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Effects of Hydroxychloroquine Co-administered with Chemotherapeutic Agents on Malignant Glioma Cell Lines : in vitro Study  

Park, Yong-Sook (Department of Neurosurgery, Brain Korea21 Project for Medical Science, Yonsei University College of Medicine)
Choi, Jae-Young (Department of Neurosurgery, Brain Korea21 Project for Medical Science, Yonsei University College of Medicine)
Chang, Jong-Hee (Department of Neurosurgery, Brain Korea21 Project for Medical Science, Yonsei University College of Medicine)
Park, Yong-Gou (Department of Neurosurgery, Brain Korea21 Project for Medical Science, Yonsei University College of Medicine)
Chang, Jin-Woo (Department of Neurosurgery, Brain Korea21 Project for Medical Science, Yonsei University College of Medicine)
Publication Information
Journal of Korean Neurosurgical Society / v.38, no.1, 2005 , pp. 47-53 More about this Journal
Abstract
Objective : Anti-malaria drugs may modulate tumor resistance to chemotherapeutic agents, but it has not been proven effective in the treatment of malignant gliomas. The aim of this study was to determine whether adequate pre-clinical data on co-administration of chemotherapeutic agents with anti-malaria drugs on malignant cell lines could be obtained that would warrant its further potential consideration for use in a clinical trial for malignant gliomas. Methods : Two malignant glioma cell lines [U87MG, T98G] were treated with chemotherapeutic agents alone or with anti-malaria drugs. Cells were incubated with drugs for 4 days. Following the 4-day incubation, drug sensitivity assays were performed using 3-[4,5-dimethyl-2-thiazol-2-yl] 2,5-diphenyltetrazolium bromide [MTT] assay following optimization of experimental conditions for each cell lines and cell viability was calculated. Results : In all of four chemotherapeutic agents[doxorubicin. vincrisitne, nimustine, and cisplatin], the cell viability was found to be markedly decreased when hydroxychloroquine was co-administered on both U87MG and T98G cell lines. The two way analysis of variance[ANOVA] yielded a statistically significant two-sided p-value of 0.0033[doxorubicin], 0.0005[vincrisitne], 0.0007[nimustine], and 0.0003[cisplatin] on U87MG cell lines and 0.0006[doxorubicin], 0.0421[vincrisitne], 0.0317[nimustine], and 0.0001[cisplatin] on T98G cell lines, respectively. However, treatment with chloroquine and primaquine did not induce a decrease in cell viability on both U87MG and T98G cell lines. Conclusion : Our data support further consideration of the use of hydroxychloroquine prior to systemic chemotherapy to maximize its tumoricidal effect for patients with malignant gliomas.
Keywords
Anti-malarial drugs; Hydroxychloroquine; Chemotherapy; Multidrug resistance; Malignant glioma;
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1 Gros P, Croop J, Housman D : Mammalian multidrug resistance gene : complete cDNA sequence indicates strong homology to bacterial transport proteins. Cell 47 : 371-380, 1986   DOI   ScienceOn
2 Harrison DJ : Molecular mechanisms of drug resistance in tumors. J Pathol 175 : 7-12, 1995   DOI   PUBMED   ScienceOn
3 Kang MS, Kim HS, Han JA, Park SC, Kim WB, Park JG : Characteristics of human gastric carcinoma cell lines with induced multidrug resistance. Anticancer Res 17 : 3531-3536, 1997   PUBMED
4 Kohnoe S, Moriguchi S, Emi Y, Sakaguchi Y, Maehara Y, Ishida T, et al : Lung adenocarcinoma is more sensitive than gastric adenocarcinoma to anticancer drugs in vitro. Eur J Surg Oncol 17 : 47-50, 1991   PUBMED
5 Lum BL, Fisher GA, Brophy NA, Yahanda AM, Adler KM, Kaubisch S, et al : Clinical trials of modulation of multidrug resistance. Pharmacokinetic and pharmacodynamic considerations. Cancer 72 : 3502-3514, 1993   DOI   PUBMED   ScienceOn
6 Meerum Terwogt JM, Malingre MM, Beijnen JH, ten Bokkel Huinink WW, Rosing H, Koopman FJ, et al : Coadministration of oral cyclosporin A enables oral therapy with paclitaxel. Clin Cancer Res 5 : 3379-3384, 1999   PUBMED
7 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 41 : 1967-1972, 1981   PUBMED
8 Veneroni S, Zaffaroni N, Daidone MG, Benini E, Villa R, Silvestrini R : Expression of p-glycoprotein and in vitro or in vivo resistance to doxorubicin in and cisplatin in breast and ovarian cancers. Eur J Cancer 30A : 1002-1007, 1994   PUBMED
9 Wolf R, Wolf D, Ruocco V : Antimalarials : Unapproved uses or indication. Clin Dermatol 18 : 17-35, 2000   DOI   ScienceOn
10 Abad A, Massuti B, Blanco E, Carrato A, Maurel J, Cervantes A, et al : Seventy-two hour epirubicin infusion plus quinidine in unresectable and metastatic adenocarcinoma of the pancreas : a phase II trial. Am J Clin Oncol 21 : 151-154, 1998   DOI   ScienceOn
