Mechanistic Insight into Apoptotic Induction in Human Rhabdomyosarcoma and Breast Adenocarcinoma Cells by Chnoospora minima: A Sri Lankan Brown Seaweed

The current study determined the cytotoxic and apoptotic potential of the polyphenol-rich methanol extract of Chnoospora minima (C. minima) and its fractions against human breast adenocarcinoma (MCF-7) and rhabdomyosarcoma (RMS) cells. MTT and neutral red assays...

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Autores principales:	Thilina Lakmini Gunathilaka, Kulathungage Hiranthi Dilrangi, Pathmasiri Ranasinghe, Kalpa W. Samarakoon, L. Dinithi C. Peiris
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	RMS MCF-7 <i>Chnoospora minima</i> apoptosis cytotoxicity caspase pathway Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/a23366e4f3fb4fbfa605b69c089faa08
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spelling	oai:doaj.org-article:a23366e4f3fb4fbfa605b69c089faa082021-11-25T18:39:46ZMechanistic Insight into Apoptotic Induction in Human Rhabdomyosarcoma and Breast Adenocarcinoma Cells by <i>Chnoospora minima</i>: A Sri Lankan Brown Seaweed10.3390/ph141111541424-8247https://doaj.org/article/a23366e4f3fb4fbfa605b69c089faa082021-11-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1154https://doaj.org/toc/1424-8247The current study determined the cytotoxic and apoptotic potential of the polyphenol-rich methanol extract of <i>Chnoospora minima</i> (<i>C. minima</i>) and its fractions against human breast adenocarcinoma (MCF-7) and rhabdomyosarcoma (RMS) cells. MTT and neutral red assays were used to determine cytotoxicity. The clonogenic assay evaluated the antineoplastic activity, while the apoptotic activity was determined by cellular morphological changes, caspase 3/7 activity, and DNA fragmentation. Morphological alterations in apoptosis were observed by an inverted phase-contrast microscope and Hoechst 33342 staining methods. The total phenolic, flavonoids, alkaloids, and antioxidant activity in the hexane and chloroform fractions were determined, based on their cytotoxic activity. The hexane fraction of <i>C. minima</i> effectively reduced the cell growth that is concentration-dependent in human RMS and MCF-7 cell lines. It also exhibited low cytotoxicity on Vero cells. The characteristic cellular and nuclear apoptotic morphological features were observed. A noticeable caspase 3/7 activation and the fragmented DNA were detected only in the hexane fraction treated RMS cells, whereas MCF-7 cells showed low caspase 3/7 activation due to a lack of caspase 3 and no evidence of having a typical ladder pattern of apoptosis. Further analysis revealed that the hexane fraction-treated RMS cells upregulated the <i>p53</i> gene twofold (2.72) compared to the <i>p21</i> (0.77) gene, whereas in the MCF-7 cells, a 2.21-fold upregulation of <i>p53</i> was observed compared to the <i>p21</i> (0.64) gene. The hexane fraction exhibited moderate total phenolics, flavonoids, alkaloids content, and antioxidant activity. According to the different antioxidant mechanisms, hexane and chloroform fractions showed the highest antioxidant activities by FRAP and ORAC assays, respectively. GC-MS analysis of hexane fraction revealed the presence of methyl tetradecanoate (38.314%) as the most abundant compound. The study’s findings highlighted that the non-polar compounds present in the hexane fraction of <i>C. minima</i> suppressed cell proliferation and induced apoptosis-mediated cell death in RMS and MCF-7 cells, mainly via the activation of the <i>p53</i> gene. Hence, the isolation of compounds is warranted. However, more studies are required to understand the mechanistic insights of these observations.Thilina Lakmini GunathilakaKulathungage Hiranthi DilrangiPathmasiri RanasingheKalpa W. SamarakoonL. Dinithi C. PeirisMDPI AGarticleRMSMCF-7<i>Chnoospora minima</i>apoptosiscytotoxicitycaspase pathwayMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1154, p 1154 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	RMS MCF-7 <i>Chnoospora minima</i> apoptosis cytotoxicity caspase pathway Medicine R Pharmacy and materia medica RS1-441
