search button
Open Access

Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium‑binding protein A8 and P‑glycoprotein

  • Authors:
    • Liu Yang
    • Duo Li
    • Peiyan Tang
    • Yunfei Zuo

  • View Affiliations

  • Published online on: November 13, 2019     https://doi.org/10.3892/ol.2019.11083
  • Pages: 83-92

  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The development of multidrug resistance (MDR) has seriously impeded the efficacy of drug treatment of chronic myeloid leukemia (CML). Recent studies have indicated that S100 calcium‑binding protein A8 (S100A8) is associated with the occurrence and development of MDR. Traditional Chinese medicine may provide drugs with the potential to be used as multidrug resistance reversal agents with low toxicity and multi‑target characteristics. The present study selected K562/DOX cells, a CML drug‑resistant cell line, as a research model, and aimed to examine whether curcumin was able to reverse the resistance to doxorubicin (DOX), and elucidate the underlying molecular mechanisms. An MTT cytotoxicity assay indicated that curcumin at 0.5‑2 µM reversed DOX resistance with a reversal index of 1.3‑9.3. Western blot analysis revealed that curcumin treatment caused a downregulation of the expression of P‑glycoprotein (P‑gp) and S100A8 in a dose‑ and time‑dependent manner. To study the internal association between S100A8 and P‑gp, and the S100A8 role in drug resistance reversal, an RNA knockdown assay was conducted; however, S100A8 did not regulate the expression of P‑gp or vice versa. After inhibiting the expression of S100A8 with specific small interfering RNA (si‑S100A8), the sensitivity of K562/DOX cells to DOX was enhanced. In addition, si‑S100A8 did not increase the intracellular accumulation of DOX, but increased the intracellular free calcium ion content, and the expression and activity of apoptosis‑associated proteins, thereby inducing apoptosis. In conclusion, the present study suggested that inhibition of S100A8 expression increased DOX‑induced apoptosis, and curcumin acted independently on S100A8 and P‑gp to exert its drug resistance reversal effects.
View Figures
View References

Related Articles

Journal Cover

January-2020
Volume 19 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

  • Journal Metrics
  • Impact Factor: 2.9
  • Ranked Oncology
    (total number of cites)
  • CiteScore: 6.3
  • CiteScore Rank: Q2: #119/366 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.725
  • SCImago Journal Rank (SJR): 0.639
International Symposium on Molecular Medicine Conference Banner
The Cancer Story
World Congress on Advances in Oncology and International Symposium on Molecular Medicine Conference Banner
World Academy Of Sciences Banner
Heyday Road Banner

0

Copy and paste a formatted citation
x
Spandidos Publications style
Yang L, Li D, Tang P and Zuo Y: Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium‑binding protein A8 and P‑glycoprotein. Oncol Lett 19: 83-92, 2020
APA
Yang, L., Li, D., Tang, P., & Zuo, Y. (2020). Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium‑binding protein A8 and P‑glycoprotein. Oncology Letters, 19, 83-92. https://doi.org/10.3892/ol.2019.11083
MLA
Yang, L., Li, D., Tang, P., Zuo, Y."Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium‑binding protein A8 and P‑glycoprotein". Oncology Letters 19.1 (2020): 83-92.
Chicago
Yang, L., Li, D., Tang, P., Zuo, Y."Curcumin increases the sensitivity of K562/DOX cells to doxorubicin by targeting S100 calcium‑binding protein A8 and P‑glycoprotein". Oncology Letters 19, no. 1 (2020): 83-92. https://doi.org/10.3892/ol.2019.11083