Thumbnail
Access Restriction
Open

Author Yu, Min ♦ Li, Ruishu ♦ Zhang, Juan
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ANTIBIOTICS ♦ APOPTOSIS ♦ ATP ♦ CARNITINE ♦ CELL PROLIFERATION ♦ DEACTIVATION ♦ IN VITRO ♦ IN VIVO ♦ INHIBITION ♦ MAMMARY GLANDS ♦ MEMBRANES ♦ MICE ♦ MITOCHONDRIA ♦ NEOPLASMS ♦ RESPIRATION ♦ SENSITIVITY ♦ URACILS
Abstract Targeting mitochondrial biogenesis has become a potential therapeutic strategy in cancer due to their unique metabolic dependencies. In this study, we show that levofloxacin, a FDA-approved antibiotic, is an attractive candidate for breast cancer treatment. This is achieved by the inhibition of proliferation and induction of apoptosis in a panel of breast cancer cell lines while sparing normal breast cells. It also acts synergistically with conventional chemo drug in two independent in vivo breast xenograft mouse models. Importantly, levofloxacin inhibits mitochondrial biogenesis as shown by the decreased level of mitochondrial respiration, membrane potential and ATP. In addition, the anti-proliferative and pro-apoptotic effects of levofloxacin are reversed by acetyl-L-Carnitine (ALCAR, a mitochondrial fuel), confirming that levofloxacin's action in breast cancer cells is through inhibition of mitochondrial biogenesis. A consequence of mitochondrial biogenesis inhibition by levofloxacin in breast cancer cells is the deactivation of PI3K/Akt/mTOR and MAPK/ERK pathways. We further demonstrate that breast cancer cells have increased mitochondrial biogenesis than normal breast cells, and this explains their different sensitivity to levofloxacin. Our work suggest that levofloxacin is a useful addition to breast cancer treatment. Our work also establish the essential role of mitochondrial biogenesis on the activation of PI3K/Akt/mTOR and MAPK/ERK pathways in breast cancer cells. - Highlights: • Levofloxacin targets a panel of breast cancer cell lines in vitro and in vivo. • Levofloxacin acts synergistically with 5-Fluorouracil in breast cancer. • Levofloxacin targets breast cancer cells via inhibiting mitochondrial biogenesis. • Breast cancer cells have increased mitochondrial biogenesis than normal cells. • Mitochondrial biogenesis inhibition lead to deactivation of PI3K/Akt/mTOR pathway.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-03-18
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 471
Issue Number 4


Open content in new tab

   Open content in new tab