spellingShingle	RMS MCF-7 <i>Chnoospora minima</i> apoptosis cytotoxicity caspase pathway Medicine R Pharmacy and materia medica RS1-441 Thilina Lakmini Gunathilaka Kulathungage Hiranthi Dilrangi Pathmasiri Ranasinghe Kalpa W. Samarakoon L. Dinithi C. Peiris Mechanistic Insight into Apoptotic Induction in Human Rhabdomyosarcoma and Breast Adenocarcinoma Cells by <i>Chnoospora minima</i>: A Sri Lankan Brown Seaweed
description	The current study determined the cytotoxic and apoptotic potential of the polyphenol-rich methanol extract of <i>Chnoospora minima</i> (<i>C. minima</i>) and its fractions against human breast adenocarcinoma (MCF-7) and rhabdomyosarcoma (RMS) cells. MTT and neutral red assays were used to determine cytotoxicity. The clonogenic assay evaluated the antineoplastic activity, while the apoptotic activity was determined by cellular morphological changes, caspase 3/7 activity, and DNA fragmentation. Morphological alterations in apoptosis were observed by an inverted phase-contrast microscope and Hoechst 33342 staining methods. The total phenolic, flavonoids, alkaloids, and antioxidant activity in the hexane and chloroform fractions were determined, based on their cytotoxic activity. The hexane fraction of <i>C. minima</i> effectively reduced the cell growth that is concentration-dependent in human RMS and MCF-7 cell lines. It also exhibited low cytotoxicity on Vero cells. The characteristic cellular and nuclear apoptotic morphological features were observed. A noticeable caspase 3/7 activation and the fragmented DNA were detected only in the hexane fraction treated RMS cells, whereas MCF-7 cells showed low caspase 3/7 activation due to a lack of caspase 3 and no evidence of having a typical ladder pattern of apoptosis. Further analysis revealed that the hexane fraction-treated RMS cells upregulated the <i>p53</i> gene twofold (2.72) compared to the <i>p21</i> (0.77) gene, whereas in the MCF-7 cells, a 2.21-fold upregulation of <i>p53</i> was observed compared to the <i>p21</i> (0.64) gene. The hexane fraction exhibited moderate total phenolics, flavonoids, alkaloids content, and antioxidant activity. According to the different antioxidant mechanisms, hexane and chloroform fractions showed the highest antioxidant activities by FRAP and ORAC assays, respectively. GC-MS analysis of hexane fraction revealed the presence of methyl tetradecanoate (38.314%) as the most abundant compound. The study’s findings highlighted that the non-polar compounds present in the hexane fraction of <i>C. minima</i> suppressed cell proliferation and induced apoptosis-mediated cell death in RMS and MCF-7 cells, mainly via the activation of the <i>p53</i> gene. Hence, the isolation of compounds is warranted. However, more studies are required to understand the mechanistic insights of these observations.
format	article
author	Thilina Lakmini Gunathilaka Kulathungage Hiranthi Dilrangi Pathmasiri Ranasinghe Kalpa W. Samarakoon L. Dinithi C. Peiris
author_facet	Thilina Lakmini Gunathilaka Kulathungage Hiranthi Dilrangi Pathmasiri Ranasinghe Kalpa W. Samarakoon L. Dinithi C. Peiris
author_sort	Thilina Lakmini Gunathilaka
title	Mechanistic Insight into Apoptotic Induction in Human Rhabdomyosarcoma and Breast Adenocarcinoma Cells by <i>Chnoospora minima</i>: A Sri Lankan Brown Seaweed
title_short	Mechanistic Insight into Apoptotic Induction in Human Rhabdomyosarcoma and Breast Adenocarcinoma Cells by <i>Chnoospora minima</i>: A Sri Lankan Brown Seaweed
title_full	Mechanistic Insight into Apoptotic Induction in Human Rhabdomyosarcoma and Breast Adenocarcinoma Cells by <i>Chnoospora minima</i>: A Sri Lankan Brown Seaweed
title_fullStr	Mechanistic Insight into Apoptotic Induction in Human Rhabdomyosarcoma and Breast Adenocarcinoma Cells by <i>Chnoospora minima</i>: A Sri Lankan Brown Seaweed
title_full_unstemmed	Mechanistic Insight into Apoptotic Induction in Human Rhabdomyosarcoma and Breast Adenocarcinoma Cells by <i>Chnoospora minima</i>: A Sri Lankan Brown Seaweed
title_sort	mechanistic insight into apoptotic induction in human rhabdomyosarcoma and breast adenocarcinoma cells by <i>chnoospora minima</i>: a sri lankan brown seaweed
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a23366e4f3fb4fbfa605b69c089faa08
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Mechanistic Insight into Apoptotic Induction in Human Rhabdomyosarcoma and Breast Adenocarcinoma Cells by <i>Chnoospora minima</i>: A Sri Lankan Brown Seaweed

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