11 Kim JS, Amorino GP, Pyo H, Cao Q, Choy H : Radiation enhancement by the combined use of topoisomerase I inhibitors, RFS-2000 or CPT-11, and topoisomerase II inhibitor etoposide in human lung cancer cells. Radiother Oncol 62 : 61-67, 2002   DOI   ScienceOn
12 Ziemann C, Burkle A, Kahl GF, Hirsch-Ernst KI : Reactive oxygen species participate in mdr1b mRNA and P-glycoprotein overexpression in primary rat hepatocyte cultures. Carcinogenesis 20 : 407-414, 1999   DOI   ScienceOn
13 Raderer M, Scheithauer W : Clinical trials of agents that reverse multidrug resistance. A literature review. Cancer 72 : 3553-3563, 1993   DOI   PUBMED   ScienceOn
14 Beck WT, Grogan TM, Willman CL, Cordon-Cardo C, Parham DM, Kuttesch JF, et al : Methods to detect P-glycoprotein-associated multidrug resistance in patients' tumors : consensus recommendations. Cancer Res 56 : 3010-3020, 1996   PUBMED
15 Narasaki F, Matsuo I, Ikuno N, Fukuda M, Soda H, Oka M : Multidrug resistance-associated protein (MRP) gene expression in human lung cancer. Anticancer Res 16 : 2079-2082, 1996   PUBMED
16 Rhee HI, Kim JH, Kim CJ, Lee JK, Kwun BD : Does an Adjuvant Chemotherapy Really Help Patients with Glioblastoma? J Korean Neurosurg Soc 30 : 266-272, 2001
17 Pinedo HM, Giaccone G : P-Glycoprotein A Marker of Cancer-Cell Behavior. N Engl J Med 333 : 1417-1419, 1995   DOI   ScienceOn
18 Kirches E, Oda Y, Von Bossanyi P, Diete S, Schneider T, Warich- Kirches M, et al : Mdr1 mRNA expression differs between grade III astrocytomas and glioblastomas. Clin Neuropathol 16 : 34-36, 1997   PUBMED
19 Leyland-Jones B, Dalton W, Fisher GA, Sikic BI : Reversal of multidrug resistance to cancer chemotherapy. Cancer 72 : 3484-3488, 1993   DOI   PUBMED   ScienceOn
20 Biedler JL, Riehm H, Peterson RH, Spengler BA : Membrane-mediated drug resistance and phenotypic reversion to normal growth behavior of Chinese hamster cells. J Natl Cancer Inst 55 : 671-680, 1975   DOI   PUBMED
21 Bennis S, Ichas F, Robert J : Differential effects of verapamil and quinine on the reversal of doxorubicin resistance in a human leukemia cell line. Int J Cancer 62 : 283-290, 1995   DOI   ScienceOn
22 Scala S, Dickstein B, Regis J, Szallasi Z, Blumberg PM, Bates SE : Bryostatin 1 affects P-glycoprotein phosphorylation but not function in multidrug-resistant human breast cancer cells. Clin Cancer Res 1 : 1581-1587, 1995   PUBMED
23 Idriss HT, Hannun YA, Boulpaep E, Basavappa S : Regulation of volume-activated chloride channels by P-glycoprotein : phosphorylation has the final say! J Physiol 524 : 629-636, 2000   DOI   ScienceOn
24 Lagneaux L, Delforge A, Carlier S, Massy M, Bernier M, Bron D : Early induction of apoptosis in B-chronic lymphocytic leukaemia cells by hydroxychloroquine : activation of caspase-3 and no protection by survival factors. Bri J Haematol 112 : 344-352, 2001   DOI   ScienceOn
25 Hu YP, Chapey C, Robert J : Relationship between the inhibition of azidopine binding to P-glycoprotein by MDR modulators and their efficiency in restoring doxorubicin intracellular accumulation. Cancer Lett 109 : 203-209, 1996   DOI   PUBMED   ScienceOn
26 Inaba M, Maruyama E : Reversal of resistance to vincristine in P388 leukemia by various polycyclic clinical drugs, with a special emphasis on quinacrine. Cancer Res. 48 : 2064-2067, 1988   PUBMED
27 Ling V, Thompson LH : Reduced permeability in CHO cells as a mechanism of resistance to colchicine. J Cell Physiol 83 : 103-116, 1974   DOI   PUBMED
28 Dietzmann K, Bossanyi P, Franke DS : Expression of P-glycoprotein as a multiple resistance gene product in human protoplasmatic astrocytes and astrocytoma. Zentralbl Pathol 140 : 149-153, 1994   PUBMED
29 Spoelstra EC, Dekker H, Schuurhuis GJ, Broxterman HJ, Lankelma J : P-glycoprotein drug efflux pump involved in the mechanisms of intrinsic drug resistance in various colon cancer cell lines. Evidence for a saturation of active daunorubicin transport. Biochem Pharmacol 41 : 349-359, 1991   DOI   ScienceOn
30 Allalunis-Turner MJ, Barron GM, Day RS III, Dobler K, Urtasun RC : Heterogeneity in response to treatment with buthionine sulfoximine or interferon in human malignant glioma cells. Int J Radiat Oncol Biol Phys 22 : 765-768, 1992   DOI   PUBMED   ScienceOn
31 Ichikawa M, Yoshimura A, Furukawa T, Sumizawa T, Nakazima Y, Akiyama S : Glycosylation of P-glycoprotein in a multidrug-resistant KB cell line, and in the human tissues. Biochim Biophys Acta 1073 : 309-315, 1991   DOI   PUBMED   ScienceOn
32 Fojo AT, Shen DW, Mickley LA, Pastan I, Gottesman MM : Intrinsic drug resistance in human kidney cancer is associated with expression of a human multidrug-resistance gene. J Clin Oncol 5 : 1922-1927, 1987   DOI   PUBMED