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Cell Death Induced by the Combination of <i>Ephedra sinica</i> Extract and Radiation in HNSCC is Positively Related to BAX and p-MLKL Expression

[ Vol. 24 , Issue. 1 ]

Author(s):

Seon Rang Woo, Joo Kyung Noh, Sun-Young Ahn, Min Kyeong Lee, Hyeon Seo Yu, Soonki Min, Moonkyoo Kong, Jung Woo Lee, Young Chan Lee, Seong-Gyu Ko and Young-Gyu Eun*   Pages 50 - 57 ( 8 )

Abstract:


<p>Background: Numerous studies have proven the efficacy and safety of natural products, and are widely used as attractive cancer treatments. The investigation of effective natural products for improving cancer treatment is a promising strategy. Combination treatment with radiosensitizers and radiotherapy (RT) is considered necessary for therapeutic improvement in head and neck squamous cell carcinoma(HNSCC). <p> Objective: This study aims to investigate whether Ephedra sinica (ES) extract could induce selective cell death in cancer cells and serve as a radiosensitizer for HNSCC. <p> Methods: HNSCC cells were pretreated with ES extract before radiation, and the radiosensitizing activity was assessed using a colony formation assay. Radiation-induced cell death was evaluated using an annexinV-FITC assay. Western blotting was performed to confirm cell death-related gene expression, including apoptosis and necrosis markers. <p> Results: ES extract significantly inhibited HNSCC cell viability (FaDu and SNU1076), while having minimal effect on normal HaCaT cells. When HNSCC cells were irradiated with 2, 4, or 8 Gy and cultured with ES extract (25 μg/mL), they exhibited increased radiation sensitivity compared to non-treated cells. The combination of ES extract and radiation resulted in increased cell death compared to non-treated, ES-treated, or irradiated cells. The apoptosis marker BAX and necrosis marker p-MLKL expression levels were also elevated following the combination treatment. <p> Conclusion: ES extract demonstrated significant cytotoxic potential in HNSCC cells without affecting normal cells. It enhanced the radiosensitivity of HNSCC cells by upregulating BAX and p-MLKL expression, leading to increased cell death. These results suggest ES extract exhibits a potential radiosensitizing capacity in HNSCC.</p>

Keywords:

Ephedra sinica, head and neck cancer, radiosensitizer, combination therapy, traditional chinese medicine (TCM), TNF&#945;.

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