Huaier Inhibits Proliferation, Migration, and Invasion of Cutaneous Squamous Cell Carcinoma Cells by Inhibiting the Methylation Levels of CDKN2A and TP53

Abstract

Cutaneous squamous cell carcinoma (CSCC) is a malignant tumor that originates from keratinocytes in the epidermis or appendage. Traditional Chinese medicine Huaier has anti-tumor activity in various malignancies. Little is known about the role of Huaier in CSCC. Here, we investigated the function of Huaier in CSCC. We treated CSCC cell line (SCL-1 and A431) with a series of concentration gradients of Huaier to examine the half maximal inhibitory concentration (IC50) of Huaier on SCL-1 and A431 cells. The IC50 of Huaier on growth of SCL-1 and A431 cells were 6.96 and 7.57 mg/mL, respectively. Moreover, Huaier reduced the methylation levels of CDKN2A and TP53, and enhanced the expression of CDKN2A and TP53 in SCL-1 and A431 cells in a dosage-dependent manner. The expression of DNA methyltransferase DNMT1 was severely repressed by Huaier treatment in SCL-1 and A431 cells. DNMT1 overexpression enhanced the methylation levels of CDKN2A and TP53, and suppressed the expression of CDKN2A and TP53 in Huaier-treated SCL-1 and A431 cells. Huaier treatment inhibited proliferation, migration, and invasion of SCL-1 and A431 cells. However, inhibition of CDKN2A or TP53 reversed the influence of Huaier treatment on proliferation, migration, and invasion of CSCC cells. In conclusion, our data demonstrate that Huaier inhibits proliferation, migration, and invasion of CSCC cells by regulating DNA methylation of CDKN2A and TP53, thereby attenuating the progression of CSCC. Thus, Huaier extract may act as a drug for treating CSCC.

A network pharmacology-based exploration of the active compounds and potential drug targets of Si-Jun-Zi decoction in the treatment of cutaneous squamous cell carcinoma

“…In recent years, there are a number of reported results show that SJZ decoction or SJZ based Chinese traditional medicine in the bladder cancer mice, lung cancer mice that accept chemotherapy have enhanced the effect of chemotherapy drugs, reduce the effect of chemotherapy drugs toxic side effects through inhibiting tumor growth and can prolong the survival of mice (17,18). In addition to gastric cancer (19)(20)(21)(22), it has also been studied at an animal level or cellular level in the clinical treatment of HOSCC and multiple types of lung cancer (23), but we did not find any previous studies related to SJZ in cSCC.…”

Necroptosis-related genes are associated with prognostic features of kidney renal clear cell carcinoma

“…CDKN2A mutation is very common in tumors. Its mutations mainly include homozygous deletion, mutation and promoter abnormal methylation of p16INK4a / p14ARF gene [ 47 ]. ZBP1 was originally found as an up-regulated gene in the transcriptome study of tumor cells by interferon and named DLM-1.…”

A logic “OR” gate composed of a blue light‐induced CRISPR/dCas9 system and a Tet‐on system activates cancer suppressor genes to inhibit the growth of cutaneous squamous cell carcinoma cells

“…[30,31] In this work, we established an "OR" logic gate based on CRISPR-Cas9 in cSCC cells with a blue light induction system and tetracycline induction system, and selected CDH1 and p53 genes as effector genes of the two systems. [32][33][34] The expression of p53 protein or E-cadherin would increase when the logic gate was exposed to blue light irradiation and Dox. These results indicate that, when the transfected tumour cells were exposed to the above two conditions, the ability of cells' proliferation, migration and invasion were inhibited, and the apoptosis rate would increase.…”