18β-glycyrrhetinic Acid Modulated Autophagy is Cytotoxic to Breast Cancer Cells

Hsu, Yu-Chih; Hsieh, Wen-Che; Chen, Shu-Hsin; Li, Yi-Zhen; Liao, Hui-Fen; Lin, Mei-Yi; Sheu, Shew-Meei

doi:10.7150/ijms.80302

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International Journal of Biological Sciences

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Int J Med Sci 2023; 20(4):444-454. doi:10.7150/ijms.80302 This issue Cite

Research Paper

18β-glycyrrhetinic Acid Modulated Autophagy is Cytotoxic to Breast Cancer Cells

Yu-Chih Hsu^1,2*, Wen-Che Hsieh^1*, Shu-Hsin Chen³, Yi-Zhen Li³, Hui-Fen Liao⁴, Mei-Yi Lin^1,5✉, Shew-Meei Sheu^3✉

1. Department of Chinese Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi City 60002, Taiwan
2. Department of Chinese Medicine, China Medical University Hospital, Taichung City 40447, Taiwan
3. Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi City 60002, Taiwan
4. Department of Biochemical Science and Technology, National Chiayi University, Chia-Yi City 60004, Taiwan
5. Department of Food Nutrition and Health Biotechnology, Asian University, Taichung City 41354, Taiwan
*Contributed equally

Citation:

Hsu YC, Hsieh WC, Chen SH, Li YZ, Liao HF, Lin MY, Sheu SM. 18β-glycyrrhetinic Acid Modulated Autophagy is Cytotoxic to Breast Cancer Cells. Int J Med Sci 2023; 20(4):444-454. doi:10.7150/ijms.80302. https://www.medsci.org/v20p0444.htm

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Abstract

The development of endocrine therapy resistance in the luminal A subtype of breast cancer is related to the appearance of protective autophagy. The bioactive component from the root of licorice, 18β-glycyrrhetinic acid (18β-GA), has many antitumor properties. Whether 18β-GA can modulate autophagy to inhibit proliferation of the luminal A subtype is still unclear. The proportion of apoptosis caused by 18β-GA in MCF-7 and T-47D cells was determined using flow cytometry. The autophagy marker, LC3-II conversion, was investigated using Western blotting, and a Premo^TM Tandem Autophagy Sensor Kit. We found that the concentration (150-μM) of 18β-GA caused caspase-dependent apoptosis and LC3-II accumulation or blocked autophagic flux. Moreover, 18β-GA-mediated apoptosis was improved using rapamycin but reversed by 3-methyladenine (3-MA) addition. The phosphorylation level of Jun-amino-terminal kinase (JNK) was increased significantly in the 18β-GA treatment and combined incubation using rapamycin. A JNK inhibitor (SP600125) significantly inhibited 18β-GA-mediated apoptosis, LC3-II accumulation and rescued the numbers of MCF-7 and T-47D colony formation. Especially, 18β-GA can inhibit xenograft tumor growth in BALB/c nude mice. These data indicate the combination of 18β-GA with rapamycin or 3-MA can sensitize or decrease MCF-7 and T-47D cells to 18β-GA-induced apoptosis, respectively. 18β-GA modulated autophagy is cytotoxic to luminal A subtype breast cancer cells through apoptosis promotion and JNK activation.

Keywords: 18β-glycyrrhetinic acid, autophagy, apoptosis

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APA

Hsu, Y.C., Hsieh, W.C., Chen, S.H., Li, Y.Z., Liao, H.F., Lin, M.Y., Sheu, S.M. (2023). 18β-glycyrrhetinic Acid Modulated Autophagy is Cytotoxic to Breast Cancer Cells. International Journal of Medical Sciences, 20(4), 444-454. https://doi.org/10.7150/ijms.80302.

ACS

Hsu, Y.C.; Hsieh, W.C.; Chen, S.H.; Li, Y.Z.; Liao, H.F.; Lin, M.Y.; Sheu, S.M. 18β-glycyrrhetinic Acid Modulated Autophagy is Cytotoxic to Breast Cancer Cells. Int. J. Med. Sci. 2023, 20 (4), 444-454. DOI: 10.7150/ijms.80302.

NLM

CSE

Hsu YC, Hsieh WC, Chen SH, Li YZ, Liao HF, Lin MY, Sheu SM. 2023. 18β-glycyrrhetinic Acid Modulated Autophagy is Cytotoxic to Breast Cancer Cells. Int J Med Sci. 20(4):444-454.

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