Targeting HSP90/survivin using a cell permeable structure based peptido-mimetic shepherdin in retinoblastoma

Venkatesan, Nalini, Kanwar, Jagat R., Deepa, Perinkulam Ravi, Navaneethakrishnan, Saranya, Joseph, Chitra and Krishnakumar, Subramanian 2016, Targeting HSP90/survivin using a cell permeable structure based peptido-mimetic shepherdin in retinoblastoma, Chemico-biological interactions, vol. 252, pp. 141-149, doi: 10.1016/j.cbi.2016.04.011.

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Title Targeting HSP90/survivin using a cell permeable structure based peptido-mimetic shepherdin in retinoblastoma
Author(s) Venkatesan, Nalini
Kanwar, Jagat R.ORCID iD for Kanwar, Jagat R.
Deepa, Perinkulam Ravi
Navaneethakrishnan, Saranya
Joseph, Chitra
Krishnakumar, Subramanian
Journal name Chemico-biological interactions
Volume number 252
Start page 141
End page 149
Total pages 9
Publisher Elsevier
Place of publication London, Eng.
Publication date 2016-05
ISSN 1872-7786
Keyword(s) Heat shock proteins
Peptido-mimetic (shepherdin)
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Pharmacology & Pharmacy
Summary 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 μg/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.
Language eng
DOI 10.1016/j.cbi.2016.04.011
Field of Research 119999 Medical and Health Sciences not elsewhere classified
0601 Biochemistry And Cell Biology
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Elsevier
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Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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