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

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, Young-Gyu Eun

Anti-cancer agents in medicinal chemistry 2024

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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). 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. 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. 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. 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. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Citation

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, Young-Gyu Eun. Cell Death Induced by the Combination of Ephedra sinica Extract and Radiation in HNSCC is Positively Related to BAX and p-MLKL Expression. Anti-cancer agents in medicinal chemistry. 2024;24(1):50-57