PMID- 18503584
OWN - NLM
STAT- MEDLINE
DCOM- 20081216
LR  - 20211020
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 142
IP  - 4
DP  - 2008 Aug
TI  - HSP70 inhibition reverses cell adhesion mediated and acquired drug resistance in 
      multiple myeloma.
PG  - 551-61
LID - 10.1111/j.1365-2141.2008.07217.x [doi]
AB  - Heat shock proteins (HSPs) are a super family of highly conserved molecular 
      chaperone proteins, which are induced in response to stress. HSP70 has been 
      demonstrated to inhibit apoptosis induced by a number of chemotherapeutic agents. 
      Previous investigations have suggested the development of drug resistance in 
      multiple myeloma (MM) cells after adhesion to stroma. This study used MM cell 
      lines and primary plasma cells to determine if HSP70 had a role in development of 
      chemo resistance. Adhesion of MM cells to either bone marrow stromal cells or 
      fibronectin (FN) enhanced HSP70 expression. Inhibition of the HSP70 expression 
      decreased 8226 cell adhesion to stroma or FN and induced more apoptosis in 
      FN-adhered 8226 cells than in suspension cultures at 24 h. Further, HSP70 
      inhibitors enhanced melphalan-induced apoptosis and reversed melphalan-induced 
      cell adhesion-mediated drug resistance (CAM-DR) phenotype. In addition, compared 
      to parental cells, KNK-437, a heat shock factor inhibitor caused more apoptosis 
      in melphalan-resistant 8226/LR5 cells and sensitized them to melphalan. Primary 
      CD138 positive cells showed high expression of HSPA4 mRNA, and KNK-437 caused 
      apoptosis in these cells. In conclusion, our data suggest inhibition of HSP70, 
      reduced adhesion and caused apoptosis of both acquired and de novo drug resistant 
      MM cells.
FAU - Nimmanapalli, Ramadevi
AU  - Nimmanapalli R
AD  - Department of Pathobiology, College of Veterinary Medicine, Tuskegee University, 
      Tuskegee, AL 36088, USA. ramadevi.nimmanapalli@gmail.com
FAU - Gerbino, Elvira
AU  - Gerbino E
FAU - Dalton, William S
AU  - Dalton WS
FAU - Gandhi, Varsha
AU  - Gandhi V
FAU - Alsina, Melissa
AU  - Alsina M
LA  - eng
GR  - R01 CA077859/CA/NCI NIH HHS/United States
GR  - R01 CA077859-10/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080522
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Fibronectins)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - Q41OR9510P (Melphalan)
SB  - IM
MH  - Antineoplastic Agents, Alkylating/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Adhesion
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Drug Resistance, Neoplasm/*physiology
MH  - Fibronectins/metabolism
MH  - HSP70 Heat-Shock Proteins/*antagonists & inhibitors
MH  - Humans
MH  - Melphalan/*pharmacology
MH  - Multiple Myeloma/drug therapy/*metabolism
MH  - Plasma Cells/drug effects/metabolism
PMC - PMC4503206
MID - NIHMS92552
EDAT- 2008/05/28 09:00
MHDA- 2008/12/17 09:00
PMCR- 2015/07/15
CRDT- 2008/05/28 09:00
PHST- 2008/05/28 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/05/28 09:00 [entrez]
PHST- 2015/07/15 00:00 [pmc-release]
AID - BJH7217 [pii]
AID - 10.1111/j.1365-2141.2008.07217.x [doi]
PST - ppublish
SO  - Br J Haematol. 2008 Aug;142(4):551-61. doi: 10.1111/j.1365-2141.2008.07217.x. 
      Epub 2008 May 22.