Esculetin has therapeutic potential via the proapoptotic signaling pathway in A253 human submandibular salivary gland tumor cells

Park,Su-Bin; Jung,Woo Kwon; Kim,Hyung Rae; Yu,Hwa-Young; Kim,Yong Hwan; Kim,Junghyun

doi:10.3892/etm.2022.11460

Esculetin has therapeutic potential via the proapoptotic signaling pathway in A253 human submandibular salivary gland tumor cells

Authors:
- Su-Bin Park
- Woo Kwon Jung
- Hyung Rae Kim
- Hwa-Young Yu
- Yong Hwan Kim
- Junghyun Kim
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Affiliations: Department of Oral Pathology, School of Dentistry, Jeonbuk National University, Jeonju, Jeollabuk-do 54896, Republic of Korea
Published online on: June 22, 2022 https://doi.org/10.3892/etm.2022.11460
Article Number: 533
Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Esculetin is a natural lactone that is commonly derived from coumarins. According to previous experiments using human cancer cells, esculetin has potent antitumor activity; it also inhibits proliferation and induces the apoptosis of cancer cells. In the present study, the anti‑proliferative effect of esculetin on the submandibular salivary gland tumor cell line, A253, was evaluated via in vitro and in vivo analyses. Furthermore, the anti‑cancer effects of esculetin in A253 cells and a xenograft model of salivary gland tumors were determined using 3‑(4,5‑dimethylthiazol)‑2,5‑diphenyltetrazolium bromide and TUNEL assay, apoptosis protein array, quantitative polymerase chain reaction and western blot analysis. Esculetin (50‑150 µM) was demonstrated to have an anti‑proliferative effect in the A253 cell line in vitro; this observed effect was dependent on the dose and duration of treatment. Esculetin also increased the levels of Bax, cleaved caspase‑3, cleaved‑9 and cleaved poly (ADP‑ribose) polymerase apoptosis‑related proteins, and decreased the expression levels of the Bcl‑2 anti‑apoptotic protein. With respect to apoptosis regulation, esculetin significantly decreased the proliferation of tumor cells in a xenograft model (100 mg/kg/day) for 18 days. Overall, esculetin could be a potential oral anticancer drug against salivary gland cancer.

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