Molecular Mechanisms Underlying the Anticancer Activity of Chrysin Through p53 Tumor Suppressor in HepG2 Cell Lines
Abstract:
Chrysin,
a natural flavonoid found in passionflower, honey, and propolis, is gaining
attention for its antioxidant, anti-inflammatory, and anticancer properties.
This study evaluates chrysin’s anticancer efficacy against HepG2 liver cancer
cells. We assessed its antioxidant potential using DPPH and nitric oxide
scavenging assays, which revealed significant, concentration-dependent radical
scavenging activity, emphasizing chrysin’s strong antioxidant properties. These
effects are likely to reduce oxidative stress, a factor that promotes cancer
cell proliferation and survival. Cytotoxicity was measured with the MTT assay,
and gene expression analysis through RT-qPCR showed that chrysin upregulated
pro-apoptotic genes such as Bax, Caspase 3, and Caspase 9, while downregulating
the anti-apoptotic gene Bcl-2. Notably, chrysin also increased the expression
of the tumor suppressor gene p53, essential for cell cycle regulation and
apoptosis in response to stress and DNA damage. Molecular docking studies were
performed to investigate chrysin’s interactions with key apoptotic proteins.
The docking results showed strong binding affinities between chrysin and Bax,
Bcl-2, Caspase 3, Caspase 9, and p53. Particularly high binding affinities with
Caspase 9 and p53 suggest that chrysin may effectively trigger the intrinsic
apoptotic pathway, leading to cancer cell death. The interaction with p53 is
significant as it may stabilize and activate p53, enhancing the transcription
of pro-apoptotic genes. These findings highlight chrysin's potential as a
therapeutic agent for liver cancer, primarily through the p53-mediated
apoptotic pathway. While these in vitro results are promising, further in vivo
studies and clinical trials are necessary to confirm chrysin’s efficacy and
safety in a clinical setting.
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