HMQ‐T‐B10 induces human liver cell apoptosis by competitively targeting EphrinB2 and regulating its pathway

Abstract

Hepatocellular carcinoma (HCC) is a highly prevalent cancer worldwide and it is necessary to discover and develop novel preventive strategies and therapeutic approaches for HCC. Herein, we report that EphrinB2 expression is correlated with liver cancer progression. Moreover, by using phosphorylated proteomics array, we reveal a pro‐apoptosis protein whose phosphorylation and activation levels are up‐regulated upon EphrinB2 knockdown. These results suggest that EphrinB2 may act as an anti‐apoptotic protein in liver cancer cells. We also explored the therapeutic potential of HMQ‐T‐B10 (B10), which was designed and synthesized in our laboratory, for HCC and its underlying mechanisms in vitro and in vivo. Our data demonstrate that B10 could bind EphrinB2 and show inhibitory activity on human liver cancer cells. Moreover, induction of human liver cancer cell apoptosis by B10 could be augmented upon EphrinB2 knockdown. B10 inhibited HCC cell growth and induced HCC cell apoptosis by repressing the EphrinB2 and VEGFR2 signalling pathway. Growth of xenograft tumours derived from Hep3B in nude mice was also significantly inhibited by B10. Collectively, these findings highlight the potential molecular mechanisms of B10 and its potential as an effective antitumour agent for HCC.

Aspernolide A Inhibits the Proliferation of Human Laryngeal Carcinoma Cells through the Mitochondrial Apoptotic and STAT3 Signaling Pathways

“…The OD values were measured at 562 nm with a spectrophotometer (Thermo Fisher Scientific Oy, Vantaa, Finland). Percentage of cell viability ratio = [1 − (OD treatment group − OD blank group )/(OD control group − OD blank group )] × 100% [34]. The inhibition rates and IC 50 values were calculated by GraphPad Prism 6.0 and plotted.…”

Cytotoxic Compounds From Ludwigia hyssopifolia

“…Percentage of cell viability ratio = [ 1 − ( normalO D normalt normalr normale normala normalt normalm normale normaln normalt normalg normalr normalo normalu normalp − normalO D normalb normall normala normaln normalk normalg normalr normalo normalu normalp ) / ( normalO D normalc normalo normaln normalt normalr normalo normall normalg normalr normalo normalu normalp − normalO D normalb normall normala normaln normalk normalg normalr normalo normalu normalp ) ] × 100 normal% . 20 The inhibition rates and IC 50 values were calculated by GraphPad Prism 6.0 and plotted. According to the results, compound 5 and 7 were selected for further analysis with 3 different times (12, 24, and 48 hours).…”

“…Percentage of cell viability ratio = [1(ODtreatment group ODblank group )/(ODcontrol groupODblank group )] × 100% . 20 The inhibition rates and IC 50 values were calculated by GraphPad Prism 6.0 and plotted. According to the results, compound 5 and 7 were selected for further analysis with 3 different times (12,24, and 48 hours).…”

Unraveling the Significance of EPH/Ephrin Signaling in Liver Cancer: Insights into Tumor Progression and Therapeutic Implications

“…EphrinB2: The expression of ephrinB2 is linked to the progression of liver cancer. Dai et al [ 53 ] examined the effects of HMQ-T-B10 (B10) on HCC, both in vitro and in vivo. They showed that B10 was able to inhibit the growth of human liver cancer cells by binding to ephrinB2 and suppressing its signaling pathway, which induced apoptosis.…”