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.