Hydrogen peroxide derived from marine peroxy sesquiterpenoids induces apoptosis in HCT116 human colon cancer cells
Haruna Miyazato1, Junsei Taira1, Katsuhiro Ueda2
1Department of Bioresource Technology, Okinawa National College of Technology, 905 Henoko, Nago-shi, Okinawa 905-2192, Japan.
Abstract:
In this study, the isolates of the peroxy sesquiterpenoids (1-3) from the Okinawan soft coral, Sinularia sp., indicated cytotoxicity in HCT116 colon cancer cells. The apoptotic cells with a nuclear condensation were detected in the presence of these compounds, then the caspase 3/7 activity was induced, indicating that the compounds have a potential antitumor activity by apoptosis-induction. The cells treated with these compounds were generated reactive oxygen species (ROS), indicating that the ROS is related to the induction of apoptosis. The ROS production reduced in the presence of catalase or trolox, indicating that hydrogen peroxide (H2O2) is generated through a certain free radical reaction derived from the compound. In fact, the accumulation of intracellular H2O2 was also confirmed in the presence of these compounds. Based on all the results, this study proposed the apoptosis-inducing mechanism due to the compounds that the H2O2 produced involving free radical reactions derived from cleavage of the end or hydro-peroxide in the molecule induced cell death.
Insights
Peroxy sesquiterpenoids from soft coral exhibit antitumor potential by inducing apoptosis in colon cancer cells. This cell death mechanism involves reactive oxygen species generation, specifically hydrogen peroxide, linked to compound molecular structure.
Area of Science:
- Marine Natural Products Chemistry
- Cancer Biology
- Cellular Signaling
Background:
- Soft corals are a rich source of bioactive compounds.
- Peroxy sesquiterpenoids represent a class of natural products with potential pharmacological activities.
- Colon cancer remains a significant global health challenge requiring novel therapeutic strategies.
Purpose of the Study:
- To investigate the cytotoxic effects of peroxy sesquiterpenoids isolated from Sinularia sp. on HCT116 colon cancer cells.
- To elucidate the mechanism of action underlying the observed cytotoxicity, focusing on apoptosis induction and reactive oxygen species (ROS) generation.
- To explore the role of hydrogen peroxide (H2O2) in the apoptosis-inducing pathway.
Main Methods:
- Isolation and structural elucidation of peroxy sesquiterpenoids from Okinawan soft coral Sinularia sp.
- Cytotoxicity assays using HCT116 colon cancer cell lines.
- Assessment of apoptosis using nuclear condensation and caspase 3/7 activity assays.
- Measurement of reactive oxygen species (ROS) and intracellular hydrogen peroxide (H2O2) levels.
- Inhibition studies using antioxidants like catalase and trolox.
Main Results:
- Isolated compounds 1-3 demonstrated significant cytotoxicity against HCT116 colon cancer cells.
- Treatment with these compounds induced apoptosis, characterized by nuclear condensation and caspase 3/7 activation.
- A notable increase in reactive oxygen species (ROS) production was observed in treated cells.
- ROS production was mitigated by catalase and trolox, implicating hydrogen peroxide (H2O2) as a key mediator.
- Intracellular H2O2 accumulation was confirmed, suggesting its generation through free radical reactions from the compounds.
Conclusions:
- The studied peroxy sesquiterpenoids possess potent antitumor activity against colon cancer cells via apoptosis induction.
- Hydrogen peroxide (H2O2) generated through free radical reactions, likely from the cleavage of the peroxy group, plays a crucial role in mediating this apoptosis.
- These findings highlight the therapeutic potential of marine-derived peroxy sesquiterpenoids and elucidate their cell death mechanism.
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