Title:Cell Death Induced by the Combination of Ephedra sinica Extract and Radiation in
HNSCC is Positively Related to BAX and p-MLKL Expression
Volume: 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*
Affiliation:
- Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University School of Medicine, Kyung Hee University Medical
Center, Seoul, Republic of Korea
- Central Laboratory, Medical Science Research Institute, Kyung Hee University Medical Center,
Seoul, Republic of Korea
- Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, Republic
of Korea
Keywords:
Ephedra sinica, head and neck cancer, radiosensitizer, combination therapy, traditional chinese medicine (TCM), TNFα.
Abstract:
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).
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.
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.
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.
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.
