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Alkaloid from Geissospermum sericeum Benth. & Hook.f. ex Miers (Apocynaceae) Induce Apoptosis by Caspase Pathway in Human Gastric Cancer Cells
Gastric cancer is among the major causes of death from neoplasia leading causes of death worldwide, with high incidence rates and problems related to its treatment. Here, we outline how Geissospermum sericeum exerts antitumor activity on the ACP02 cell line (human gastric adenocarcinoma) and the mec...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222982/ https://www.ncbi.nlm.nih.gov/pubmed/37242548 http://dx.doi.org/10.3390/ph16050765 |
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author | Carmo Bastos, Mirian Letícia Silva-Silva, João Victor Neves Cruz, Jorddy Palheta da Silva, Amanda Roberta Bentaberry-Rosa, Alexandre Augusto da Costa Ramos, Gisele de Sousa Siqueira, José Edson Coelho-Ferreira, Márlia Regina Percário, Sandro Santana Barbosa Marinho, Patrícia Marinho, Andrey Moacir do Rosario de Oliveira Bahia, Marcelo Dolabela, Maria Fâni |
author_facet | Carmo Bastos, Mirian Letícia Silva-Silva, João Victor Neves Cruz, Jorddy Palheta da Silva, Amanda Roberta Bentaberry-Rosa, Alexandre Augusto da Costa Ramos, Gisele de Sousa Siqueira, José Edson Coelho-Ferreira, Márlia Regina Percário, Sandro Santana Barbosa Marinho, Patrícia Marinho, Andrey Moacir do Rosario de Oliveira Bahia, Marcelo Dolabela, Maria Fâni |
author_sort | Carmo Bastos, Mirian Letícia |
collection | PubMed |
description | Gastric cancer is among the major causes of death from neoplasia leading causes of death worldwide, with high incidence rates and problems related to its treatment. Here, we outline how Geissospermum sericeum exerts antitumor activity on the ACP02 cell line (human gastric adenocarcinoma) and the mechanism of cell death. The ethanol extract and fractions, neutral fraction and alkaloid fraction, were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid (geissoschizoline N4-methylchlorine) identified by NMR. The cytotoxicity activity of the samples (ethanol extract, neutral fraction, alkaloid fraction, and geissoschizoline N4-methylchlorine) in HepG2 and VERO cells was determined by MTT. The ACP02 cell line was used to assess the anticancer potential. Cell death was quantified with the fluorescent dyes Hoechst 33342, propidium iodide, and fluorescein diacetate. The geissoschizoline N4-methylchlorine was evaluated in silico against caspase 3 and 8. In the antitumor evaluation, there was observed a more significant inhibitory effect of the alkaloid fraction (IC50 18.29 µg/mL) and the geissoschizoline N4-methylchlorine (IC(50) 12.06 µg/mL). However, geissoschizoline N4-methylchlorine showed lower cytotoxicity in the VERO (CC(50) 476.0 µg/mL) and HepG2 (CC(50) 503.5 µg/mL) cell lines, with high selectivity against ACP02 cells (SI 39.47 and 41.75, respectively). The alkaloid fraction showed more significant apoptosis and necrosis in 24 h and 48 h, with increased necrosis in higher concentrations and increased exposure time. For the alkaloid, apoptosis and necrosis were concentration- and time-dependent, with a lower necrosis rate. Molecular modeling studies demonstrated that geissoschizoline N4-methylchlorine could occupy the active site of caspases 3 and 8 energetically favorably. The results showed that fractionation contributed to the activity with pronounced selectivity for ACP02 cells, and geissoschizoline N4-methylchlor is a promising candidate for caspase inhibitors of apoptosis in gastric cancer. Thus, this study provides a scientific basis for the biological functions of Geissospermum sericeum, as well as demonstrates the potential of the geissoschizoline N4-methylchlorine in the treatment of gastric cancer. |
format | Online Article Text |
