While reinforcing cell cycle arrest, rapamycin and Torins suppress senescence in UVA-irradiated fibroblasts

Olga V. Leontieva; Mikhail V. Blagosklonny

doi:10.18632/oncotarget.17827

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Research Papers:

While reinforcing cell cycle arrest, rapamycin and Torins suppress senescence in UVA-irradiated fibroblasts

Olga V. Leontieva and Mikhail V. Blagosklonny _

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Oncotarget. 2017; 8:109848-109856. https://doi.org/10.18632/oncotarget.17827

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Abstract

Olga V. Leontieva1 and Mikhail V. Blagosklonny1

1 Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA

Correspondence to:

Mikhail V. Blagosklonny, email:

Olga V. Leontieva, email:

Keywords: mTORC1, rapalogs, sirolimus, aging, cancer, UVA

Received: January 20, 2017 Accepted: May 02, 2017 Published: May 11, 2017

Abstract

Sunlight predisposes to skin cancer and melanomas. Ultraviolet A (UVA), a long wave component of sunlight, can reach dermal fibroblasts. Here we studied UVA-induced senescence in human fibroblasts in vitro. It is known that senescence occurs, when cell cycle is arrested, but mTOR is still active, thus converting arrest to senescence (geroconversion). We showed that, while arresting cell cycle, UVA did not inhibit mTOR, enabling geroconversion. In UVA-treated cells, mTOR remained fully active. Rapamycin and Torins 1/ 2 prevented UVA-induced senescent phenotype, although they further re-enforced cell cycle arrest. Given that senescent stromal fibroblasts support tumorigenesis, we envision that mTOR inhibitors may potentially be used to prevent sunlight-caused tumors as well as skin photo-aging.

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Research Papers:

While reinforcing cell cycle arrest, rapamycin and Torins suppress senescence in UVA-irradiated fibroblasts

Abstract