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Updated: Mar 3, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
In Vitro and In Vivo Antimetastatic Effect of Glutathione Disulfide Liposomes
Satya S Sadhu1, Shenggang Wang1, Rakesh Dachineni1
1Department of Pharmaceutical Sciences, College of Pharmacy & Allied Health Professions, South Dakota State University, Brookings, SD, USA.
Abstract:
Cancer metastasis is the major cause of cancer mortality. Despite extensive research efforts, effective treatment for cancer metastasis is still lacking. Cancer metastasis involves 4 essential steps: cell detachment, migration, invasion, and adhesion. Detachment is the first and required step for metastasis. Glutathione disulfide (GSSG) is derived from the oxidation of glutathione (GSH), which is present in biological systems in millimolar concentration. Although GSSG is commercially available, the impact of GSSG on cell functions/dysfunctions has not been fully explored due to the fact that GSSG is not cell membrane permeable and a lack of method to specifically increase GSSG in cells. We have developed GSSG liposomes that effectively deliver GSSG to cells. Unexpectedly, cells treated with GSSG liposomes were resistant to detachment by trypsinization. This observation led to the investigation of the antimetastatic effect of GSSG liposomes. Our data demonstrate that GSSG liposomes at 1 mg/mL completely blocked cell detachment and migration, and significantly inhibited cancer cell invasion. Aqueous GSSG showed no such effect, confirming that the effects on cell detachment, migration, and invasion were caused by the intracellular delivery of GSSG. An in vivo experiment with a murine melanoma experimental metastasis model showed that GSSG liposomes prevented melanoma lung metastasis. The unique antimetastatic mechanism through the effects on detachment and migration, and effective in vitro and in vivo metastasis inhibition, warrants further investigation of the GSSG liposomes as a potential treatment for cancer metastasis.
Insights
Glutathione disulfide (GSSG) liposomes effectively deliver GSSG into cells, blocking cancer cell detachment and migration. These liposomes demonstrated significant inhibition of cancer metastasis in vitro and in vivo, offering a promising new therapeutic strategy.
Area of Science:
- Oncology
- Cell Biology
- Drug Delivery
Background:
- Cancer metastasis is a primary cause of cancer-related deaths, with limited effective treatments.
- Metastasis involves critical steps including cell detachment, migration, invasion, and adhesion.
- Glutathione disulfide (GSSG) has potential cellular effects, but its poor cell membrane permeability hindered research.
Purpose of the Study:
- To investigate the antimetastatic effects of GSSG delivered intracellularly using liposomes.
- To explore the mechanism by which GSSG impacts cancer cell detachment and migration.
- To evaluate the efficacy of GSSG liposomes in preclinical models of cancer metastasis.
Main Methods:
- Development of liposomes for intracellular delivery of GSSG.
- In vitro assessment of cancer cell detachment, migration, and invasion.
- In vivo evaluation of GSSG liposomes in a murine melanoma metastasis model.
Main Results:
- GSSG liposomes at 1 mg/mL completely inhibited cancer cell detachment and migration.
- Intracellular GSSG significantly suppressed cancer cell invasion.
- GSSG liposomes prevented melanoma lung metastasis in vivo, while aqueous GSSG had no effect.
Conclusions:
- Intracellular delivery of GSSG via liposomes is a viable strategy to inhibit cancer metastasis.
- GSSG liposomes exhibit a unique antimetastatic mechanism by targeting cell detachment and migration.
- GSSG liposomes represent a promising therapeutic candidate for treating cancer metastasis.
