A novel cell cycle blocker extracted from Stellera chamaejasme L. inhibits the proliferation of hepatocarcinoma cells

Abstract

Abstract. Currently, liver cancer is the sixth most prevalent cancer and the third most common cause of cancer-related death. However, effective chemotherapeutic drugs with low drug resistance and few side-effects for the clinical treatment of liver cancer are lacking. Therefore, the search for novel drugs to compensate for the defects of existing drugs is urgently needed. Herein, we successfully screened an extract named from Stellera chamaejasme L. (SCL), a historically confimed antitumor plant, through a novel extraction platform. In the present study, we firstly screened the anticancer effect of ESC by the sulforhodamine B (SRB) cell proliferation assay in a wide range of malignant cell lines, including A549, NCI-H157, NCI-H460, SK-HEP-1 and HepG2. With the highest inhibitory rate in hepatocarcinoma cells, we further identified the tumor-suppressive efficacy and the safety of ESC in an H22 hepatocarcinoma xenograft model in vivo. In a mechanistic study, flow cytometry and western blot analysis were performed to evaluate the effects of ESC on the induction of cell apoptosis, intervention of cell cycle distribution and its influence on key G2/M-phase regulators. The results showed that ESC significantly inhibited the cell growth of liver cancer cell lines. Accordingly, the tumor inhibition rate was also increased following ESC administration with little systemic toxicity in H22-transplanted mice. Mechanistically, ESC caused obvious G2/M-phase arrest in both the SK-HEP-1 and HepG2 cell lines without cell apoptosis. Furthermore, cyclin B1 was downregulated, while the phosphorylation level of CDK1 was increased in response to ESC treatment. All these data confirmed that ESC possesses potent anti-proliferative efficacy for hepatocarcinoma through the induction of cyclinmediated cell cycle arrest. Thus, ESC is a promising candidate for hepatocarcinoma treatment in the future. IntroductionAs one of the major global public health issues, cancer greatly threatens human survival and has become the leading cause of mortality of humankind in this century (1). Clinically, during the rapid development of anticancer strategies, chemotherapy has consistently played an important role in cancer treatment. To date, classical botanical agents, as represented by paclitaxel or vincristine, are still first-line drugs and are widely applied as the primary choice against multiple malignancies (2). Benefitting from these agents, treatment effectiveness and the survival rate of cancer patients have greatly improved in recent years. However, in spite of the satisfactory tumor-suppressive activities, with their extensive application worldwide, growing evidence reveals that side-effects and drug resistance are still the leading obstacles largely limiting the clinical use of classic tumor-toxic agents (3).In recent years, liver cancer has become one of the most prevalent types of cancer and is the third most common cause of cancer-related mortality (4,5). Notably, its incidence and mortality rank second among Chinese cancer patients (6) an...

Extract of Stellera Chamaejasme L. Inhibits the Progression of Hepatocellular Carcinoma by Regulating miR-134-5p and JAK1/STAT3 Pathway

“…ESC is widely utilized in traditional Chinese medicine and confirmed to possess antibacterial, 24 antivirus, 25 and antitumors activities. 6,7 To explore the effects of ESC on HCC progression, the authors first detected its cytotoxicity to HCC cells and found that ESC inhibited cell proliferation in a dose-and time-dependent manner, and cell sur-vival rate had a sharp downtrend at 20 lg/mL ESC. They then chose this concentration for the next experiments.…”

“…6 Kan et al reported that ESC inhibited the proliferation of HCC cells. 7 Another article showed that ESC repressed metastasis of HCC cells. 8 However, the mechanism of ESC in modulating HCC progression is still unclear and needs to be further studied.…”

Ethanol extract of Patrinia scabiosaefolia induces the death of human renal cell carcinoma 786-O cells via SIRT-1 and mTOR signaling-mediated metabolic disruptions

“…Traditional Chinese medicine (TCM), including various natural plant extracts, has shown tremendous potential for the discovery of alternative drugs for the treatment of cancer (1,2). Fewer adverse effects and cost effectiveness endow TCM great advantages over Western chemotherapeutics (3).…”

A novel anti-metastatic extract from Stellera chamaejasme Linn. suppresses breast tumor cell motility through inhibition of focal adhesion kinase

“…Specifically, the efficacy of low-dose ESC was first identified in two BALB/c tumor mouse models (0.10 mg/kg or 1.00 mg/kg, which were 1/1000 or 1/100 of the doses commonly used in previous studies [5] ). In the subcutaneous xenograft tumor model, in line with our hypothesis, 0.10 mg/kg or 1.00 mg/kg ESC showed a minimal influence on the living conditions and body weight of mice compared with the negative control [Supplementary Figure 1A, http://links.lww.com/CM9/B270].…”

“…Inspired by the in vivo results, we further explored the potential association of ESC with cell motility regulation. The commonly used dosage of ESC is 20 to 100 μg/mL in vitro [5] . In this study, we screened the safety of different ESC doses using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, ranging from 1.56 to 25.00 μg/mL.…”