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Article

P-gp upregulation may be blocked by natural curcuminoids, a novel class of chemoresistance-preventing agent

  • Authors:
    • Dong Xu
    • Wei Tian
    • Hong Shen
  • View Affiliations / Copyright

    Affiliations: Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang 310009, P.R. China, Cancer Institute (The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang 310009, P.R. China, Department of Medical Oncology, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang 310009, P.R. China
  • Pages: 115-121
    |
    Published online on: September 27, 2012
       https://doi.org/10.3892/mmr.2012.1106
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Abstract

Once multidrug resistance (MDR) occurs in cancer cells, it is very difficult to reverse since overexpression of P-glycoprotein (P-gp) is accompanied by altered expression of numerous other activated target genes. Previously, we reported that curcumin pretreatment would be an ideal method to prevent acquired drug resistance induced by adriamycin, administered prior to the development of MDR. To further confirm the previous results, we examined the potency of 3 forms of curcuminoids present in turmeric as potent preventers of acquired drug resistance. K562 cells were pretreated with or without curcuminoids for 24 h and co-incubated with adriamycin. P-gp and mdr1 mRNA levels were analyzed separately by flow cytometry and quantitative real-time RT-PCR. In addition, we performed an MTT assay to determine the adriamycin-induced cytotoxicity with or without pretreatment with curcuminoids. Short- and long-term exposure of native K562 cells to adriamycin led to upregulation of P-gp and formation of acquired drug resistance. However, after pretreatment with curcuminoids, the above processes were significantly inhibited. The MTT assay examined the enhanced effect of curcuminoids on adriamycin‑induced cytotoxicity. Results from western blotting showed that curcuminoids could inhibit the adriamycin-induced increase of NF-κB nuclear translocation and activation. Finally, under the long-term exposure model, we proved that curcumin was capable of blocking the occurrence of MDR in the cell line throughout the 56-day culture period. This study reveals that curcuminoids have the potency to block the upregulation of P-gp and its mRNA induced by short- and long-term exposure to adriamycin. Curcuminoids may be a novel class of potent chemoresistance-preventing agent with high safety and the potential for widespread clinical use.
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1 

Cole SP, Bhardwaj G, Gerlach JH, et al: Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 258:1650–1654. 1992. View Article : Google Scholar : PubMed/NCBI

2 

Gottesman MM, Fojo T and Bates SE: Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer. 2:48–58. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Schinkel AH and Jonker JW: Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev. 55:3–29. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Xu D, Lu Q and Hu X: Down-regulation of P-glycoprotein expression in MDR breast cancer cell MCF-7/ADR by honokiol. Cancer Lett. 243:274–280. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Pan Q, Lu Q, Zhang K and Hu X: Dibenzocyclooctadiene lingnans: a class of novel inhibitors of P-glycoprotein. Cancer Chemother Pharmacol. 58:99–106. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Sun M, Xu X, Lu Q, Pan Q and Hu X: Schisandrin B: a dual inhibitor of P-glycoprotein and multidrug resistance-associated protein 1. Cancer Lett. 246:300–307. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Sakaeda T, Nakamura T, Hirai M, et al: MDR1 up-regulated by apoptotic stimuli suppresses apoptotic signaling. Pharm Res. 19:1323–1329. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Gottesman MM and Ling V: The molecular basis of multidrug resistance in cancer: the early years of P-glycoprotein research. FEBS Lett. 580:998–1009. 2006.PubMed/NCBI

9 

Xu DTW and Shen H: Curcumin prevents induced drug resistance: a novel function? Chin J Cancer Res. 23:218–223. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Schiedlmeier B, Kuhlcke K, Eckert HG, Baum C, Zeller WJ and Fruehauf S: Quantitative assessment of retroviral transfer of the human multidrug resistance 1 gene to human mobilized peripheral blood progenitor cells engrafted in nonobese diabetic/severe combined immunodeficient mice. Blood. 95:1237–1248. 2000.

11 

Cocker HA, Tiffin N, Pritchard-Jones K, Pinkerton CR and Kelland LR: In vitro prevention of the emergence of multidrug resistance in a pediatric rhabdomyosarcoma cell line. Clin Cancer Res. 7:3193–3198. 2001.PubMed/NCBI

12 

Shen H, Xu W, Chen Q, Wu Z, Tang H and Wang F: Tetrandrine prevents acquired drug resistance of K562 cells through inhibition of mdr1 gene transcription. J Cancer Res Clin Oncol. 136:659–665. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Yague E, Armesilla AL, Harrison G, et al: P-glycoprotein (MDR1) expression in leukemic cells is regulated at two distinct steps, mRNA stabilization and translational initiation. J Biol Chem. 278:10344–10352. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Hu XF, Slater A, Wall DM, Parkin JD, Kantharidis P and Zalcberg JR: Cyclosporin A and PSC 833 prevent up-regulation of MDR1 expression by anthracyclines in a human multidrug-resistant cell line. Clin Cancer Res. 2:713–720. 1996.PubMed/NCBI

