title: NOV-002, A Glutathione Disulfide Mimetic, Suppresses Tumor Cell Invasion and Metastasis.
abstract: Metastasis is the major cause of death in cancer. Most therapies currently in the clinic aim to eradicate primary tumor, but do not have ideal effects on metastasis. The lack of effective therapy in metastasis prevention and treatment results in high mortality rate in cancer patients with advanced diseases. Here we report the oxidized glutathione small molecule compound NOV-002 reduces cancer cell invasionin vitroand metastasis in an animal model in combination with chemotherapy drug gemcitabine. NOV-002 regulates cell signaling pathways by suppressing ErbB2 and PI3K phosphorylation and subsequent inhibition of Akt and RhoA activation. Our results suggest that NOV-002 affects cell signaling pathways that are critical for invasion and metastasis and can potentially be effective in metastasis treatment in combination of other chemotherapies.
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Kiranmai
authors.initials: K
authors.lastname: Gumireddy
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Anping
authors.initials: A
authors.lastname: Li
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA ; Central labortary, Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014, P. R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Cao
authors.affiliation: University of Washington Medical Center, 1959 N.E. Pacific Street, Seattle, WA 98195, USA.
authors.forename: Jinchun
authors.initials: J
authors.lastname: Yan
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA ; Department of Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xu
authors.affiliation: Novelos Therapeutics Inc. One Gateway Center, Newton, MA 02458, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Pazoles
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Qihong
authors.initials: Q
authors.lastname: Huang