Chemosensitisation of Spontaneous Multidrug Resistance by a 1,4-dihydropyridine Analogue and Verapamil in Human Glioma Cell Lines Overexpressing MRP or MDR1

Overview

Journal Br J Cancer

Specialty Oncology

Date 1995 Aug 1

PMID 7640227

Citations 17

Authors

T Abe

K Koike

T Ohga

T Kubo

M Wada

K Kohno

T Mori

K Hidaka

M Kuwano

Affiliations

Soon will be listed here.

Abstract

Multidrug resistance phenotypes in human tumours are associated with the overexpression of the 170 kDa P-glycoprotein encoded by the multidrug resistance 1 (MDR1) gene, and also with that of the non-P-glycoprotein-mediated multidrug resistance gene, MRP, which encodes a 190 kDa membrane ATP-binding protein. We have previously reported that overexpression of MRP appears to be responsible for spontaneous multidrug resistance in some human glioma cell lines (Abe et al., Int. J. Cancer, 58, 860-864, 1994). In this study, we investigated whether chemosensitising agents of P-glycoprotein-mediated multidrug resistance such as verapamil, a biscoclaurine alkaloid (cepharanthine), and a dihydropyridine analogue (NIK250) could also reverse multidrug resistance in human glioma cells. The glioma cell lines were the two MRP-expressing cell lines, T98G and IN500, an MDR1-expressing cell line, CCF-STTG1, and the MRP1 MDR1-non-expressing cell line, IN157. Verapamil and NIK250 almost completely reversed drug resistance to vincristine, etoposide and doxorubicin in T98G cells, while they also reversed drug resistance to vincristine and etoposide, but only partially to doxorubicin in IN500 cells. Cepharanthine as well as verapamil and NIK250 reversed vincristine resistance in CCF-STTG1 cells, but cepharanthine only partially reversed drug resistance in T98G and IN500 cells. The cellular accumulation of [3H]etoposide increased about 2- and 3-fold compared with control in T98G cells in the presence of verapamil and NIK250 respectively. Furthermore, the release of doxorubicin from the nuclei of T98G cells was blocked by NIK250. However, NIK250 and verapamil caused no apparent increase in vincristine accumulation in T98G cells. NIK250 or verapamil might exert inhibitory effects upon MRP function, resulting in a reversal of MRP-mediated spontaneous multidrug resistance in cultured human glioma cells.

Citing Articles

Pharmacological Activity of Cepharanthine.

Liu K, Hong B, Wang S, Lou F, You Y, Hu R Molecules. 2023; 28(13).

PMID: 37446681 PMC: 10343550. DOI: 10.3390/molecules28135019.

Effect of Polyunsaturated Fatty Acids on Temozolomide Drug-Sensitive and Drug-Resistant Glioblastoma Cells.

Silva J, Colquhoun A Biomedicines. 2023; 11(3).

PMID: 36979758 PMC: 10045395. DOI: 10.3390/biomedicines11030779.

Insights into an Immunotherapeutic Approach to Combat Multidrug Resistance in Hepatocellular Carcinoma.

Devan A, Kumar A, Nair B, Anto N, Muraleedharan A, Mathew B Pharmaceuticals (Basel). 2021; 14(7).

PMID: 34358082 PMC: 8308499. DOI: 10.3390/ph14070656.

Testing of the Survivin Suppressant YM155 in a Large Panel of Drug-Resistant Neuroblastoma Cell Lines.

Michaelis M, Voges Y, Rothweiler F, Weipert F, Zia-Ahmad A, Cinatl J Cancers (Basel). 2020; 12(3).

PMID: 32131402 PMC: 7139505. DOI: 10.3390/cancers12030577.

Cell Migration Related to MDR-Another Impediment to Effective Chemotherapy?.

Kryczka J, Boncela J Molecules. 2018; 23(2).

PMID: 29401721 PMC: 6017720. DOI: 10.3390/molecules23020331.

References

Watanabe Y, Takano H, Kiue A, Kohno K, Kuwano M . Potentiation of etoposide and vincristine by two synthetic 1,4-dihydropyridine derivatives in multidrug-resistant and atypical multidrug-resistant human cancer cells. Anticancer Drug Des. 1991; 6(1):47-57. View

Kiue A, Sano T, Naito A, Inada H, Suzuki K, Okumura M . Reversal by two dihydropyridine compounds of resistance to multiple anticancer agents in mouse P388 leukemia in vivo and in vitro. Jpn J Cancer Res. 1990; 81(10):1057-64. PMC: 5917977. DOI: 10.1111/j.1349-7006.1990.tb03346.x. View

