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

Abstract

BackgroundRadix 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/MethodsA431 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.ResultsRTHF 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.ConclusionsOur study reveals that RTHF-mediated inhibition of DUBs and proteasome may provide a potential strategy for cancer therapy.

UPLC-Q-TOF-MSE Based Profiling of the Chemical Composition of Different Parts of Tetrastigma hemsleyanum

“…According to the report, the main components of T. hemsleyanum extract are flavonoids, polysaccharides, and phenolic acids. Modern pharmacological studies have confirmed that the effective pharmacodynamic components of antitumor effect in T. hemsleyanum are mainly flavonoids, 19,20 flavonoids have a variety of pharmacological activities. 21–23 Studies have shown that flavonoids constitute a significant proportion of the active ingredients in T. hemsleyanum , and they have been a focal point in the investigation of the plant's chemical constituents in recent years.…”

The Phytochemistry, Pharmacology, and Quality Control of Tetrastigma hemsleyanum Diels & Gilg in China: A Review

“…In the in vitro experiments with different lung cancer cells (A549 cells and A431 cells), the total flavonoids of TDG can inhibit the proliferation and apoptosis of tumor cells, and its mechanism of action involves the Bcl-2 family proteins, Caspase family proteins, MAPK pathway, and the ubiquitin-proteasome pathway. Besides, the total flavonoids of TDG can markedly inhibit the metastasis and invasion of tumor cells, with migration and invasion being associated with the activation of MMPs and TIMPs proteins (Zhong et al, 2013;Zhong et al, 2016;Zhong et al, 2017;Zhong et al, 2019). The above studies indicate that the total flavonoids of TDG has a very good therapeutic effect on lung cancer at the cellular level.…”

Investigating Cutaneous Squamous Cell Carcinoma in vitro and in vivo: Novel 3D Tools and Animal Models

“…The pioneering work of Giard and collaborators ( 65 ), back in 1973, allow the establishment of 13 tumor cell lines, starting from more than 200 different tumor types, including carcinomas, sarcoma, melanoma, and brain neoplasms. From this work, the epidermoid carcinoma cell line A-431, derived from an 85-year-old female, started, and kept being used for experiments related to cSCC ( 66 – 68 ). Similarly, the epithelial cell line DJM-1, specifically derived from a malignant trichilemmal cyst cell, from an 87-years-old Japanese female ( 69 ), is considered as a good model for cSCC ( 70 – 73 ).…”