15 

Su CC, Lin JG, Li TM, et al: Curcumin-induced apoptosis of human colon cancer colo 205 cells through the production of ROS, Ca2+ and the activation of caspase-3. Anticancer Res. 26:4379–4389. 2006.PubMed/NCBI

16 

Lin YG, Kunnumakkara AB, Nair A, et al: Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-kappaB pathway. Clin Cancer Res. 13:3423–3430. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Yodkeeree S, Chaiwangyen W, Garbisa S and Limtrakul P: Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA. J Nutr Biochem. 20:87–95. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Tamvakopoulos C, Dimas K, Sofianos ZD, et al: Metabolism and anticancer activity of the curcumin analogue, dimethoxycurcumin. Clin Cancer Res. 13:1269–1277. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Anuchapreeda S, Leechanachai P, Smith MM, Ambudkar SV and Limtrakul PN: Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells. Biochem Pharmacol. 64:573–582. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Limtrakul P, Anuchapreeda S and Buddhasukh D: Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids. BMC Cancer. 4:132004. View Article : Google Scholar : PubMed/NCBI

21 

Chearwae W, Wu CP, Chu HY, Lee TR, Ambudkar SV and Limtrakul P: Curcuminoids purified from turmeric powder modulate the function of human multidrug resistance protein 1 (ABCC1). Cancer Chemother Pharmacol. 57:376–388. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Li Y, Revalde JL, Reid G and Paxton JW: Modulatory effects of curcumin on multi-drug resistance-associated protein 5 in pancreatic cancer cells. Cancer Chemother Pharmacol. 68:603–610. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Egashira M, Kawamata N, Sugimoto K, Kaneko T and Oshimi K: P-glycoprotein expression on normal and abnormally expanded natural killer cells and inhibition of P-glycoprotein function by cyclosporin A and its analogue, PSC833. Blood. 93:599–606. 1999.PubMed/NCBI

24 

Su CC, Chen GW, Lin JG, Wu LT and Chung JG: Curcumin inhibits cell migration of human colon cancer colo 205 cells through the inhibition of nuclear factor kappa B/p65 and down-regulates cyclooxygenase-2 and matrix metalloproteinase-2 expressions. Anticancer Res. 26:1281–1288. 2006.

25 

Amiri KI and Richmond A: Role of nuclear factor-kappa B in melanoma. Cancer Metastasis Rev. 24:301–313. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J and Aggarwal BB: Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res. 67:3853–3861. 2007. View Article : Google Scholar

27 

Ahsan H, Parveen N, Khan NU and Hadi SM: Pro-oxidant, anti-oxidant and cleavage activities on DNA of curcumin and its derivatives demethoxycurcumin and bisdemethoxycurcumin. Chem Biol Interact. 121:161–175. 1999. View Article : Google Scholar : PubMed/NCBI

28 

Sandur SK, Pandey MK, Sung B, et al: Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis. 28:1765–1773. 2007. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Xu D, Tian W and Shen H: P-gp upregulation may be blocked by natural curcuminoids, a novel class of chemoresistance-preventing agent. Mol Med Rep 7: 115-121, 2013.
APA
Xu, D., Tian, W., & Shen, H. (2013). P-gp upregulation may be blocked by natural curcuminoids, a novel class of chemoresistance-preventing agent. Molecular Medicine Reports, 7, 115-121. https://doi.org/10.3892/mmr.2012.1106
MLA
Xu, D., Tian, W., Shen, H."P-gp upregulation may be blocked by natural curcuminoids, a novel class of chemoresistance-preventing agent". Molecular Medicine Reports 7.1 (2013): 115-121.
Chicago
Xu, D., Tian, W., Shen, H."P-gp upregulation may be blocked by natural curcuminoids, a novel class of chemoresistance-preventing agent". Molecular Medicine Reports 7, no. 1 (2013): 115-121. https://doi.org/10.3892/mmr.2012.1106
Copy and paste a formatted citation
x
Spandidos Publications style
Xu D, Tian W and Shen H: P-gp upregulation may be blocked by natural curcuminoids, a novel class of chemoresistance-preventing agent. Mol Med Rep 7: 115-121, 2013.
APA
Xu, D., Tian, W., & Shen, H. (2013). P-gp upregulation may be blocked by natural curcuminoids, a novel class of chemoresistance-preventing agent. Molecular Medicine Reports, 7, 115-121. https://doi.org/10.3892/mmr.2012.1106
MLA
Xu, D., Tian, W., Shen, H."P-gp upregulation may be blocked by natural curcuminoids, a novel class of chemoresistance-preventing agent". Molecular Medicine Reports 7.1 (2013): 115-121.
Chicago
Xu, D., Tian, W., Shen, H."P-gp upregulation may be blocked by natural curcuminoids, a novel class of chemoresistance-preventing agent". Molecular Medicine Reports 7, no. 1 (2013): 115-121. https://doi.org/10.3892/mmr.2012.1106
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