Meijer C, Mulder N, Timmer-Bosscha H, Peters W, De Vries E . Combined in vitro modulation of adriamycin resistance. Int J Cancer. 1991; 49(4):582-6. DOI: 10.1002/ijc.2910490419. View

Cole S, Bhardwaj G, Gerlach J, MACKIE J, Grant C, Almquist K . Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 1992; 258(5088):1650-4. DOI: 10.1126/science.1360704. View

Zaman G, Versantvoort C, Smit J, Eijdems E, de Haas M, Smith A . Analysis of the expression of MRP, the gene for a new putative transmembrane drug transporter, in human multidrug resistant lung cancer cell lines. Cancer Res. 1993; 53(8):1747-50. View

Abe T, Okamura K, Ono M, Kohno K, Mori T, Hori S . Induction of vascular endothelial tubular morphogenesis by human glioma cells. A model system for tumor angiogenesis. J Clin Invest. 1993; 92(1):54-61. PMC: 293529. DOI: 10.1172/JCI116599. View

Krishnamachary N, CENTER M . The MRP gene associated with a non-P-glycoprotein multidrug resistance encodes a 190-kDa membrane bound glycoprotein. Cancer Res. 1993; 53(16):3658-61. View

Barrand M, Rhodes T, CENTER M, Twentyman P . Chemosensitisation and drug accumulation effects of cyclosporin A, PSC-833 and verapamil in human MDR large cell lung cancer cells expressing a 190k membrane protein distinct from P-glycoprotein. Eur J Cancer. 1993; 29A(3):408-15. DOI: 10.1016/0959-8049(93)90397-x. View

Schneider E, Horton J, Yang C, Nakagawa M, Cowan K . Multidrug resistance-associated protein gene overexpression and reduced drug sensitivity of topoisomerase II in a human breast carcinoma MCF7 cell line selected for etoposide resistance. Cancer Res. 1994; 54(1):152-8. View

10.

Barrand M, Wright K, Rabbitts P, Twentyman P . A 190-kilodalton protein overexpressed in non-P-glycoprotein-containing multidrug-resistant cells and its relationship to the MRP gene. J Natl Cancer Inst. 1994; 86(2):110-7. DOI: 10.1093/jnci/86.2.110. View

11.

Grant C, Valdimarsson G, Hipfner D, Almquist K, Cole S, Deeley R . Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs. Cancer Res. 1994; 54(2):357-61. View

12.

Rhodes T, Barrand M, Twentyman P . Modification by brefeldin A, bafilomycin A1 and 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD) of cellular accumulation and intracellular distribution of anthracyclines in the non-P-glycoprotein-mediated multidrug-resistant cell line COR-L23/R. Br J Cancer. 1994; 70(1):60-6. PMC: 2033314. DOI: 10.1038/bjc.1994.250. View

13.

Abe T, Mori T, Kohno K, Seiki M, Hayakawa T, Welgus H . Expression of 72 kDa type IV collagenase and invasion activity of human glioma cells. Clin Exp Metastasis. 1994; 12(4):296-304. DOI: 10.1007/BF01753836. View

14.

Kohno K, Tanimura H, Sato S, Nakayama Y, Makino Y, Wada M . Cellular control of human multidrug resistance 1 (mdr-1) gene expression in absence and presence of gene amplification in human cancer cells. J Biol Chem. 1994; 269(32):20503-8. View

15.

Abe T, Hasegawa S, Taniguchi K, Yokomizo A, Kuwano T, Ono M . Possible involvement of multidrug-resistance-associated protein (MRP) gene expression in spontaneous drug resistance to vincristine, etoposide and adriamycin in human glioma cells. Int J Cancer. 1994; 58(6):860-4. DOI: 10.1002/ijc.2910580619. View

16.

Cole S, Sparks K, Fraser K, Loe D, Grant C, WILSON G . Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. Cancer Res. 1994; 54(22):5902-10. View

17.

Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y . Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res. 1981; 41(5):1967-72. View

18.

Cornwell M, Pastan I, Gottesman M . Certain calcium channel blockers bind specifically to multidrug-resistant human KB carcinoma membrane vesicles and inhibit drug binding to P-glycoprotein. J Biol Chem. 1987; 262(5):2166-70. View

19.

Mirski S, Gerlach J, Cole S . Multidrug resistance in a human small cell lung cancer cell line selected in adriamycin. Cancer Res. 1987; 47(10):2594-8. View

20.

Shiraishi N, Akiyama S, Nakagawa M, Kobayashi M, Kuwano M . Effect of bisbenzylisoquinoline (biscoclaurine) alkaloids on multidrug resistance in KB human cancer cells. Cancer Res. 1987; 47(9):2413-6. View