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Scutellarein Induces Apoptosis in SCC-25 Oral Squamous Cell Carcinoma Cells Through Suppression of the PI3K/Akt
Shiao Cheng-Kai1,2, Chan-Chiung Liu2, Yingxiao Li3
1Department of Chest Medicine, Kaohsiung Veterans General Hospital Tainan Branch, Tainan, Taiwan, R.O.C.
Background/Aim:
Oral squamous cell carcinoma (OSCC) remains a major global health burden with poor long-term survival, highlighting the need for novel therapeutic agents. This study aimed to evaluate the anticancer potential of scutellarein and to elucidate its underlying mechanisms in OSCC cells.
Materials And Methods:
The OSCC cell line SCC-25 and normal oral fibroblasts (OFs) were used in this study. Morphological assessment, MTT, ELISA, JC-1 staining, and immunoblotting assays were performed to evaluate membrane blebbing, cell viability, cytokeratin-18 fragment release, changes in mitochondrial membrane potential (MMP), and protein expression, respectively. In addition, PI3Kinase catalytic subunit alpha (PIK3CA) overexpression was used to examine the involvement of the PI3K/Akt pathway in the effects mediated by scutellarein.
Results:
Scutellarein preferentially reduced SCC-25 cell viability, with IC50 values of 25.6 μM in SCC-25 cells and 206.6 μM in OFs, indicating tumor-selective cytotoxicity. Scutellarein induced apoptosis in SCC-25 cells, as evidenced by increased membrane blebbing, elevated levels of cleaved poly(ADP-ribose) polymerase, and enhanced release of cytokeratin-18 fragments. Mechanistically, scutellarein upregulated Fas, disrupted MMP, and increased the levels of cleaved caspase-8, caspase-9, and caspase-3. Scutellarein also suppressed phosphoinositide 3-kinase (PI3K)/Akt phosphorylation. Importantly, PIK3CA overexpression increased Akt phosphorylation and attenuated scutellarein-induced cytokeratin-18 fragment release and caspase cascade activation, further supporting the involvement of PI3K/Akt inhibition in the anticancer effects of scutellarein.
Conclusion:
Scutellarein exerts tumor-selective cytotoxic and pro-apoptotic effects in SCC-25 cells, at least in part, by suppressing the PI3K/Akt pathway.
Insights
Scutellarein demonstrates tumor-selective anticancer effects against oral squamous cell carcinoma (OSCC) by inducing apoptosis and inhibiting the PI3K/Akt pathway. This natural compound offers potential as a novel therapeutic agent for OSCC.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Oral squamous cell carcinoma (OSCC) presents a significant global health challenge with limited treatment options and poor patient outcomes.
- The urgent need for novel therapeutic strategies necessitates the investigation of natural compounds with anticancer properties.
Purpose of the Study:
- To evaluate the anticancer potential of scutellarein in OSCC cells.
- To elucidate the molecular mechanisms underlying scutellarein's effects in OSCC.
Main Methods:
- Utilized the OSCC cell line SCC-25 and normal oral fibroblasts (OFs).
- Assessed cell viability (MTT), apoptosis (membrane blebbing, cleaved PARP, caspase activation), mitochondrial membrane potential (JC-1 staining), and protein expression (ELISA, immunoblotting).
- Investigated the role of the PI3K/Akt pathway using PIK3CA overexpression.
Main Results:
- Scutellarein exhibited significant tumor-selective cytotoxicity against SCC-25 cells (IC50 = 25.6 μM) compared to OFs (IC50 = 206.6 μM).
- Scutellarein induced apoptosis via upregulation of Fas, disruption of mitochondrial membrane potential, and activation of the caspase cascade (caspase-8, -9, -3).
- Scutellarein suppressed PI3K/Akt signaling, and PIK3CA overexpression attenuated scutellarein's pro-apoptotic effects, confirming pathway involvement.
Conclusions:
- Scutellarein possesses tumor-selective cytotoxic and pro-apoptotic properties against OSCC cells.
- The anticancer effects of scutellarein are mediated, in part, by the suppression of the PI3K/Akt signaling pathway.
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