Top

Cancer Chemotherapy and Pharmacology

Published in:

01-10-2013 | Original Article

Inhibition of sorcin reverses multidrug resistance of K562/A02 cells and MCF-7/A02 cells via regulating apoptosis-related proteins

Authors: Yunhui Hu, Xin Cheng, Shuangjing Li, Yuan Zhou, Jianxiang Wang, Tao Cheng, Ming Yang, Dongsheng Xiong

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2013

Abstract

Purpose

Sorcin, a 22-kDa calcium-binding protein, renders cancer cells resistant to chemotherapeutic agents, thus playing an important role in multidrug resistance (MDR). But the mechanisms mediated by sorcin still remain quite elusive. This study aim to explore whether sorcin silencing could restore chemosensitivity in MDR cancer cells and seek to identify the functional mechanisms mediated by sorcin.

Methods

To investigate the mechanisms of sorcin-silencing-induced chemosensitivity, transient expression of sorcin-siRNAs was performed in doxorubicin-induced MDR cell lines, K562/A02 and MCF-7/A02. Sensitivity to five chemotherapeutic agents was evaluated by analysis of cell survival and cell apoptosis.

Results

In this report, we show that down-regulation of sorcin did not alter expression or function of P-gp, but actually induced cell apoptosis and chemosensitivity in K562/A02 and MCF-7/A02. We also observe that silencing of sorcin-enhanced chemotherapeutic agent effects partly through regulating apoptosis-related protein, including Bcl-2, Bax, c-jun and c-fos.

Conclusion

This offers the rationale for the development of therapeutic strategies down-regulating sorcin expression for the treatment of cancer, especially for the reversal of MDR.

Gottesman MM, Fojo T, Bates SE (2002) Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2(1):48–58PubMedCrossRef

Steinbach D, Legrand O (2007) ABC transporters and drug resistance in leukemia: was P-gp nothing but the first head of the Hydra? Leukemia 21(6):1172–1176PubMedCrossRef

Liu F et al (2008) Co-expression of cytokeratin 8 and breast cancer resistant protein indicates a multifactorial drug-resistant phenotype in human breast cancer cell line. Life Sci 83(13–14):496–501PubMedCrossRef

Wang CH et al (2009) Effects of non-cytotoxic drugs on the growth of multidrug-resistance human gastric carcinoma cell line. J Dig Dis 10(2):91–98PubMedCrossRef

Zhao LJ et al (2012) Modulation of drug resistance in ovarian cancer cells by inhibition of protein kinase C-alpha (PKC-alpha) with small interference RNA (siRNA) agents. Asian Pac J Cancer Prev 13(8):3631–3636PubMedCrossRef

Ye CG et al (2011) Indomethacin and SC236 enhance the cytotoxicity of doxorubicin in human hepatocellular carcinoma cells via inhibiting P-glycoprotein and MRP1 expression. Cancer Lett 304(2):90–96PubMedCrossRef

Pu J, Lou F, Zhou Q (1999) In vitro reversal effect of cyclosporin A in combination with cytokines on multidrug resistant cell line K562/A02. Zhonghua Yi Xue Za Zhi 79(3):224–226PubMed

Meyers MB et al (1995) Association of sorcin with the cardiac ryanodine receptor. J Biol Chem 270(44):26411–26418PubMedCrossRef

Hamada H et al (1988) Purification of the Mr 22,000 calcium-binding protein (sorcin) associated with multidrug resistance and its detection with monoclonal antibodies. Cancer Res 48(11):3173–3178PubMed

10.

Roberts D et al (1989) Association of sorcin with drug resistance in L1210 cells. Cancer Chemother Pharmacol 23(1):19–25PubMedCrossRef

11.

Parekh HK et al (2002) Overexpression of sorcin, a calcium-binding protein, induces a low level of paclitaxel resistance in human ovarian and breast cancer cells. Biochem Pharmacol 63(6):1149–1158PubMedCrossRef

12.

He QC, Zhang GY, Cao WJ (2008) Correlation of sorcin overexpression to multidrug resistance of human gastric cancer cell line SGC7901. Ai Zheng 27(4):337–342PubMed

13.

Qu Y et al (2010) Comparative proteomic profiling identified sorcin being associated with gemcitabine resistance in non-small cell lung cancer. Med Oncol 27(4):1303–1308PubMedCrossRef

14.

Nagpal JK, Das BR (2007) Identification of differentially expressed genes in tobacco chewing-mediated oral cancer by differential display-polymerase chain reaction. Eur J Clin Invest 37(8):658–664PubMedCrossRef

15.

Tan Y et al (2003) Expression of sorcin predicts poor outcome in acute myeloid leukemia. Leuk Res 27(2):125–131PubMedCrossRef

16.

Zhou Y et al (2006) Sorcin, an important gene associated with multidrug-resistance in human leukemia cells. Leuk Res 30(4):469–476PubMedCrossRef

17.

