Hydroxysafflor yellow�A induces autophagy in human liver cancer cells by regulating Beclin�1 and ERK expression

Abstract

Hydroxysafflor yellow A (HSYA) is a water-soluble component of the safflower (Carthamus tinctorius), and research has revealed that HSYA exhibits antitumor effects. In the present study, the effects of HSYA on the autophagy of a Hep-G2 liver cancer cell line, as well as the underlying mechanisms, were investigated. Hep-G2 cells were treated with HSYA and the viability of cells was measured using an MTT assay. Western blotting and immunofluorescence assays were performed to determine the expression of light chain 3 II (LC3-II) and p62, as well as the autophagy regulators Beclin 1 and ERK1/2. Transmission electron microscopy was performed to observe the formation of autophagosomes. The combined effects of HSYA and the autophagy inhibitor chloroquine (CQ) were also determined. The results revealed that the viability of Hep-G2 cells decreased with increasing concentrations of HSYA. Furthermore, LC3-II expression increased significantly and the level of p62 decreased significantly in the HYSA group compared with the control group. Additionally, an increase in Beclin 1 expression and a decrease in phosphorylated-ERK1/2 expression was observed in Hep-G2 cells treated with HYSA. Following treatment with CQ and HSYA, a significant increase in the viability of Hep-G2 cells was observed compared with the HSYA group. Collectively, the results indicated that HSYA induced autophagy by promoting the expression of Beclin 1 and inhibiting the phosphorylation of ERK in liver cancer cells. Therefore, HSYA may serve as a potential therapeutic agent for liver cancer.

Autophagy: Mechanisms and Therapeutic Potential of Flavonoids in Cancer

“…Lin et al firstly found that isoliquiritigenin combined with a specific concentration of doxorubicin has a synergistic cytotoxic effect on multidrug-resistant human uterine sarcoma cell line MES-SA/Dx5, but it is more effective on MES-SA/Dx5-R cells with a high drug resistance. ISL regulated the expression of Bcl-2, the mTOR pathway, and the expression of other related proteins, triggering apoptosis and autophagy in drug-resistant tumor cells, while the inhibition of autophagy enhanced ISL-mediated drug-resistant cell death [ 88 ]. Some studies have shown that the resistance of human glioblastoma cells (GBM8901) to temozolomide (TMZ) is associated with the expression of O6-methylguanine-DNA-methyltransferase (MGMT), while TMZ-induced autophagy depends on the expression of MGMT [ 60 ].…”

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

“…In addition, chalcones capable of inducing autophagy include hydroxysafflor yellow A [ 143 ], cardamonin [ 105 ], panduratin A [ 163 ], bavachalcone (isolated from Cullen corylifolium) [ 111 ], trans-chalcone [ 164 ], or α,2′-dihydroxy-4,4′-dimethoxydihydrochalcone, isolated from Cedrela odorata (Meliaceae) [ 165 ].…”

Bioactive Substances in Safflower Flowers and Their Applicability in Medicine and Health-Promoting Foods

“…HSYA inhibits the development of cancers [45,51,[89][90][91][92][93]. It inhibited angiogenesis of liver cancer by blocking the ERK/MAPK [89,94] and NF/ K B HSYA signaling pathway in mice [89] and via inhibiting p38MAPK phosphorylation [91]. Administration of HSYA enhanced spleen and thymus indicators and immune system function [67] (i) Increase in the synthesis of antioxidant enzymes in adipose tissue and in the liver (i) Increase of expression of antioxidant enzymes and Nrf2 in adipocytes, liver tissue, and HepG2 cells (ii) Regulation of glucose metabolism and liver function [50] 16…”

“…HSYA inhibits the development of cancers [ 45 , 51 , 89 – 93 ]. It inhibited angiogenesis of liver cancer by blocking the ERK/MAPK [ 89 , 94 ] and NF/ K B HSYA signaling pathway in mice [ 89 ] and via inhibiting p38MAPK phosphorylation [ 91 ]. Administration of HSYA enhanced spleen and thymus indicators and immune system function [ 89 ] and resulted in reduced viability, proliferation, and migration of HepG2 tumor cells [ 91 ].…”