Targeting calcium signaling in cancer therapy

The intracellular calcium ions (Ca2+) act as second messenger to regulate gene transcription, cell proliferation, migration and death. Accumulating evidences have demonstrated that intracellular Ca2+ homeostasis is altered in cancer cells and the alteration is involved in tumor initiation, angiogenesis, progression and metastasis. Targeting derailed Ca2+ signaling for cancer therapy has become an emerging research area. This review summarizes some important Ca2+ channels, transporters and Ca2+-ATPases, which have been reported to be altered in human cancer patients. It discusses the current research effort toward evaluation of the blockers, inhibitors or regulators for Ca2+ channels/transporters or Ca2+-ATPase pumps as anti-cancer drugs. This review is also aimed to stimulate interest in, and support for research into the understanding of cellular mechanisms underlying the regulation of Ca2+ signaling in different cancer cells, and to search for novel therapies to cure these malignancies by targeting Ca2+ channels or transporters

Autophagy of umbilical cord mesenchymal stem cells induced by rapamycin conduces to pro-angiogenic function of the conditioned medium

Angiogenesis is critical for wound healing and tissue repair. Umbilical cord mesenchymal stem cells (UCMSCs)-conditioned medium has certain actions to promote angiogenesis, and is expected for wound healing and tissue repair. However, recent studies showed that the pro-angiogenic efficacy of unprocessed MSCs-conditioned medium is low, and insufficient for tissue repair. Autophagy is a process for protein recycling and a contributor for cell exocrine, which may enhance pro-angiogenic efficacy of the conditioned medium by stimulating cytokine release from UCMSCs. Therefore, in this study we attempted to obtain enhanced autophagy in UCMSCs using different concentrations of rapamycin and compared pro-angiogenic functions of the conditioned media. The in vitro data showed that although 100 nM-10 μM rapamycin all could induce autophagy in UCMSCs, 100 nM was the best dose to optimize the angiogenic effect of the conditioned medium. The in vivo data also showed that pro-angiogenic effect of the optimized conditioned medium was more obvious than that of the control conditioned medium (0 nM group) in the injected matrigel plaques. Further, the expressions of VEGF, FGF-2, MMP-9, PDGF-α and PDGF-β were markedly increased in UCMSCs treated with 100 nM rapamycin. In conclusion, appropriately enhancing autophagy of UCMSC can improve pro-angiogenic efficacy of the conditioned medium, which may optimize therapeutic applications of UCMSCs-conditioned medium in wound healing and tissue repair