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PP-77

Molecular insights into the anti-metastatic and metabolic regulatory effects

of timosaponin AIII in endometrial cancer

,2
1
Yi-Chen Lai, Chia-Liang Lin*

1 Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan
2 Department of Biochemistry, School of Medicine, Chung Shan Medical University,
Taichung, Taiwan
* E-mail: t03742@csmu.edu.tw

Abstract
Over the past four decades, malignant tumors have remained the leading cause of death in
Taiwan, with the incidence and mortality of endometrial cancer steadily increasing among
women. This trend underscores the urgent need for novel therapeutic strategies with enhanced
efficacy and reduced toxicity. Timosaponin AIII (TSAIII), a steroidal saponin isolated from
Anemarrhena asphodeloides, has been reported to exert antitumor, anti-inflammatory, and
antioxidant activities; however, its effects in endometrial cancer remain poorly characterized.
In this study, we investigated the potential anticancer activities of TSAIII in endometrial cancer
cells. MTT assays demonstrated that TSAIII exerted dose-dependent cytotoxicity above 6 μM,
while non-cytotoxic concentrations did not significantly affect the cell cycle distribution of
Hec151 and AN3CA cells. Importantly, Boyden chamber assays revealed that TSAIII markedly
suppressed cell migration and invasion. Seahorse bioenergetic profiling further showed that
TSAIII significantly impaired mitochondrial oxidative phosphorylation without affecting
glycolysis, suggesting a mitochondria-centered regulatory mechanism. In addition, qPCR
analysis indicated that TSAIII downregulated the expression of the immune checkpoint
molecule PD-L1, implying a reduced immunosuppressive capacity of tumor cells. Collectively,
these findings provide preliminary evidence that TSAIII inhibits metastatic potential,
reprograms mitochondrial energy metabolism, and suppresses PD-L1 expression in endometrial
cancer cells. These results highlight TSAIII as a promising therapeutic candidate and warrant
further investigation into its molecular mechanisms within the tumor microenvironment.

Keywords: Timosaponin AIII (TSAIII); Endometrial Cancer; Metastasis; Mitochondrial Energy
Metabolism; PD-L1