Cargando…

Diallyl Disulfide Induces Chemosensitization to Sorafenib, Autophagy, and Cell Cycle Arrest and Inhibits Invasion in Hepatocellular Carcinoma

Hepatocellular carcinoma is the seventh most common type of cancer in the world, with limited treatment options. A promising strategy to treat cancer is to associate chemotherapeutics and plant bioactive compounds. Here, we examined whether diallyl disulfide (DADS; 50–200 μM) and sorafenib (SORA; 8...

Descripción completa

Detalles Bibliográficos
Autores principales: Machado, Ana Rita Thomazela, Tuttis, Katiuska, Santos, Patrick Wellington da Silva, Aissa, Alexandre Ferro, Antunes, Lusânia Maria Greggi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788602/
https://www.ncbi.nlm.nih.gov/pubmed/36559076
http://dx.doi.org/10.3390/pharmaceutics14122582
_version_ 1784858793911255040
author Machado, Ana Rita Thomazela
Tuttis, Katiuska
Santos, Patrick Wellington da Silva
Aissa, Alexandre Ferro
Antunes, Lusânia Maria Greggi
author_facet Machado, Ana Rita Thomazela
Tuttis, Katiuska
Santos, Patrick Wellington da Silva
Aissa, Alexandre Ferro
Antunes, Lusânia Maria Greggi
author_sort Machado, Ana Rita Thomazela
collection PubMed
description Hepatocellular carcinoma is the seventh most common type of cancer in the world, with limited treatment options. A promising strategy to treat cancer is to associate chemotherapeutics and plant bioactive compounds. Here, we examined whether diallyl disulfide (DADS; 50–200 μM) and sorafenib (SORA; 8 μM), either alone or in combination, were toxic to hepatocellular carcinoma cells (HepG2) in vitro. We assessed whether DADS and/or SORA induced cell death (LIVE/DEAD assay and autophagy) and cell cycle changes (flow cytometry), altered expression of key genes and proteins (RT-qPCR and Western blot), and modulated tumorigenesis signatures, such as proliferation (clonogenic assay), migration (wound healing), and invasion (inserts). The DADS + SORA combination elicited autophagic cell death by upregulating LC3 and NRF2 expression and downregulating FOS and TNF expression; induced the accumulation of cells in the G1 phase which thereby upregulated the CHEK2 expression; and inhibited invasion by downregulating the MMP2 expression. Predictive analysis indicated the participation of the MAPK pathway in the reported results. The DADS + SORA combination suppressed both cell invasion and clonogenic survival, which indicated that it dampened tumor growth, proliferation, invasion, and metastatic potential. Therefore, the DADS + SORA combination is a promising therapy to develop new clinical protocols.
format Online
Article
Text
id pubmed-9788602
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-97886022022-12-24 Diallyl Disulfide Induces Chemosensitization to Sorafenib, Autophagy, and Cell Cycle Arrest and Inhibits Invasion in Hepatocellular Carcinoma Machado, Ana Rita Thomazela Tuttis, Katiuska Santos, Patrick Wellington da Silva Aissa, Alexandre Ferro Antunes, Lusânia Maria Greggi Pharmaceutics Article Hepatocellular carcinoma is the seventh most common type of cancer in the world, with limited treatment options. A promising strategy to treat cancer is to associate chemotherapeutics and plant bioactive compounds. Here, we examined whether diallyl disulfide (DADS; 50–200 μM) and sorafenib (SORA; 8 μM), either alone or in combination, were toxic to hepatocellular carcinoma cells (HepG2) in vitro. We assessed whether DADS and/or SORA induced cell death (LIVE/DEAD assay and autophagy) and cell cycle changes (flow cytometry), altered expression of key genes and proteins (RT-qPCR and Western blot), and modulated tumorigenesis signatures, such as proliferation (clonogenic assay), migration (wound healing), and invasion (inserts). The DADS + SORA combination elicited autophagic cell death by upregulating LC3 and NRF2 expression and downregulating FOS and TNF expression; induced the accumulation of cells in the G1 phase which thereby upregulated the CHEK2 expression; and inhibited invasion by downregulating the MMP2 expression. Predictive analysis indicated the participation of the MAPK pathway in the reported results. The DADS + SORA combination suppressed both cell invasion and clonogenic survival, which indicated that it dampened tumor growth, proliferation, invasion, and metastatic potential. Therefore, the DADS + SORA combination is a promising therapy to develop new clinical protocols. MDPI 2022-11-24 /pmc/articles/PMC9788602/ /pubmed/36559076 http://dx.doi.org/10.3390/pharmaceutics14122582 Text en © 2022 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
Machado, Ana Rita Thomazela
Tuttis, Katiuska
Santos, Patrick Wellington da Silva
Aissa, Alexandre Ferro
Antunes, Lusânia Maria Greggi
Diallyl Disulfide Induces Chemosensitization to Sorafenib, Autophagy, and Cell Cycle Arrest and Inhibits Invasion in Hepatocellular Carcinoma
title Diallyl Disulfide Induces Chemosensitization to Sorafenib, Autophagy, and Cell Cycle Arrest and Inhibits Invasion in Hepatocellular Carcinoma
title_full Diallyl Disulfide Induces Chemosensitization to Sorafenib, Autophagy, and Cell Cycle Arrest and Inhibits Invasion in Hepatocellular Carcinoma
title_fullStr Diallyl Disulfide Induces Chemosensitization to Sorafenib, Autophagy, and Cell Cycle Arrest and Inhibits Invasion in Hepatocellular Carcinoma
title_full_unstemmed Diallyl Disulfide Induces Chemosensitization to Sorafenib, Autophagy, and Cell Cycle Arrest and Inhibits Invasion in Hepatocellular Carcinoma
title_short Diallyl Disulfide Induces Chemosensitization to Sorafenib, Autophagy, and Cell Cycle Arrest and Inhibits Invasion in Hepatocellular Carcinoma
title_sort diallyl disulfide induces chemosensitization to sorafenib, autophagy, and cell cycle arrest and inhibits invasion in hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788602/
https://www.ncbi.nlm.nih.gov/pubmed/36559076
http://dx.doi.org/10.3390/pharmaceutics14122582
work_keys_str_mv AT machadoanaritathomazela diallyldisulfideinduceschemosensitizationtosorafenibautophagyandcellcyclearrestandinhibitsinvasioninhepatocellularcarcinoma
AT tuttiskatiuska diallyldisulfideinduceschemosensitizationtosorafenibautophagyandcellcyclearrestandinhibitsinvasioninhepatocellularcarcinoma
AT santospatrickwellingtondasilva diallyldisulfideinduceschemosensitizationtosorafenibautophagyandcellcyclearrestandinhibitsinvasioninhepatocellularcarcinoma
AT aissaalexandreferro diallyldisulfideinduceschemosensitizationtosorafenibautophagyandcellcyclearrestandinhibitsinvasioninhepatocellularcarcinoma
AT antuneslusaniamariagreggi diallyldisulfideinduceschemosensitizationtosorafenibautophagyandcellcyclearrestandinhibitsinvasioninhepatocellularcarcinoma