PMID- 31673102
OWN - NLM
STAT- MEDLINE
DCOM- 20200619
LR  - 20220204
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 121
IP  - 11
DP  - 2019 Nov
TI  - Hsp60 and IL-8 axis promotes apoptosis resistance in cancer.
PG  - 934-943
LID - 10.1038/s41416-019-0617-0 [doi]
AB  - 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 Ca(2+) 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-beta, 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.
FAU - Kumar, Sandeep
AU  - Kumar S
AD  - Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, USA.
AD  - Department of Surgery, Division of Surgical Oncology, University of Illinois at 
      Chicago, Chicago, IL, 60612, USA.
FAU - O'Malley, Jordan
AU  - O'Malley J
AD  - Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, USA.
FAU - Chaudhary, Ajay Kumar
AU  - Chaudhary AK
AD  - Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, USA.
FAU - Inigo, Joseph R
AU  - Inigo JR
AD  - Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, USA.
FAU - Yadav, Neelu
AU  - Yadav N
AD  - Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, USA.
FAU - Kumar, Rahul
AU  - Kumar R
AD  - Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, USA.
FAU - Chandra, Dhyan
AU  - Chandra D
AD  - Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer 
      Center, Buffalo, NY, USA. dhyan.chandra@roswellpark.org.
LA  - eng
GR  - P30 CA016056/CA/NCI NIH HHS/United States
GR  - RO1-CA160685/U.S. Department of Health & Human Services | National Institutes 
      of Health (NIH)/International
GR  - P30-CA016056/U.S. Department of Health & Human Services | National Institutes 
      of Health (NIH)/International
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191101
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Chaperonin 60)
RN  - 0 (HSPD1 protein, human)
RN  - 0 (Interleukin-8)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (apicidin)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (CASP9 protein, human)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Caspase 8/genetics
MH  - Caspase 9/genetics
MH  - Chaperonin 60/genetics/*metabolism
MH  - Gene Knockdown Techniques
MH  - HCT116 Cells
MH  - Heterografts
MH  - Humans
MH  - Interleukin-8/genetics/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Mitochondrial Proteins/genetics/*metabolism
MH  - Neoplasms/*metabolism/pathology
MH  - PC-3 Cells
MH  - Peptides, Cyclic/pharmacology
MH  - Signal Transduction/drug effects
MH  - Thapsigargin/pharmacology
PMC - PMC6889399
COIS- The authors declare no competing interests.
EDAT- 2019/11/02 06:00
MHDA- 2020/06/20 06:00
PMCR- 2020/11/01
CRDT- 2019/11/02 06:00
PHST- 2019/07/26 00:00 [received]
PHST- 2019/10/08 00:00 [accepted]
PHST- 2019/09/21 00:00 [revised]
PHST- 2019/11/02 06:00 [pubmed]
PHST- 2020/06/20 06:00 [medline]
PHST- 2019/11/02 06:00 [entrez]
PHST- 2020/11/01 00:00 [pmc-release]
AID - 10.1038/s41416-019-0617-0 [pii]
AID - 617 [pii]
AID - 10.1038/s41416-019-0617-0 [doi]
PST - ppublish
SO  - Br J Cancer. 2019 Nov;121(11):934-943. doi: 10.1038/s41416-019-0617-0. Epub 2019 
      Nov 1.