Ovarian cancer is one of the most serious female
malignancies worldwide. Despite intensive efforts being made to overcome
ovarian cancer, there still remain limited optional treatments for this disease.
Nobiletin, a prospective food-derived
phytochemical extracted from citrus fruits, has recently been reported to suppress
ovarian cancer cells, but the role of pyroptosis in ovarian
carcinoma with
nobiletin still remains unknown. In this study, we aim to explore the effect of
nobiletin on ovarian
carcinoma and further expound the underlying mechanisms of
nobiletin-induced
ovarian cancer cell death. Our results showed that
nobiletin could significantly inhibit cell proliferation, induce DNA damage, and also lead to apoptosis by increasing the cleaved
poly (ADP-ribose) polymerase (PARP) level of human
ovarian cancer cells (HOCCs) in a dose-dependent manner. Moreover, we revealed that
nobiletin decreased mitochondrial membrane potential and induced
reactive oxygen species (ROS) generation and autophagy of HOCCs, contributing to gasdermin D-/gasdermin E-mediated pyroptosis. Taken together,
nobiletin as a functional food ingredient represents a promising new anti-
ovarian cancer candidate that could induce apoptosis and trigger ROS-mediated pyroptosis through regulating autophagy in
ovarian cancer cells.