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

Autor(es)

Machado, Ana Rita Thomazela ; Tuttis, Katiuska ; Santos, Patrick Wellington da Silva ; Aissa, Alexandre Ferro ; Antunes, Lusania Maria Greggi

• Tipo de documento: Artigo Científico
• Fonte: PHARMACEUTICS; v. 14, n. 12, p. 18-pg., 2022-12-01.

Resumo

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 mu M) and sorafenib (SORA; 8 mu M), 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. (AU)

• Processo FAPESP: 19/08348-2 - Avaliação toxicogenética do dissulfeto de dialila associado ao agente quimioterápico sorafenibe: investigação de morte celular e expressão de proteínas em células hepáticas humanas in vitro
• Beneficiário: Ana Rita Thomazela Machado
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/24576-0 - Efeitos dos nutracêuticos sulforafano, dissulfeto de dialila e vitamina D em linhagens tumorais humanas: Avaliação de citotoxicidade, genotoxicidade, migração celular, alterações epigenéticas e expressão gênica
• Beneficiário: Lusânia Maria Greggi Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Regular