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Published on: January 12, 2020
BCL2L1 is identified as a target of naringenin in regulating ovarian cancer progression
Jing Xu1, Zhe Guo2, Shuang Yuan2
1Department of Obstetrics and Gynecology, Nanyang Central Hospital, No. 312 Gongnong Road, Nanyang, 473005, China. xjfkybq@163.com.
Abstract:
Naringenin is a natural bioactive flavonoid with a wide spectrum of biological activities, including anti-carcinogenic ability. Our study aimed to investigate the effect of naringenin on ovarian cancer (OC) progression. Naringenin was input into PharmMapper and SwissTargetPrediction databases to predict its targets, and OC-related targets were obtained using MalaCards and GEPIA databases, which were imported into online Venn tool to identify the common targets. B-cell lymphoma-2 like 1 (BCL2L1) expression in OC tissues and cells was detected using GEPIA and HPA databases, qRT-PCR and Western blot analysis. The prognostic and diagnostic values of BCL2L1 in OC were determined using Kaplan-Meier plotter tool and receiver operating characteristic (ROC) curve analysis, respectively. Cell proliferation was evaluated using CCK-8 and EdU incorporation assays. Cell apoptosis was determined using TUNEL and caspase-3 activity assays. Effect of naringenin on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway was evaluated by Western blot analysis. BCL2L1 was identified as the candidate target of naringenin against OC. BCL2L1 was upregulated in OC tissues and cells. Naringenin decreased BCL2L1 expression and inactivated the PI3K/Akt pathway in OC cells. Naringenin inhibited cell proliferation and increased the apoptotic rate in OC cells, while these effects were partially abolished by BCL2L1 overexpression and treatment with 740Y-P, a PI3K activator. In conclusion, naringenin exerted an anti-tumor effect on OC progression via inactivation of the PI3K/Akt/BCL2L1 pathway.
Insights
Naringenin, a natural flavonoid, combats ovarian cancer (OC) by targeting B-cell lymphoma-2 like 1 (BCL2L1). This compound inhibits OC cell proliferation and promotes apoptosis by inactivating the PI3K/Akt/BCL2L1 pathway.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Naringenin is a natural flavonoid with known anti-carcinogenic properties.
- Ovarian cancer (OC) remains a significant health concern requiring novel therapeutic strategies.
Purpose of the Study:
- To investigate the anti-tumor effects of naringenin on ovarian cancer progression.
- To identify the molecular targets and pathways involved in naringenin's action against OC.
Main Methods:
- Bioinformatic analyses (PharmMapper, SwissTargetPrediction, MalaCards, GEPIA) were used to predict and identify naringenin's targets in OC.
- Quantitative real-time PCR (qRT-PCR) and Western blot analysis were employed to assess B-cell lymphoma-2 like 1 (BCL2L1) expression.
- Cell proliferation, apoptosis, and pathway activation assays (CCK-8, EdU, TUNEL, caspase-3, Western blot) were conducted.
Main Results:
- B-cell lymphoma-2 like 1 (BCL2L1) was identified as a key target of naringenin in ovarian cancer.
- BCL2L1 expression was found to be upregulated in OC tissues and cells.
- Naringenin treatment decreased BCL2L1 expression, inhibited cell proliferation, and induced apoptosis in OC cells by inactivating the PI3K/Akt pathway.
Conclusions:
- Naringenin demonstrates significant anti-tumor activity against ovarian cancer.
- The anti-cancer effects of naringenin are mediated through the downregulation of BCL2L1 and the inactivation of the PI3K/Akt pathway.
- Naringenin represents a potential therapeutic agent for ovarian cancer treatment.
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