Cytotoxic 4-Hydroxyprorocentrolide and Prorocentrolide C from Cultured DinoflagellateProrocentrum limaInduce Human Cancer Cell Death through Apoptosis and Cell Cycle Arrest
TOXINS
Authors: Lee, Seon Min; Kim, Na-Hyun; Jeong, Eun Ju; Rho, Jung-Rae
Abstract
Prorocentrolide and its analogs, the novel naturally derived antitumor agents, have recently been identified in the dinoflagellateProrocentrum lima. In the current study, the underlying inhibitory mechanisms of 4-hydroxyprorocentrolide (1) and prorocentrolide C (2) on the proliferation of human carcinoma cells were determined.1and2arrested the cell cycle at the S phase in A549 cells and G2/M phase in HT-29 cells, leading to apoptotic cell death, as determined using fluorescence-activated cell sorting analysis with Annexin V/PI double staining. Apoptosis induced by these compounds was associated with alterations in the expression of cell cycle-regulating proteins (cyclin D1, cyclin E1, CDK2, and CDK4), as well as alterations in the levels of apoptosis-related proteins (PPAR, Bcl-2, Bcl-xl, and survivin). These findings provide new insights into the antitumor mechanisms of 4-hydroxyprorocentrolide and prorocentrolide C and a basis for future investigations assessing prorocentrolide analogs as prospective therapeutic drugs.
Comparison of exosomes derived from induced pluripotent stem cells and mesenchymal stem cells as therapeutic nanoparticles for treatment of corneal epithelial defects
AGING-US
Authors: Wang, Shudan; Hou, Yunlong; Li, Xuran; Song, Zhen; Sun, Baoqi; Li, Xinyue; Zhang, Hong
Abstract
Induced pluripotent stem cells and mesenchymal stem cells are pluripotent stem cells that represent promising therapies for treating various tissue injuries and wound healing. Exosomes are nanosized extracellular vesicles that have been identified as important mediators of therapeutic functions, which are performed via cell communication. In this study, we compared the efficacy of induced pluripotent stem cells-derived exosomes (iPSCs-Exos) and mesenchymal stem cells-derived exosomes (MSCs-Exos) in treating corneal epithelial defects. The characteristics of the two types of exosomes were not significantly different. Compared to MSCs-Exos, iPSCs-Exos had a better in vitro effect on the proliferation, migration, cell cycle promotion and apoptosis inhibition of human corneal epithelial cells. iPSCs/MSCs-Exos promoted cell regeneration by upregulating cyclin A and CDK2 to drive HCECs to enter the S phase from the G0/G1 phase. In vivo results from a corneal epithelial defect model showed that both iPSCs-Exos and MSCs-Exos accelerated corneal epithelium defect healing while the effects of iPSCs-Exos were much stronger than those of MSCs-Exos. This study demonstrated that iPSCsExos had a better therapeutic effect on corneal epithelial defect healing. Thus, a novel potential nanotherapeutic strategy for treating corneal epithelial defects and even more ocular surface disease could be undertaken by using iPSCs-Exos dissolved in eye drops.