Reactive oxygen species mediate soft corals-derived sinuleptolide-induced antiproliferation and DNA damage in oral
Yung-Ting Chang1,2, Chiung-Yao Huang3, Jen-Yang Tang4,5
1Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University, Kaohsiung, Taiwan.
Abstract:
We previously reported that the soft coral-derived bioactive substance, sinuleptolide, can inhibit the proliferation of oral cancer cells in association with oxidative stress. The functional role of oxidative stress in the cell-killing effect of sinuleptolide on oral cancer cells was not investigated as yet. To address this question, we introduced the reactive oxygen species (ROS) scavenger (N-acetylcysteine [NAC]) in a pretreatment to evaluate the sinuleptolide-induced changes to cell viability, morphology, intracellular ROS, mitochondrial superoxide, apoptosis, and DNA damage of oral cancer cells (Ca9-22). After sinuleptolide treatment, antiproliferation, apoptosis-like morphology, ROS/mitochondrial superoxide generation, annexin V-based apoptosis, and γH2AX-based DNA damage were induced. All these changes were blocked by NAC pretreatment at 4 mM for 1 h. This showed that the cell-killing mechanism of oral cancer cells of sinuleptolide is ROS dependent.
Insights
Sinuleptolide, a compound from soft coral, kills oral cancer cells by increasing reactive oxygen species (ROS). Blocking ROS with N-acetylcysteine (NAC) prevented this cell death, confirming ROS dependence.
Area of Science:
- Marine natural products
- Cancer biology
- Oxidative stress
Background:
- Sinuleptolide, a bioactive substance from soft coral, inhibits oral cancer cell proliferation.
- The precise role of oxidative stress in sinuleptolide's cytotoxic effects remains unclear.
Purpose of the Study:
- To investigate the functional role of reactive oxygen species (ROS) in sinuleptolide-induced oral cancer cell death.
- To determine if ROS scavenging can mitigate sinuleptolide's effects on oral cancer cells.
Main Methods:
- Oral cancer cells (Ca9-22) were pretreated with N-acetylcysteine (NAC), a ROS scavenger.
- Cells were subsequently treated with sinuleptolide to assess effects on cell viability, morphology, ROS levels, mitochondrial superoxide, apoptosis, and DNA damage.
- Key markers included annexin V for apoptosis and γH2AX for DNA damage.
Main Results:
- Sinuleptolide treatment induced significant antiproliferation, apoptosis-like morphology, and increased intracellular ROS and mitochondrial superoxide.
- Sinuleptolide also triggered annexin V-positive apoptosis and γH2AX-positive DNA damage.
- Pretreatment with NAC completely blocked all sinuleptolide-induced changes, including antiproliferation and apoptosis.
Conclusions:
- The cell-killing mechanism of sinuleptolide against oral cancer cells is critically dependent on the generation of ROS.
- Targeting ROS pathways represents a potential therapeutic strategy for oral cancer treatment using sinuleptolide.
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