Therapeutic effects of tyroserleutide on lung metastasis of human hepatocellular carcinoma SK-HEP-1 and its mechanism affecting ICAM-1 and MMP-2 and -9

Abstract

BackgroundTyroserleutide (YSL) inhibits the growth and metastasis of human hepatocellular carcinoma (HCC). This paper studied the effect of YSL on metastasis of human HCC and investigated its mechanisms.MethodsIn vivo, experimental lung metastasis models of human HCC SK-HEP-1 cells in nude mice were established, and In vitro, the proliferation, adhesion and invasion of SK-HEP-1 cells were detected.ResultsIn vivo, YSL significantly inhibited the metastasis of human HCC. In vitro, YSL significantly inhibited the proliferation, adhesion and invasion of SK-HEP-1 cells. Through analyses with reverse transcription PCR (RT-PCR) and Western blot, we observed that YSL significantly inhibited the expressions of ICAM-1 in SK-HEP-1 cells. Through RT-PCR, Western blot and zymography methods, YSL was discovered to decrease the mRNA level, protein expression and activity of MMP-2 and -9 in SK-HEP-1 cells.ConclusionWe concluded that YSL could inhibit tumor growth and metastasis of human HCC SK-HEP-1 cells.

Effect and mechanism of action in vitro of cyclodextrin derivative nanoparticles loaded with tyroserleutide on hepatoma

“…These results revealed that free YSL could decrease the basal respiratory rate, mitochondrial oxygen consumption and maximal respiratory rate compared with the control group, suggesting that free YSL could interfere with the correct function of mitochondria. The results are consistent with those reported by Che et al, which indicated that YSL acts directly on mitochondria changing the mitochondrial membrane permeability, reducing mitochondrial membrane potential and accelerating mitochondrial lysis [48]. The results of the mitochondrial respiration test demonstrated that the inhibition of YSL/R6RGD-CMβCD on the mitochondrial respiration of cancer cells was more significant than that of free YSL and YSL/CMβCD.…”

“…The respiratory capacity after the treatment with 0.5 mg ml −1 and 1 mg ml −1 YSL/R6RGD-CMβCD NPs decreased by 35.82% and 53.16%, respectively, compared with that in the negative control group. YSL could also enhance the cell respiration inhibition with the increase of concentration, mainly because YSL could activate the opening of the mitochondrial permeability transition pore in BEL-7402 cells, reduce the mitochondrial membrane potential and increase the concentration of calcium ion in tumor cells [48]. YSL/R6RGD-CMβCD NPs at the concentration of 0.5 mg ml −1 and 1 mg ml −1 resulted in a decrease of the ATP coupling efficiency by 7.39% and 17.43%, respectively, the maximum oxygen consumption decreased by 15.46% and 19.02%, respectively, and the respiratory potential decreased by 23.75% and 28.51%, respectively, compared with the effect exerted by YSL at the same concentration on the same parameters.…”

“…After administration, YSL is mainly distributed in the cytoplasm and mitochondria of tumor cells [4]. Previous studies showed that YSL inhibits the proliferation and tumor formation of the hepatoma cell line BEL-7402, originally established from ascites of patients with hepatic adenocarcinoma, by inducing apoptosis and necrosis of tumor cells in vitro and in vivo [5,6].…”

Inhibition of DDR1 reduces invasive features of human A375 melanoma, HT29 colon carcinoma and SK-HEP hepatoma cells

“…Adhesion of SK-HEP-1 cells to the basal membrane and ECM is mediated by ICAM1 activation [17]. In this work, we established a direct correlation between DDR1 phosphorylation and tumor cell expression of ICAM1 and VCAM1.…”