PMID- 25356800
OWN - NLM
STAT- MEDLINE
DCOM- 20150805
LR  - 20211203
IS  - 1532-7914 (Electronic)
IS  - 0163-5581 (Linking)
VI  - 66
IP  - 8
DP  - 2014
TI  - Bovine lactoferrin induces cell cycle arrest and inhibits mTOR signaling in 
      breast cancer cells.
PG  - 1371-85
LID - 10.1080/01635581.2014.956260 [doi]
AB  - Lactoferrin (LF) is predominantly found in mammalian secretions with recognized 
      anticancer potential, although the mechanisms involved in such activity are still 
      unclear. Here, the stability, internalization, and cytotoxicity of bovine LF 
      (bLF) and its variants were tested against a panel of breast cancer cells. bLF 
      was found to be very stable under incubation with cells and also able to 
      internalize them, although most of the protein remained in the culture medium. 
      Furthermore, bLF (up to 30 muM) inhibited the growth of breast cancer cells 
      (T-47D, MDA-MB-231, Hs578T, and MCF-7) in a higher extent than in the normal 
      counterpart cell line (MCF-10-2A), thus suggesting its selectivity. Regarding its 
      variants, only the iron-saturated protein showed a higher activity compared with 
      the commercial bLF. bLF growth inhibitory activity was associated with the 
      induction of cell cycle arrest, but not with apoptosis. Moreover, exposure to bLF 
      increased the cells phospho-AMPKalpha levels and decreased both phospho threonine 
      mammalian target of rapamycin (mTOR) and total mTOR levels, indicating a novel 
      mechanism of action through its ability to induce nutrient/energy-related stress. 
      This study disclosed important findings to better understand the mechanisms 
      underlying the bLF effects on breast cancer cell lines, which could be valuable 
      for novel advances in the cancer research field.
FAU - Zhang, Yunlei
AU  - Zhang Y
AD  - a Centre of Biological Engineering, University of Minho, Braga Portugal and 
      College of Life Science, Hunan Provincial Key Laboratory of Microbial Molecular 
      Biology-State Key Laboratory Breeding Base of Microbial Molecular Biology , Hunan 
      Normal University , Changsha , China.
FAU - Nicolau, Ana
AU  - Nicolau A
FAU - Lima, Cristovao F
AU  - Lima CF
FAU - Rodrigues, Ligia R
AU  - Rodrigues LR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141030
PL  - United States
TA  - Nutr Cancer
JT  - Nutrition and cancer
JID - 7905040
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.4.21.- (Lactoferrin)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/metabolism
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Breast Neoplasms/*metabolism
MH  - Cattle
MH  - Cell Cycle Checkpoints/*drug effects
MH  - Cell Line, Tumor
MH  - Down-Regulation
MH  - Female
MH  - Humans
MH  - Lactoferrin/*pharmacology
MH  - MCF-7 Cells
MH  - Phosphorylation
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
EDAT- 2014/10/31 06:00
MHDA- 2015/08/06 06:00
CRDT- 2014/10/31 06:00
PHST- 2014/10/31 06:00 [entrez]
PHST- 2014/10/31 06:00 [pubmed]
PHST- 2015/08/06 06:00 [medline]
AID - 10.1080/01635581.2014.956260 [doi]
PST - ppublish
SO  - Nutr Cancer. 2014;66(8):1371-85. doi: 10.1080/01635581.2014.956260. Epub 2014 Oct 
      30.