Hsp60 and IL-8 axis promotes apoptosis resistance in cancer.

Abstract

BACKGROUND:

Interleukin-8 (IL-8) and heat shock protein 60 (Hsp60) play crucial roles in cell survival and maintenance of cellular homoeostasis. However, cross talks between these two proteins are not defined.

METHODS:

IL-8 expression in tumour tissue sections was analysed by immunohistochemistry. IL-8 expression and release in cancer cells was quantified using enzyme-linked immunosorbent assay (ELISA). Apoptosis was quantified using caspase activity and Annexin-V/PI staining.

RESULTS:

We observed IL-8 release from cancer cells in response to histone deacetylase inhibitor, apicidin (Api), and non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase, thapsigargin (TG). IL-8 release was increased upon TG-treatment. TG-induced IL-8 expression was reduced in the presence of Api in Bax-dependent manner. Increased apoptosis was associated with decreased IL-8 expression in response to combined treatment of TG and Api. TG and Api combination induced caspase-8 and caspase-9 dependent apoptosis. Hsp60 knockdown abrogated IL-8 expression induced by Api, TG, and their combination. The level of TGF-β, an upstream regulator of IL-8, was decreased upon Hsp60-silencing. Knocking down Hsp60 decreased IL-8 expression and its release in prostate cancer cell xenograft tumours in SCID mice.

CONCLUSION:

This study describes the underlying mechanism associated with apoptosis resistance mediated via Hsp60-IL-8 axis in cancer.

• Authors: Sandeep Kumar, Jordan O'Malley, Ajay Kumar Chaudhary, Joseph R Inigo, Neelu Yadav, Rahul Kumar, Dhyan Chandra
• Journal: British journal of cancer (Br J Cancer) Vol. 121 Issue 11 Pg. 934-943 (11 2019) ISSN: 1532-1827 [Electronic] England
• PMID: 31673102 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CXCL8 protein, human
• Chaperonin 60
• HSPD1 protein, human
• Interleukin-8
• Mitochondrial Proteins
• Peptides, Cyclic
• apicidin
• Thapsigargin
• CASP8 protein, human
• CASP9 protein, human
• Caspase 8
• Caspase 9

Topics

• Animals
• Apoptosis (drug effects)
• Caspase 8 (genetics)
• Caspase 9 (genetics)
• Chaperonin 60 (genetics, metabolism)
• Gene Knockdown Techniques
• HCT116 Cells
• Heterografts
• Humans
• Interleukin-8 (genetics, metabolism)
• Male
• Mice
• Mice, SCID
• Mitochondrial Proteins (genetics, metabolism)
• Neoplasms (metabolism, pathology)
• PC-3 Cells
• Peptides, Cyclic (pharmacology)
• Signal Transduction (drug effects)
• Thapsigargin (pharmacology)