title: Cytotoxicity and Selectivity in Skin Cancer by SapC-DOPS Nanovesicles.
abstract: Squamous cell carcinoma (SCC) and melanoma are malignant human cancers of the skin with an annual mortality that exceed 10,000 cases every year in the USA alone. In this study, the lysosomal protein saposin C (SapC) and the phospholipid dioloylphosphatidylserine (DOPS) were assembled into cancer-selective nanovesicles (SapC-DOPS) and successfully tested using severalin vitroandin vivoskin cancer models. Using MTT assay that measures the percentage of cell death, SapC-DOPS cytotoxic effect on three skin tumor cell lines (squamous cell carcinoma, SK-MEL-28, and MeWo) was compared to two normal nontumorigenic skin cells lines, normal immortalized keratinocyte (NIK) and human fibroblast cell (HFC). We observed that the nanovesicles selectively killed the skin cancer cells by inducing apoptotic cell death whereas untransformed skin cancer cells remained unaffected. Using subcutaneous skin tumor xenografts, animals treated with SapC-DOPS by subcutaneous injection showed a 79.4 % tumor reduced compared to the control after 4 days of treatment. We observed that the nanovesicles killed skin cancer cells by inducing apoptotic cell death compared to the control as revealed by TUNEL staining of xenograft tumor sections.
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH.
authors.forename: Shadi
authors.initials: S
authors.lastname: Abu-Baker
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH ; Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Chu
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH ; Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Stevens
authors.affiliation: Department of Dermatology, University of Miami, Miami, FL.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH ; Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Qi