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Updated: Jun 23, 2026
An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Diallyl Disulfide Induces Chemosensitization to Sorafenib, Autophagy, and Cell Cycle Arrest and Inhibits Invasion in
Ana Rita Thomazela Machado1, Katiuska Tuttis2, Patrick Wellington da Silva Santos1
1Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-904, SP, Brazil.
Abstract:
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.
Insights
The combination of diallyl disulfide (DADS) and sorafenib (SORA) shows promise for treating hepatocellular carcinoma. This DADS + SORA therapy effectively reduced cancer cell invasion and proliferation in vitro.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Hepatocellular carcinoma (HCC) is a prevalent cancer with limited therapeutic options.
- Combining chemotherapeutics with plant-derived compounds is a potential cancer treatment strategy.
Purpose of the Study:
- To investigate the in vitro efficacy of diallyl disulfide (DADS) and sorafenib (SORA) alone and in combination against hepatocellular carcinoma cells (HepG2).
- To evaluate the impact of DADS and SORA on cancer cell death, cell cycle, gene/protein expression, and tumorigenesis.
Main Methods:
- In vitro assays including LIVE/DEAD, autophagy, flow cytometry, RT-qPCR, Western blot, clonogenic assay, and wound healing.
- Assessment of cell proliferation, migration, invasion, and expression of key molecular markers.
Main Results:
- The DADS + SORA combination induced autophagic cell death by modulating LC3, NRF2, FOS, and TNF expression.
- This combination led to G1 phase cell cycle arrest, upregulating CHEK2 expression, and inhibited invasion via MMP2 downregulation.
- Predictive analysis suggested MAPK pathway involvement.
Conclusions:
- The DADS + SORA combination effectively suppressed hepatocellular carcinoma cell invasion, proliferation, and survival in vitro.
- This combination therapy demonstrates potential for dampening tumor growth and metastatic capabilities, suggesting its utility in future clinical protocols.