id | pubmed-10222982 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102229822023-05-28 Alkaloid from Geissospermum sericeum Benth. & Hook.f. ex Miers (Apocynaceae) Induce Apoptosis by Caspase Pathway in Human Gastric Cancer Cells Carmo Bastos, Mirian Letícia Silva-Silva, João Victor Neves Cruz, Jorddy Palheta da Silva, Amanda Roberta Bentaberry-Rosa, Alexandre Augusto da Costa Ramos, Gisele de Sousa Siqueira, José Edson Coelho-Ferreira, Márlia Regina Percário, Sandro Santana Barbosa Marinho, Patrícia Marinho, Andrey Moacir do Rosario de Oliveira Bahia, Marcelo Dolabela, Maria Fâni Pharmaceuticals (Basel) Article Gastric cancer is among the major causes of death from neoplasia leading causes of death worldwide, with high incidence rates and problems related to its treatment. Here, we outline how Geissospermum sericeum exerts antitumor activity on the ACP02 cell line (human gastric adenocarcinoma) and the mechanism of cell death. The ethanol extract and fractions, neutral fraction and alkaloid fraction, were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid (geissoschizoline N4-methylchlorine) identified by NMR. The cytotoxicity activity of the samples (ethanol extract, neutral fraction, alkaloid fraction, and geissoschizoline N4-methylchlorine) in HepG2 and VERO cells was determined by MTT. The ACP02 cell line was used to assess the anticancer potential. Cell death was quantified with the fluorescent dyes Hoechst 33342, propidium iodide, and fluorescein diacetate. The geissoschizoline N4-methylchlorine was evaluated in silico against caspase 3 and 8. In the antitumor evaluation, there was observed a more significant inhibitory effect of the alkaloid fraction (IC50 18.29 µg/mL) and the geissoschizoline N4-methylchlorine (IC(50) 12.06 µg/mL). However, geissoschizoline N4-methylchlorine showed lower cytotoxicity in the VERO (CC(50) 476.0 µg/mL) and HepG2 (CC(50) 503.5 µg/mL) cell lines, with high selectivity against ACP02 cells (SI 39.47 and 41.75, respectively). The alkaloid fraction showed more significant apoptosis and necrosis in 24 h and 48 h, with increased necrosis in higher concentrations and increased exposure time. For the alkaloid, apoptosis and necrosis were concentration- and time-dependent, with a lower necrosis rate. Molecular modeling studies demonstrated that geissoschizoline N4-methylchlorine could occupy the active site of caspases 3 and 8 energetically favorably. The results showed that fractionation contributed to the activity with pronounced selectivity for ACP02 cells, and geissoschizoline N4-methylchlor is a promising candidate for caspase inhibitors of apoptosis in gastric cancer. Thus, this study provides a scientific basis for the biological functions of Geissospermum sericeum, as well as demonstrates the potential of the geissoschizoline N4-methylchlorine in the treatment of gastric cancer. MDPI 2023-05-18 /pmc/articles/PMC10222982/ /pubmed/37242548 http://dx.doi.org/10.3390/ph16050765 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Carmo Bastos, Mirian Letícia Silva-Silva, João Victor Neves Cruz, Jorddy Palheta da Silva, Amanda Roberta Bentaberry-Rosa, Alexandre Augusto da Costa Ramos, Gisele de Sousa Siqueira, José Edson Coelho-Ferreira, Márlia Regina Percário, Sandro Santana Barbosa Marinho, Patrícia Marinho, Andrey Moacir do Rosario de Oliveira Bahia, Marcelo Dolabela, Maria Fâni Alkaloid from Geissospermum sericeum Benth. & Hook.f. ex Miers (Apocynaceae) Induce Apoptosis by Caspase Pathway in Human Gastric Cancer Cells |
title | Alkaloid from Geissospermum sericeum Benth. & Hook.f. ex Miers (Apocynaceae) Induce Apoptosis by Caspase Pathway in Human Gastric Cancer Cells |
title_full | Alkaloid from Geissospermum sericeum Benth. & Hook.f. ex Miers (Apocynaceae) Induce Apoptosis by Caspase Pathway in Human Gastric Cancer Cells |
title_fullStr | Alkaloid from Geissospermum sericeum Benth. & Hook.f. ex Miers (Apocynaceae) Induce Apoptosis by Caspase Pathway in Human Gastric Cancer Cells |
title_full_unstemmed | Alkaloid from Geissospermum sericeum Benth. & Hook.f. ex Miers (Apocynaceae) Induce Apoptosis by Caspase Pathway in Human Gastric Cancer Cells |
title_short | Alkaloid from Geissospermum sericeum Benth. & Hook.f. ex Miers (Apocynaceae) Induce Apoptosis by Caspase Pathway in Human Gastric Cancer Cells |
title_sort | alkaloid from geissospermum sericeum benth. & hook.f. ex miers (apocynaceae) induce apoptosis by caspase pathway in human gastric cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222982/ https://www.ncbi.nlm.nih.gov/pubmed/37242548 http://dx.doi.org/10.3390/ph16050765 |
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