Open Access

ARTICLE

Anticancer effects of SH003 and its active component Cucurbitacin D on oral cancer cell lines via modulation of EMT and cell viability

HYEONG SIM CHOI¹, JEONG-KUI KU¹, SEONG-GYU KO², PIL-YOUNG YUN^1,3,*

1 Department of Oral and Maxillofacial Surgery, Section of Dentistry, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea
2 Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, 02435, Republic of Korea
3 Department of Dentistry and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, 03080, Republic of Korea

* Corresponding Author: PIL-YOUNG YUN. Email:

Oncology Research 2025, 33(5), 1217-1227. https://doi.org/10.32604/or.2025.059791

Received 17 October 2024; Accepted 03 January 2025; Issue published 18 April 2025

Abstract

Background: Oral cancer remains a significant global health challenge, as it has high morbidity and mortality rates. Current treatments show limited efficacy and have severe side effects, prompting searches for new therapeutic agents. SH003, a traditional herbal formulation comprising Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii, has demonstrated potential anticancer properties in previous studies. However, its specific efficacy against oral cancer and the role of its key components, particularly Cucurbitacin D, remain underexplored. Methods: The cytotoxic effects of SH003 and its major components—i.e., Cucurbitacin D, Decursin, Formononetin, and Nodakenin—were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), Trypan Blue exclusion, and Lactate Dehydrogenase (LDH) release assays. Cell migration was analyzed via wound healing assays, and apoptosis induction was assessed using cell cycle analysis and caspase activation assays. Epithelial-to-mesenchymal transition (EMT) marker expression (E-cadherin and N-cadherin) was measured using Western blotting and Quantitative reverse transcription PCR (qRT-PCR). Results: SH003 significantly reduced cell viability in a dose-dependent manner, with YD-8 and YD-9 cells showing greater sensitivity than YD-38 cells. Of the individual compounds, Cucurbitacin D was identified as a key active agent, as it exhibited potent inhibition of cell migration and significant modulation of EMT markers, including the upregulation of E-cadherin and downregulation of N-cadherin. These effects were most pronounced in YD-9 cells. Conclusions: Taken together, these findings suggest that Cucurbitacin D plays a crucial role mediating the anticancer activity of SH003, particularly via the reversal of EMT and the reduction of migratory and invasive potential of oral cancer cells. This study provides valuable insight into the mechanistic basis of SH003, highlighting its potential as a therapeutic agent against oral cancer. Further research, including in vivo studies and clinical trials, is needed to elucidate its precise mechanisms and potential applications against other cancer types.

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Keywords

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