Abstract
Retinoblastoma (RB) is one of the most common intraocular malignancies in children, which causes vision loss and even threatens life. Eriodictyol is a natural flavonoid with strong anticancer activity. Some studies have shown that eriodictyol exerts anticancer effects in glioma, colon cancer, and lung cancer; however, no studies have reported the anticancer effects of eriodictyol on RB. Therefore, the aim of this study was to investigate the anticancer activity of eriodictyol against the RB Y79 cell line and its potential mechanism of action. Interestingly, we found that eriodictyol inhibited the proliferation, migration, and invasion of Y79 cells in a dose-dependent manner and decreased the expression of MMP-2 and MMP-9 proteins in the cells. In addition, eriodictyol-induced apoptosis in Y79 cells was assessed by flow cytometry and immunoblotting. Here, our study revealed that eriodictyol dose dependently inhibited the activation of the PI3K/Akt signaling pathway. Notably, the effect of eriodictyol on RB apoptosis was reversed by a PI3K agonist 740 Y-P. In conclusion, our study shows that eriodictyol effectively inhibits proliferation, migration, and invasion and induces apoptosis in RB cell lines, which may be the result of blocking the PI3K/Akt signaling pathway. Thus, eriodictyol may provide a new theoretical basis for exploring targeted antitumor natural therapies.
Highlights
Retinoblastoma (Rb) is one of the most common intraocular malignancies in children due to mutations in the oncogene RB1, which accounts for approximately 4% of all pediatric malignancies [1, 2]
Recent studies have found that Saccharomyces cerevisiae can inhibit glioma cell proliferation and metastasis and induce apoptosis through the PI3K/Akt signaling pathway [9] in addition to its strong anticancer activity in lung, nasopharyngeal, and colon cancers [10,11,12,13,14]
Anti-β-actin, Akt, P-Akt, PI3K, caspase-3, matrix metalloproteinases (MMPs)-2, and matrix metalloproteinase-9 (MMP-9) antibodies were purchased from Abcam (Shanghai, China)
Summary
Retinoblastoma (Rb) is one of the most common intraocular malignancies in children due to mutations in the oncogene RB1, which accounts for approximately 4% of all pediatric malignancies [1, 2]. Protection of the ocular body, improvement of visual acuity, and prevention of metastatic disease are the main treatments for RB. Chemotherapy (intravenous, intra-arterial, and intraocular), local therapies (cryotherapy and transpupillary thermotherapy), radiotherapy (external radiation radiotherapy and plaque radiotherapy), and global extraction are commonly used in clinical practice [3]. Numerous treatment options can improve the survival rate of RB patients, the efficacy is often affected by the duration of the disease, developmental limitations of the economic situation in different countries, drug resistance, and drug side effects. As the research on eriodictyol has intensified, more and more researchers have found that it has various pharmacological activities such as antioxidant, anti-inflammatory, metabolic modulation, and neuroprotection [5,6,7,8]. Recent studies have found that Saccharomyces cerevisiae can inhibit glioma cell proliferation and metastasis and induce apoptosis through the PI3K/Akt signaling pathway [9] in addition to its strong anticancer activity in lung, nasopharyngeal, and colon cancers [10,11,12,13,14]
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