PMID- 27062892
OWN - NLM
STAT- MEDLINE
DCOM- 20170126
LR  - 20170126
IS  - 1872-7786 (Electronic)
IS  - 0009-2797 (Linking)
VI  - 252
DP  - 2016 May 25
TI  - Targeting HSP90/Survivin using a cell permeable structure based peptido-mimetic 
      shepherdin in retinoblastoma.
PG  - 141-9
LID - S0009-2797(16)30134-X [pii]
LID - 10.1016/j.cbi.2016.04.011 [doi]
AB  - BACKGROUND: Retinoblastoma (RB) is a childhood retinal malignancy. Effective 
      therapeutic strategies are still being investigated in RB disease management. 
      Here, the anti-cancer effect of shepherdin, a peptido-mimetic inhibiting heat 
      shock protein (HSP90)-Survivin interaction has been analyzed. METHODS: We 
      analyzed HSP (HSP70/90) and Survivin protein expressions by immunohistochemistry 
      (29 archival tumors), qRT-PCR, FACS and Western analysis (10 un-fixed RB tumors). 
      We also analyzed cellular cytotoxicity and anti-proliferative effect in peptide 
      treated RB cells (Y79, Weri Rb1) and MIO-M1 cells. RESULTS: Heterogeneous 
      expressions of HSP70/90 and Survivin with a significant association between HSP70 
      and HSP90 (r(2) = 0.59, p = 0.001) was observed. In RB cells, anti-tumor effects 
      were detected with 0.42 mug/ml of shepherdin at 4 h s of serum starvation. 
      Decreased Survivin, Bcl2, MMP-2 activity with increased Bax, Bim, and Caspase-9 
      protein expressions were noticed. No significant changes were observed in 
      shepherdin treated non-neoplastic MIO-M1, nor in scramble-peptide treated RB 
      cells. CONCLUSION: The presence of HSPs (HSP70/90) and Survivin reveals multiple 
      cellular mechanisms adopted by RB cells during cancer progression. Serum 
      starvation induced HSP90 whose interactions with Survivin were specifically 
      inhibited by shepherdin. The associated molecular shuffling has been reported. 
      These findings strongly implicate the potential of targeting HSP90-Survivin 
      interaction as an adjuvant therapy in RB management.
CI  - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
FAU - Venkatesan, Nalini
AU  - Venkatesan N
AD  - Department of Larsen & Toubro Ocular Pathology, Vision Research Foundation, 
      Sankara Nethralaya, 18/41, College Road, Chennai 600006, India; Birla Institute 
      of Technology and Science (BITS), Pilani, Rajasthan 333031, India.
FAU - Kanwar, Jagat R
AU  - Kanwar JR
AD  - Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), 
      School of Medicine (SoM), Molecular and Medical Research (MMR) Strategic Research 
      Centre, Faculty of Health, Deakin University, Pigdons Road, Waurn Ponds, Geelong, 
      Victoria 3217, Australia.
FAU - Deepa, Perinkulam Ravi
AU  - Deepa PR
AD  - Department of Biological Sciences, Birla Institute of Technology and Science 
      (BITS), Pilani, Rajasthan 333031, India.
FAU - Navaneethakrishnan, Saranya
AU  - Navaneethakrishnan S
AD  - Department of Larsen & Toubro Ocular Pathology, Vision Research Foundation, 
      Sankara Nethralaya, 18/41, College Road, Chennai 600006, India.
FAU - Joseph, Chitra
AU  - Joseph C
AD  - Department of Larsen & Toubro Ocular Pathology, Vision Research Foundation, 
      Sankara Nethralaya, 18/41, College Road, Chennai 600006, India.
FAU - Krishnakumar, Subramanian
AU  - Krishnakumar S
AD  - Department of Larsen & Toubro Ocular Pathology, Vision Research Foundation, 
      Sankara Nethralaya, 18/41, College Road, Chennai 600006, India. Electronic 
      address: drkrishnakumar_2000@yahoo.com.
LA  - eng
PT  - Journal Article
DEP - 20160407
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Antineoplastic Agents)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (HSP90 Heat-Shock Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (shepherdin)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - HSP70 Heat-Shock Proteins/metabolism
MH  - HSP90 Heat-Shock Proteins/*metabolism
MH  - Humans
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Peptide Fragments/*pharmacology
MH  - Retina/*drug effects/metabolism/pathology
MH  - Retinal Neoplasms/*drug therapy/metabolism/pathology
MH  - Retinoblastoma/*drug therapy/metabolism/pathology
OTO - NOTNLM
OT  - Heat shock proteins
OT  - Peptido-mimetic (shepherdin)
OT  - Retinoblastoma
OT  - Survivin
EDAT- 2016/04/12 06:00
MHDA- 2017/01/27 06:00
CRDT- 2016/04/12 06:00
PHST- 2015/10/03 00:00 [received]
PHST- 2016/03/07 00:00 [revised]
PHST- 2016/04/05 00:00 [accepted]
PHST- 2016/04/12 06:00 [entrez]
PHST- 2016/04/12 06:00 [pubmed]
PHST- 2017/01/27 06:00 [medline]
AID - S0009-2797(16)30134-X [pii]
AID - 10.1016/j.cbi.2016.04.011 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2016 May 25;252:141-9. doi: 10.1016/j.cbi.2016.04.011. Epub 
      2016 Apr 7.