TMF, a natural dihydroflavonoid isolated from Scutellaria javanica Jungh, stimulates anticancer activity of s180 cancer-bearing mice, induces apoptosis, inhibits invasion and migration on HepG-2 cells

Abstract

Ethnopharmacological relevance5-hydroxy-7,8,2′,6′-tetramethoxy flavanone (TMF) is a dihydroflavonoid extracted from Scutellaria javanica Jungh. It is a species of genus Scutellaria, and a representative southern herb and Li nationality medicine. The plant has been used as an ethnic medicine in treating cancer and the main components are dihydroflavonoids. However, the underlying mechanisms are yet to be elucidated. Aim of the studyThe present study aimed at investigating the efficacy of TMF in cancer and the underlying mechanisms. Materials and methodsThe s180 cancer-bearing mice experiment in vivo was designed to study the tumor growth inhibition of TMF. Also, we investigated the latent mechanism of TMF induced apoptosis and the inhibitory action of TMF on the metastasis and proliferation in HepG-2 cells. The in vitro experimental groups were treated with TMF or hydroxycamptothecine (HCPT) for 24 h. Apoptosis was detected by flow cytometry. Caspase-3 activity was detected by ELISA. The expressions of PCNA, Bcl-2, Bax, p53, E-Cadherin, MMP-9, MMP-2, STAT3, p-STAT3, JAK2, p-JAK2, AKT, p-AKT, ERK1/2 and p-ERK1/2 were examined by Western blot. ResultsAfter oral administration of TMF in s180 cancer-bearing mice, tumor growth in vivo was suppressed significantly. The MTT assay result and the reduction of PCAN proved that TMF could inhibit HepG-2 cells proliferation. TMF also caused dose-dependent apoptosis on HepG-2 cells. The experimental results showed that the expression of Bcl-2 was reduced, and the expressions of caspase-3, Bax and p53 were increased. Therefore, we speculated that TMF-induced apoptosis might be achieved by regulating the p53-Bcl-2/Bax-caspase-3 pathways. Transwell cell migration and invasion assay showed that treatment with TMF inhibited the invasion and migration in HepG-2 cells. The expressions of MMP-9 and MMP-2 were decreased while that of E-cadherin was enhanced significantly by TMF. Additionally, the expressions of p-JAK2, p-STAT3, p-AKT and p-ERK1/2 were decreased, but those of JAK2, STAT3, AKT and ERK1/2 remained unchanged. Thus, it is indicated that TMF induced apoptosis and inhibited proliferation and metastasis on HepG-2 cells via JAK2/STAT3, MAPK/ERK and PI3K/AKT pathways. ConclusionThe present results demonstrated that TMF could stimulate anticancer activity of s180 cancer-bearing mice, induce apoptosis, and inhibit invasion and migration on HepG-2 cells. Our findings displayed a systematic insight into the mechanisms underlying anticancer action of TMF, and provided a better understanding of its use for cancer.