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Cryptocaryone Promotes ROS-Dependent Antiproliferation and Apoptosis in Ovarian Cancer Cells
Yu-Chieh Chen1, Che-Wei Yang2, Te-Fu Chan1,3
1Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
Abstract:
Cryptocaryone (CPC) is a bioactive dihydrochalcone derived from Cryptocarya plants, and its antiproliferation was rarely reported, especially for ovarian cancer (OVCA). This study aimed to examine the regulation ability and mechanism of CPC on three histotypes of OVCA cells (SKOV3, TOV-21G, and TOV-112D). In a 24 h MTS assay, CPC showed antiproliferation effects to OVCA cells, i.e., IC50 values 1.5, 3, and 9.5 μM for TOV-21G, SKOV3, and TOV-112D cells. TOV-21G and SKOV3 cells showed hypersensitivity to CPC when applied for exposure time and concentration experiments. For biological processes, CPC stimulated the generation of reactive oxygen species and mitochondrial superoxide and promoted mitochondrial membrane potential dysfunction in TOV-21G and SKOV3 cells. Apoptosis was detected in OVCA cells through subG1 accumulation and annexin V staining. Apoptosis signaling such as caspase 3/7 activities, cleaved poly (ADP-ribose) polymerase, and caspase 3 expressions were upregulated by CPC. Specifically, the intrinsic and extrinsic apoptotic caspase 9 and caspase 8 were overexpressed in OVCA cells following CPC treatment. Moreover, CPC also stimulated DNA damages in terms of γH2AX expression and increased γH2AX foci. CPC also induced 8-hydroxy-2'-deoxyguanosine DNA damages. These CPC-associated principal biological processes were validated to be oxidative stress-dependent by N-acetylcysteine. In conclusion, CPC is a potential anti-OVCA natural product showing oxidative stress-dependent antiproliferation, apoptosis, and DNA damaging functions.
Insights
Cryptocaryone (CPC) demonstrates anticancer effects against ovarian cancer (OVCA) by inducing oxidative stress, apoptosis, and DNA damage. This natural compound shows potential as an anti-OVCA therapeutic agent.
Area of Science:
- Natural Products Chemistry
- Molecular Biology
- Cancer Research
Background:
- Cryptocaryone (CPC), a dihydrochalcone from *Cryptocarya* plants, has limited reported antiproliferation activity, particularly against ovarian cancer (OVCA).
- Understanding CPC's mechanism against OVCA is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the antiproliferative effects and underlying mechanisms of CPC on three distinct human ovarian cancer cell lines (SKOV3, TOV-21G, TOV-112D).
- To elucidate the role of oxidative stress in CPC-induced cellular responses.
Main Methods:
- Cell viability was assessed using MTS assays to determine IC50 values.
- Reactive oxygen species (ROS) generation, mitochondrial dysfunction, and apoptosis were evaluated through various assays.
- DNA damage was quantified by measuring γH2AX expression and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels.
- The role of oxidative stress was confirmed using N-acetylcysteine (NAC).
Main Results:
- CPC exhibited significant antiproliferative effects against OVCA cells, with varying sensitivities observed across cell lines.
- CPC treatment led to increased ROS production, mitochondrial membrane potential dysfunction, and apoptosis induction.
- CPC significantly induced DNA damage, evidenced by elevated γH2AX and 8-OHdG.
- The observed biological effects were confirmed to be dependent on oxidative stress.
Conclusions:
- Cryptocaryone possesses potent anti-OVCA properties mediated by oxidative stress.
- CPC induces apoptosis and DNA damage in ovarian cancer cells.
- CPC represents a promising natural product for further investigation as an anti-ovarian cancer agent.
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