Co-SLD suppressed the growth of oral squamous cell carcinoma via disrupting mitochondrial function

Area of Science:

• Pharmacology and Toxicology
• Cancer Biology
• Developmental Biology

Background:

• Novel cobalt complexes are being explored for therapeutic applications.
• Sulindac is a non-steroidal anti-inflammatory drug with potential anticancer properties.
• Understanding the safety and efficacy of novel drug candidates is crucial.

Purpose of the Study:

• To evaluate the developmental toxicity of a novel cobalt-sulindac complex (Co-SLD) in zebrafish.
• To assess the antitumor efficacy of Co-SLD against oral squamous cell carcinoma (CAL27).
• To elucidate the mechanism of action of Co-SLD in cancer cells.

Main Methods:

• Zebrafish embryos were exposed to varying concentrations of Co-SLD (5-20 μM) from 3-144 hours post-fertilization.
• Oral squamous cell carcinoma CAL27 cells were treated with Co-SLD (10 and 20 μM).
• Cell viability, migration, mitochondrial membrane potential, reactive oxygen species (ROS) levels, and ATP depletion were assessed.

Main Results:

• Co-SLD exhibited no significant toxicity in zebrafish at 5 and 10 μM, but caused mortality, malformation, and developmental delays at 20 μM.
• Co-SLD significantly inhibited CAL27 cell growth and migration at 10 and 20 μM.
• Mitochondrial damage, including decreased membrane potential, increased ROS, and ATP depletion, was observed in treated cancer cells.

Conclusions:

• Co-SLD demonstrates a dual effect: low concentrations are safe in developmental models, while higher concentrations exhibit potent anticancer activity.
• The anticancer mechanism of Co-SLD involves the induction of mitochondrial dysfunction in oral cancer cells.
• A concentration of 10 μM Co-SLD represents an optimal balance between efficacy against cancer cells and minimal toxicity to normal tissues.