Abstract
In current study, we investigated the anti-tumor effect of luteolin in human ESCC cell lines in vitro and in vivo and tried to explore the potential mechanisms. Results from flow cytometry showed that luteolin could induce apoptosis and caspase-3 activation and induce cell cycle arrest at G2/M phase in a dose- and time-dependent manner in EC1 and KYSE450 cells. JC-1 test results showed that membrane potential of mitochondria after luteolin treatment was down-regulated and this was an indicator for intrinsic apoptosis. Western Blot results showed the expression of cell cycle regulatory protein p21 and p53 increased and three apoptosis related proteins that participate in mitochondrial apoptotic pathway, namely, Bim, CYT-c and cPARP, also increased in luteolin treated cells compared with control groups. We further confirmed that luteolin could significantly inhibit the growth of ESCC tumors in xenograft mouse models and no evidence of systemic toxicity was observed. Our results suggest that luteolin can induce cell apoptosis and cell cycle arrest in G2/M phase through mitochondrial pathway in EC1 and KYSE450 cell lines and proper utilization of luteolin might be a practical approach in ESCC chemotherapy.
Highlights
Esophageal squamous cell carcinoma (ESCC), the predominant histological subtype of esophageal cancer, and it is characterized by high mortality and striking geographic variation throughout the world with the highest incidence rate in east Asia [1, 2]
Our results suggest that luteolin can induce cell apoptosis and cell cycle arrest in G2/M phase through mitochondrial pathway in EC1 and KYSE450 cell lines and proper utilization of luteolin might be a practical approach in ESCC chemotherapy
Several studies have demonstrated that luteolin could induce cell cycle arrest and further inhibit proliferation and induce apoptosis in different types of cancer cells in vitro, including cell lines from hepatocellular carcinoma, cholangiocarcinoma, leukemia, thyroid cancer, breast cancer, prostate cancer, melanoma, lung cancer, oral squamous cancer, stomach cancer, gastric cancer, colon cancer, as well as ESCC and EAC [9, 17,18,19, 26,27,28,29,30,31,32,33,34,35,36,37]
Summary
Esophageal squamous cell carcinoma (ESCC), the predominant histological subtype of esophageal cancer, and it is characterized by high mortality and striking geographic variation throughout the world with the highest incidence rate in east Asia [1, 2]. Surgical resection is curative only at an early stage in ESCC and chemoradiotherapy is recommended for majority of patients with advanced esophageal cancer [5,6,7]. Traditional chemotherapy drugs, such as cisplatin, carboplatin, have certain effects on ESCC, at the same time the regimen have a high incidence of side effects, such as mucositis and leukocytopenia, as well as treatment-related death (16%) [8]. It is important to find chemotherapeutic agents with higher specificity, efficacy and fewer side effects for ESCC
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