Radix Tetrastigma Hemsleyani Flavone Suppresses Cutaneous Squamous Cell Carcinoma A431 Cells via Proteasome Inhibition.

Abstract

BACKGROUND Radix Tetrastigma Hemsleyani Flavone (RTHF) has detoxification and anti- inflammation activity and is widely used. Here, we report that RTHF inhibits cell proliferation and induces apoptosis in cutaneous squamous cell carcinoma A431 cells and is a potential strategy for cancer therapy. MATERIAL AND METHODS A431 cells were cultured in different concentrations of RTHF. The inhibition of cell proliferation was assessed by MTT assay, cell apoptosis was shown through FCM, and cell invasion was assessed by Transwell methods. Enzyme proteasome assay was used to detect the activity of proteasome and DUB. Expression of apoptosis-related and ubiquitin proteasome pathway-associated proteins were assessed by PCR and Western blot. RESULTS RTHF obviously suppressed the proliferation and induced apoptosis of A431 cells in a dose-dependent manner. Transwell assay showed that RTHF inhibited the cell metastasis significantly. Enzyme proteasome assay show that the RTHF treatment of activity of proteasome and DUB was significantly lower than in control. RTHF increased the expression of Bax and inhibited Bcl-2, pro-caspase3, and pro-caspase9 activity. The expression of USP14, UCHL5, and POH1 decreased and ub-prs increased significantly in the treatment group. CONCLUSIONS Our study reveals that RTHF-mediated inhibition of DUBs and proteasome may provide a potential strategy for cancer therapy.

• Authors: Liangrui Zhong, Xiaohong Yang, Yiping Zhu, Jianzhong Peng, Yi Cao
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 25 Pg. 436-442 (Jan 15 2019) ISSN: 1643-3750 [Electronic] United States
• PMID: 30643111 (Publication Type: Journal Article)

Chemical References

• BCL2 protein, human
• Drugs, Chinese Herbal
• Flavones
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• Ubiquitin Thiolesterase
• Caspase 3
• Caspase 9
• Proteasome Endopeptidase Complex
• flavone

Topics

• Apoptosis (drug effects)
• Carcinoma, Squamous Cell (pathology)
• Caspase 3 (drug effects)
• Caspase 9 (drug effects)
• Cell Line, Tumor (drug effects)
• Cell Proliferation (drug effects)
• Drugs, Chinese Herbal (therapeutic use)
• Flavones (metabolism, therapeutic use)
• Humans
• Medicine, Chinese Traditional (methods)
• Neoplasm Invasiveness
• Plants, Medicinal (metabolism)
• Proteasome Endopeptidase Complex (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (drug effects)
• Signal Transduction
• Ubiquitin Thiolesterase (metabolism)
• bcl-2-Associated X Protein (drug effects)