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Thymosin ?10 expression driven by the human TERT promoter induces ovarian cancer-specific apoptosis through ROS production.

ABSTRACT: Thymosin ?(10) (T?(10)) regulates actin dynamics as a cytoplasm G-actin sequestering protein. Previously, we have shown that T?(10) diminishes tumor growth, angiogenesis, and proliferation by disrupting actin and by inhibiting Ras. However, little is known about its mechanism of action and biological function. In the present study, we establish a new gene therapy model using a genetically modified adenovirus, referred to as Ad.TERT.T?(10), that can overexpress the T?(10) gene in cancer cells. This was accomplished by replacing the native T?(10) gene promoter with the human TERT promoter in Ad.TERT.T?(10). We investigated the cancer suppression activity of T?(10) and found that Ad.TERT.T?(10) strikingly induced cancer-specific expression of T?(10) as well as apoptosis in a co-culture model of human primary ovarian cancer cells and normal fibroblasts. Additionally, Ad.TERT.T?(10) decreased mitochondrial membrane potential and increased reactive oxygen species (ROS) production. These effects were amplified by co-treatment with anticancer drugs, such as paclitaxel and cisplatin. These findings indicate that the rise in ROS production due to actin disruption by T?(10) overexpression increases apoptosis of human ovarian cancer cells. Indeed, the cancer-specific overexpression of T?(10) by Ad.TERT.T?(10) could be a valuable anti-cancer therapeutic for the treatment of ovarian cancer without toxicity to normal cells.

SUBMITTER: Kim YC

PROVIDER: S-EPMC3356296 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Thymosin β10 expression driven by the human TERT promoter induces ovarian cancer-specific apoptosis through ROS production.

Kim Young-Chae YC Kim Byoung-Gie BG Lee Je-Ho JH

PloS one 20120518 5

Thymosin β(10) (Tβ(10)) regulates actin dynamics as a cytoplasm G-actin sequestering protein. Previously, we have shown that Tβ(10) diminishes tumor growth, angiogenesis, and proliferation by disrupting actin and by inhibiting Ras. However, little is known about its mechanism of action and biological function. In the present study, we establish a new gene therapy model using a genetically modified adenovirus, referred to as Ad.TERT.Tβ(10), that can overexpress the Tβ(10) gene in cancer cells. Th ...[more]

PMID: 22623951

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Dataset Information

Thymosin ?10 expression driven by the human TERT promoter induces ovarian cancer-specific apoptosis through ROS production.

Publications

Thymosin β10 expression driven by the human TERT promoter induces ovarian cancer-specific apoptosis through ROS production.

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