Involvement of endoplasmic reticulum stress in isoliquiritigenin-induced SKOV-3 cell apoptosis

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Isoliquiritigenin (ISL), a chalconoid from licorice, exhibits chemopreventive properties and is patented for tumor treatment in China.
• Ovarian carcinoma SKOV-3 cells are a relevant model for investigating anti-cancer mechanisms.
• Understanding the molecular pathways of apoptosis induction is crucial for developing novel cancer therapies.

Purpose of the Study:

• To elucidate the mechanisms by which Isoliquiritigenin (ISL) induces apoptosis in ovarian carcinoma SKOV-3 cells.
• To investigate the role of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress in ISL-mediated apoptosis.
• To identify key molecular players involved in the signaling pathways triggered by ISL.

Main Methods:

• Cell viability assessed using MTT assay.
• Apoptotic rate determined by flow cytometry with Annexin V-FITC.
• Intracellular ROS, malondialdehyde (MDA), and caspase activities measured using specific assays.
• Western blot analysis performed for ER stress markers (GADD153/CHOP, GRP78, p-eIF2α, ATF6α, XBP1U).

Main Results:

• ISL significantly inhibited SKOV-3 cell proliferation and induced apoptosis.
• ISL treatment increased intracellular ROS and malondialdehyde (MDA) levels.
• ISL triggered endoplasmic reticulum (ER) stress, evidenced by elevated p-eIF2α, GADD153/CHOP, GRP78, and XBP1 expression, and ATF6α cleavage.
• Caspase-12 inhibition partially blocked ROS/MDA formation and ISL-induced apoptosis.

Conclusions:

• Isoliquiritigenin (ISL) induces apoptosis in ovarian carcinoma SKOV-3 cells.
• ISL-induced apoptosis is mediated through the activation of ER stress-signaling pathways.
• The findings support the potential of ISL as a therapeutic agent for ovarian cancer, leveraging ER stress-induced cell death mechanisms.