Lidamycin decreases CD133 expression in hepatocellular carcinoma via the Notch signaling pathway

Abstract

Abstract. Cluster of differentiation (CD)133 is considered a molecular marker of cancer stem cells in hepatocellular carcinoma. In the present study, the effect of lidamycin (LDM) on CD133 expression in hepatocellular carcinoma (Huh7 cells) was evaluated and the potential molecular mechanism was investigated. Flow cytometry analysis, as well as sorting, sphere formation and western-blot assays, were performed in vitro to explore the effects of LDM on CD133 expression. A subcutaneous tumor model in nude mice was used to observe the effects of LDM on tumor volume and CD133 protein in vivo. To investigate the potential underlying molecular mechanism, Notch signaling pathway activity was detected by western blot analysis and reverse transcription-quantitative polymerase chain reaction. The proportion of CD133 + cells and the expression of CD133 protein were revealed to be downregulated by LDM. Sphere formation of sorted CD133 + cells was suppressed 7 days after LDM treatment. In addition, LDM inhibited tumor volume formed from sorted CD133 + cells and CD133 protein level in vivo. LDM decreased the mRNA level of NOTCH1, Hes1 (Hes family BHLH transcription factor 1) and Hey1 (Hes-related family BHLH transcription factor with YRPW motif 1) genes; consequently, the protein expression of NOTCH1, Notch intracellular domain, Hes1 and Hey1 was decreased by LDM. Downregulation of the Notch signaling pathway by LDM was enhanced through combination with N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester. In brief, these data suggest that LDM suppresses CD133 expression via the Notch signaling pathway, indicating the potential mechanism of LDM on CD133 and the benefits for further clinical application.

Anti-endometriosis Mechanism of Jiawei Foshou San Based on Network Pharmacology

“…The protein were separated and extracted from eutopic endometrium in control group and ectopic endometrium in other groups. The tissue lysates were prepared as described previously ( Chen et al, 2015 , 2017 ). Briefly quantified protein lysates were separated by SDS-PAGE, transferred to polyvinylidene difluoride membrane (Millipore, United States) and probed with primary rabbit anti-MMP-2, rabbit anti-MMP-9 (1:100 dilution; Boster Biological Technology, Wuhan, China), rabbit anti-TIMP-1 (1:300 dilution; Proteintech Biotechnology, Wuhan, China), rabbit anti-E-cadherin, rabbit anti-Vimentin, rabbit anti-Snail, rabbit anti-Slug (1:1000 dilution; Cell Signaling Technology, Beverly, MA, United States), rabbit anti-β-actin (1:5000 dilution; Proteintech Biotechnology, Wuhan, China) overnight at 4°C.…”

The Intricate Notch Signaling Dynamics in Therapeutic Realms of Cancer

“…In hepatocellular carcinomas, Lidamycin inhibits the Notch pathway, thereby decreasing the expression of CD133, along with the mRNA of HES1, HEY1, and Notch1 genes. 139 Resveratrol (RES), a naturally occurring phytoalexin, produced by plants in response to stress, injury, and fungal infection, has chemopreventive properties. It inhibits the survival signaling pathways such as Notch and PI3k/Akt and their downstream genes.…”

“…Lidamycin (LDM) is an antibiotic having a discrete antitumor effect in various types of malignancies such as liver, breast, lungs, and colon. In hepatocellular carcinomas, Lidamycin inhibits the Notch pathway, thereby decreasing the expression of CD133, along with the mRNA of HES1, HEY1, and Notch1 genes …”

The Carcinogenic Role of the Notch Signaling Pathway in the Development of Hepatocellular Carcinoma

“…Additionally, the protein levels of Notch1, Notch intracellular domain, Hey1, and Hes1 were also decreased in LDM-treated in Huh7 cells. However, further clinical evaluation of LDM is required 99.…”