Yang CZ et al (1995) Multidrug resistance in leukemic cell line K562/A02 induced by doxorubicin. Zhongguo Yao Li Xue Bao 16(4):333–337PubMed

18.

Shi R et al (2011) A novel indirubin derivative PHII-7 potentiates adriamycin cytotoxicity via inhibiting P-glycoprotein expression in human breast cancer MCF-7/ADR cells. Eur J Pharmacol 669(1–3):38–44PubMedCrossRef

19.

Batist G et al (1986) Overexpression of a novel anionic glutathione transferase in multidrug-resistant human breast cancer cells. J Biol Chem 261(33):15544–15549PubMed

20.

Qi J et al (2002) Function and mechanism of pyronaridine: a new inhibitor of P-glycoprotein-mediated multidrug resistance. Acta Pharmacol Sin 23(6):544–550PubMed

21.

Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1–2):55–63PubMedCrossRef

22.

Yague E et al (2003) P-glycoprotein (MDR1) expression in leukemic cells is regulated at two distinct steps, mRNA stabilization and translational initiation. J Biol Chem 278(12):10344–10352PubMedCrossRef

23.

Hwang M, Moretti L, Lu B (2009) HSP90 inhibitors: multi-targeted antitumor effects and novel combinatorial therapeutic approaches in cancer therapy. Curr Med Chem 16(24):3081–3092PubMedCrossRef

24.

Kellner U et al (1997) Decreased drug accumulation in a mitoxantrone-resistant gastric carcinoma cell line in the absence of P-glycoprotein. Int J Cancer 71(5):817–824PubMedCrossRef

25.

Beyer-Sehlmeyer G et al (1999) Suppressive subtractive hybridisation reveals differential expression of serglycin, sorcin, bone marrow proteoglycan and prostate-tumour-inducing gene I (PTI-1) in drug-resistant and sensitive tumour cell lines of haematopoetic origin. Eur J Cancer 35(12):1735–1742PubMedCrossRef

26.

Kawakami M et al (2007) Knock-down of sorcin induces up-regulation of MDR1 in HeLa cells. Biol Pharm Bull 30(6):1065–1073PubMedCrossRef

27.

Wang SL et al (1995) Isolation and molecular cloning of human sorcin a calcium-binding protein in vincristine-resistant HOB1 lymphoma cells. Biochim Biophys Acta 1260(3):285–293PubMedCrossRef

28.

Lee WP (1996) Purification, cDNA cloning, and expression of human sorcin in vincristine-resistant HOB1 lymphoma cell lines. Arch Biochem Biophys 325(2):217–226PubMedCrossRef

29.

Landriscina M et al (2010) Mitochondrial chaperone Trap1 and the calcium binding protein sorcin interact and protect cells against apoptosis induced by antiblastic agents. Cancer Res 70(16):6577–6586PubMedCrossRef

30.

Mikula M et al (2003) The proto-oncoprotein c-Fos negatively regulates hepatocellular tumorigenesis. Oncogene 22(43):6725–6738PubMedCrossRef

31.

Herrlich P (2001) Cross-talk between glucocorticoid receptor and AP-1. Oncogene 20(19):2465–2475PubMedCrossRef

32.

Deng L et al (2010) Upregulation of soluble resistance-related calcium-binding protein (sorcin) in gastric cancer. Med Oncol 27(4):1102–1108PubMedCrossRef

33.

Maddalena F et al (2013) Resistance to paclitxel in breast carcinoma cells requires a quality control of mitochondrial antiapoptotic proteins by TRAP1. Mol Oncol. pii: S1574-7891(13)00079-3

34.

Diaz-Blanco E et al (2007) Molecular signature of CD34(+) hematopoietic stem and progenitor cells of patients with CML in chronic phase. Leukemia 21(3):494–504PubMedCrossRef

Title: Inhibition of sorcin reverses multidrug resistance of K562/A02 cells and MCF-7/A02 cells via regulating apoptosis-related proteins
Authors: Yunhui Hu
Xin Cheng
Shuangjing Li
Yuan Zhou
Jianxiang Wang
Tao Cheng
Ming Yang
Dongsheng Xiong
Publication date: 01-10-2013
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2013
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-013-2254-2

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 4/2013

A phase I/II study of carfilzomib 2–10-min infusion in patients with advanced solid tumors

Antitumor efficacy, toxicity and pharmacokinetics of 9-nitrocamptothecin: role of lactone ratio

Pharmacogenetic determinants associated with sunitinib-induced toxicity and ethnic difference in Korean metastatic renal cell carcinoma patients

A phase II study of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy followed by surgery and adjuvant S-1 chemotherapy in potentially resectable gastric or gastroesophageal junction adenocarcinoma

Identification of two novel inhibitors of mTOR signaling pathway based on high content screening

Effects of pemetrexed, gefitinib, and their combination on human colorectal cancer cells

Keynote webinar | Spotlight on antibody–drug conjugates in cancer