Cryptocaryone Promotes ROS-Dependent Antiproliferation and Apoptosis in Ovarian Cancer Cells

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.

Antibladder Cancer Effects of Excavatolide C by Inducing Oxidative Stress, Apoptosis, and DNA Damage In Vitro

“…Oxidative stress-generating drugs commonly inhibit cancer cell proliferation [ 30 , 31 , 32 , 33 ]. For example, cryptocaryone triggers ROS and apoptosis to inhibit the proliferation of ovarian cancer cells [ 34 ]. A marine natural product such as fucoidan can upregulate oxidative stress and consequently induce apoptosis and cause antiproliferation of oral cancer cells [ 33 ].…”

“…Oxidative stress may evoke several cellular responses, such as apoptosis [ 39 ] and DNA damage [ 31 ]. For example, cryptocaryone-induced ROS promotes apoptosis and DNA damage in ovarian cancer cells [ 34 ]. Similarly, EXCC triggers apoptosis as evidenced by the cell cycle, annexin V, and caspase signaling ( Figure 2 , Figure 3 and Figure 4 ).…”

Methanol Extract of Clavularia inflata Exerts Apoptosis and DNA Damage to Oral Cancer Cells

“…Several literature reports prove that NAC recovers drug-induced oxidative stress-associated changes. For example, natural products such as fucoidan [ 9 ] and cryptocaryone [ 54 ] show oxidative stress-dependent mechanisms in oral and ovarian cancer cells, validated by NAC. In the present investigation, the MECI-promoting mechanism for oxidative stress, apoptosis, and DNA damage was blocked by NAC.…”

The Genus Cryptocarya: A Review on Phytochemistry and Pharmacological Activities

“…[118] Pdcd4 (programmed cell death 4) is classified as a novel tumor suppressor protein that can inhibit transformation, migration, and invasion of cancer cells. [72] Pdcd4-stabilizing activity of serial new α-pyrones cryptocaryols A-H (118)(119)(120)(121)(122)(123)(124)(125) was associated with the EC 50 values of 1.3-4.9 μM, when rapamycin was used as a standard (EC 50 0.05 μM). [72] Three phenolics dihydrosinapyl ferulate (333), 9,9'-Odi-feruloyl-(À )-secoisolariciresinol (342), and rhusemialin A (348) were the next tested cytotoxic agents, by which they were associated with the IC 50 values of 3.5-35.74 μM against HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cancer cell lines.…”