Iron alters Ca2+ homeostasis in doxorubicin-resistant K562 cells

Yalcintepe L., Erdag D., AKBAŞ F., Kucukkaya B.

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, vol.47, no.7, pp.1221-1230, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 47 Issue: 7
  • Publication Date: 2020
  • Doi Number: 10.1111/1440-1681.13295
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, SportDiscus, Veterinary Science Database
  • Page Numbers: pp.1221-1230
  • Istanbul University Affiliated: Yes


Iron is an essential trace element especially in cell proliferation, and growth for various cellular events. An increasing amount of research has shown that iron metabolism is altered in tumour cells which usually have rapid growth rates. However, the number of studies on iron metabolism, and calcium regulation are limited in drug-resistant tumour cells. Previously, we have shown that modulation of iron metabolism through iron chelation regulated the intracellular calcium, and increased the doxorubicin sensitivity. In the present study, we investigated the effects of iron on mRNA expression profiles of fifteen key genes (IP(3)R1/2/3, RYR1/2, SERCA1/2/3, NCX1/2/3, PMCA1/2/3, and PMCA4) related to calcium homeostasis in the parental cell line K562 and its subclone doxorubicin-resistant K562 cells. According to the Delta Delta Ct method with a two-fold expression difference (P < .05) as a cut-off level, although iron showed differential effects on most of the genes, IP3R and PMCA genes were especially determined to have changed significantly. These results show that iron metabolism is an important metabolism due to changes in the expression of genes involved in calcium regulation and is a new perspective to overcome cancer/drug resistance.