Autophagy induction by leptin contributes to suppression of apoptosis in cancer cells and xenograft model: Involvement of p53/FoxO3A axis

Title
Autophagy induction by leptin contributes to suppression of apoptosis in cancer cells and xenograft model: Involvement of p53/FoxO3A axis
Author(s)
박필훈네팔사로지김미진홍진태[홍진태]김상현[김상현]손동환[손동환]이성희[이성희]송경[송경]최동영이응석
Keywords
FOXO TRANSCRIPTION FACTORS; ETHANOL-INDUCED APOPTOSIS; ACTIVATED PROTEIN-KINASE; BREAST-CANCER; TUMOR-CELL; MATRIX METALLOPROTEINASES; MOLECULAR-MECHANISMS; INHIBITS APOPTOSIS; FORKHEAD FOXO3A; GROWTH-FACTOR
Issue Date
201503
Publisher
IMPACT JOURNALS LLC
Citation
ONCOTARGET, v.6, no.9, pp.7166 - 7181
Abstract
Leptin, a hormone mainly produced from adipose tissue, has been shown to induce proliferation of cancer cells. However, the molecular mechanisms underlying leptin-induced tumor progression have not been clearly elucidated. In the present study, we investigated the role of autophagy in leptin-induced cancer cell proliferation using human hepatoma (HepG2) and breast cancer cells (MCF-7), and tumor growth in a xenograft model. Herein, we showed that leptin treatment caused autophagy induction as assessed by increase in expression of autophagy-related genes, including beclin-1, Atg5 and LC3 II, further induction of autophagosome formation and autophagic flux. Interestingly, inhibition of autophagic process by treatment with inhibitors and LC3B gene silencing blocked leptin-induced increase in cell number and suppression of apoptosis, indicating a crucial role of autophagy in leptin-induced tumor progression. Moreover, gene silencing of p53 or FoxO3A prevented leptininduced LC3 II protein expression, suggesting an involvement of p53/FoxO3A axis in leptin-induced autophagy activation. Leptin administration also accelerated tumor growth in BALB/c nude mice, which was found to be autophagy dependent. Taken together, our results demonstrate that leptin-induced tumor growth is mediated by autophagy induction and autophagic process would be a promising target to regulate development of cancer caused by leptin production.
URI
http://hdl.handle.net/YU.REPOSITORY/33159
ISSN
1949-2553
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약학대학 > 약학부 > Articles
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