroptosis by involving RIP1/RIP3 kinases and MLKL proteins. This finding was further confirmed by using NEC-1 (an inhibitor of necroptosis), which significantly abolished the CU extract-induced necroptotic effect. Conclusions: The CU extract exhibits great potential in preventing breast cancer and thus warrants further investigations in vivo.
format	article
author	Neeladrisingha Das Subhashish Samantaray Chandrachur Ghosh Komal Kushwaha Debabrata Sircar Partha Roy
author_facet	Neeladrisingha Das Subhashish Samantaray Chandrachur Ghosh Komal Kushwaha Debabrata Sircar Partha Roy
author_sort	Neeladrisingha Das
title	Chimaphila umbellata extract exerts anti-proliferative effect on human breast cancer cells via RIP1K/RIP3K-mediated necroptosis
title_short	Chimaphila umbellata extract exerts anti-proliferative effect on human breast cancer cells via RIP1K/RIP3K-mediated necroptosis
title_full	Chimaphila umbellata extract exerts anti-proliferative effect on human breast cancer cells via RIP1K/RIP3K-mediated necroptosis
title_fullStr	Chimaphila umbellata extract exerts anti-proliferative effect on human breast cancer cells via RIP1K/RIP3K-mediated necroptosis
title_full_unstemmed	Chimaphila umbellata extract exerts anti-proliferative effect on human breast cancer cells via RIP1K/RIP3K-mediated necroptosis
title_sort	chimaphila umbellata extract exerts anti-proliferative effect on human breast cancer cells via rip1k/rip3k-mediated necroptosis
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/04ce1685dc01485ab59c25c502d2e33a
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Chimaphila umbellata extract exerts anti-proliferative effect on human breast cancer cells via RIP1K/RIP3K-mediated necroptosis

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