PMID- 30393482
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220330
IS  - 1734-1922 (Print)
IS  - 1896-9151 (Electronic)
IS  - 1734-1922 (Linking)
VI  - 14
IP  - 6
DP  - 2018 Oct
TI  - Inositol-6 phosphate inhibits the mTOR pathway and induces autophagy-mediated 
      death in HT-29 colon cancer cells.
PG  - 1281-1288
LID - 10.5114/aoms.2018.76935 [doi]
AB  - INTRODUCTION: Colorectal cancer (CRC) is common, with a worldwide incidence 
      estimated at more than 1 million cases annually. Therefore, the search for agents 
      for CRC treatment is highly warranted. Inositol-6 phosphate (IP(6)) is enriched 
      in rice bran and possesses many beneficial effects. In the present study the 
      effect of IP6 on autophagy-mediated death by modulating the mTOR pathway in HT-29 
      colon cancer cells was studied. MATERIAL AND METHODS: Autophagy was assessed by 
      acridine orange (AO) staining, transmission electron microscopy, and western 
      blotting to detect LC3-II and Beclin 1. Akt/mTOR signaling protein expression was 
      also analyzed by western blotting. Apoptosis was analyzed by annexin V staining. 
      RESULTS: Incubation of cells with IP(6) resulted in downregulation of the p-Akt 
      at 3h. Along with that confocal microscopic analysis of p-AKT, IP(6) 
      administration resulted that a diminished expression of p-Akt. mTOR pathway 
      regulates autophagy and incubation with IP6 to HT-29 cells showed decreased 
      expression of p-70S6Kinase, 4-EBP-1 in a time-dependent manner. Inositol-6 
      phosphate (10 mug/ml, 24 and 48 h) induced autophagic vesicles, as confirmed by AO 
      staining and transmission electron microscopy. We also found increased expression 
      of LC3-II and Beclin 1 in a time-dependent manner after incubation with IP(6). 
      Furthermore, IP(6) induced apoptosis, as revealed by annexin V staining. 
      CONCLUSIONS: Our results clearly indicate that IP6 induces autophagy by 
      inhibiting the Akt/mTOR pathway.
FAU - Pandurangan, Ashok Kumar
AU  - Pandurangan AK
AD  - Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala 
      Lumpur, Malaysia.
AD  - Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, 
      Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
FAU - Ismail, Salmiah
AU  - Ismail S
AD  - Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, 
      Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
FAU - Esa, Norhaizan Mohd
AU  - Esa NM
AD  - Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, 
      Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
FAU - Munusamy, Murugan A
AU  - Munusamy MA
AD  - Department of Botany and Microbiology, College of Science, King Saud University, 
      Riyadh, Saudi Arabia.
LA  - eng
PT  - Journal Article
DEP - 20180705
PL  - Poland
TA  - Arch Med Sci
JT  - Archives of medical science : AMS
JID - 101258257
PMC - PMC6209706
OTO - NOTNLM
OT  - apoptosis
OT  - autophagy
OT  - colorectal cancer
OT  - inositol-6-phosphate
OT  - mammalian target of rapamycin
COIS- The authors declare no conflict of interest.
EDAT- 2018/11/06 06:00
MHDA- 2018/11/06 06:01
PMCR- 2018/10/01
CRDT- 2018/11/06 06:00
PHST- 2017/01/06 00:00 [received]
PHST- 2017/01/12 00:00 [accepted]
PHST- 2018/11/06 06:00 [entrez]
PHST- 2018/11/06 06:00 [pubmed]
PHST- 2018/11/06 06:01 [medline]
PHST- 2018/10/01 00:00 [pmc-release]
AID - 33250 [pii]
AID - 10.5114/aoms.2018.76935 [doi]
PST - ppublish
SO  - Arch Med Sci. 2018 Oct;14(6):1281-1288. doi: 10.5114/aoms.2018.76935. Epub 2018 
      Jul 5.