APO-1

Cardiosphere-derived cells (CDCs) are progenitor cells derived from heart tissue and have shown promising results in preclinical models. APOSEC, the secretome of irradiated peripheral blood mononuclear cells, has decreased infarct size in acute and chronic experimental myocardial infarction (MI). We enhanced the effect of CDCs with APOSEC preconditioning (apoCDC) and investigated the reparative effect in a translational pig model of reperfused MI. Supernatants of CDCs, assessed by proteomic analysis, revealed reduced production of extracellular matrix proteins after in vitro APOSEC preconditioning. In a porcine model of catheter-based reperfused anterior acute MI (AMI), CDCs with (apoCDC, n = 8) or without APOSEC preconditioning (CDC, n = 6) were infused intracoronary, 15 min after the start of reperfusion. Untreated AMI animals (n = 7) and sham procedures (n = 5) functioned as controls. 2-deoxy-2-(18 F)-fluoro-D-glucose-positron emission tomography-magnetic resonance imaging ([¹⁸F]FDG-PET-MRI), with late enhancement after 1 month, showed reduced scar volume and lower transmurality of the infarcted area in CDC and apoCDC compared to AMI controls. Segmental quantitative PET images displayed indicated more residual viability in apoCDC. The left-ventricle (LV) ejection fraction was improved nonsignificantly to 45.8% ± 8.6% for apoCDC and 43.5% ± 7.1% for CDCs compared to 38.5% ± 4.4% for untreated AMI. Quantitative hybrid [¹⁸F]FDG-PET-MRI demonstrated improved metabolic and functional recovery after CDC administration, whereas apoCDCs induced preservation of viability of the infarcted area.

Betulinic acid (BA), isolated from the tree bark, is a pentacyclic triterpenoid, showing inhibitory role in cancer cells. However, the effects of BA treatment on liver cancer have little to be known. Thus, the study is conducted to explore the in vitro and in vivo role of BA in liver cancer. And the interactions between BA and tumor necrosis factor-related apoptosis-inducing ligand of APO2, also known as TRAIL, were investigated in liver cancer cells. A synergistic effect of BA and APO2 combination on apoptosis induction in liver cancer cells was observed. The cancer cells were insensitive to APO2 single therapy. However, liver cancer cells receiving BA were sensitive to APO2-triggered apoptotic response by enhancing Caspases cleavage, due to elevation of decoy receptor 1 and 2 (DcR1 and DcR2) dependent on p53. Bcl-2 family members of Bcl-2 and Mcl-1, belonging to anti-apoptosis, were decreased, whereas Bad and Bak, as pro-apoptotic members, were increased for BA and APO2 combined treatment. Additionally, the mouse xenograft model suggested that BA and APO2 in combination markedly inhibited liver cancer growth in comparison to BA or APO2 monotherapy without toxicity. The present study revealed a dramatically therapeutic strategy for promoting APO2-induced anti-cancer effects on liver cancer cells via BA combination.