Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2020; 11:2956-2957.

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

Saroj Nepal, Mi Jin Kim, Jin Tae Hong, Sang Hyun Kim, Dong-Hwan Sohn, Sung Hee Lee, Kyung Song, Dong Young Choi, Eung Seok Lee and Pil-Hoon Park _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:7166-7181. https://doi.org/10.18632/oncotarget.3347

Metrics: PDF 2037 views  |   HTML 2287 views  |   ?  


Abstract

Saroj Nepal1, Mi Jin Kim1, Jin Tae Hong2, Sang Hyun Kim3, Dong-Hwan Sohn4, Sung Hee Lee4, Kyung Song4, Dong Young Choi1, Eung Seok Lee1 and Pil-Hoon Park1

1 College of Pharmacy, Yeungnam University, Gyeongsangbuk-do, Republic of Korea

2 College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea

3 Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

4 Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk, Republic of Korea

Correspondence:

Pil-Hoon Park, email:

Keywords: apoptosis, autophagy, FoxO3A, leptin, p53

Received: October 25, 2014 Accepted: January 15, 2015 Published: January 31, 2015

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 leptin-induced 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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 3347