Mefloquine induces cell death in prostate cancer cells and provides a potential novel treatment strategy in vivo

Yan,Kun‑Huang; Lin,Yung‑Wei; Hsiao,Chi‑Hao; Wen,Yu‑Ching; Lin,Ke‑Hsun; Liu,Chung‑Chi; Hsieh,Mao‑Chih; Yao,Chih‑Jung; Yan,Ming‑De; Lai,Gi‑Ming; Chuang,Shuang‑En; Lee,Liang‑Ming

doi:10.3892/ol.2013.1259

May 2013 Volume 5 Issue 5

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May 2013 Volume 5 Issue 5

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Article

Mefloquine induces cell death in prostate cancer cells and provides a potential novel treatment strategy in vivo

Authors:
- Kun‑Huang Yan
- Yung‑Wei Lin
- Chi‑Hao Hsiao
- Yu‑Ching Wen
- Ke‑Hsun Lin
- Chung‑Chi Liu
- Mao‑Chih Hsieh
- Chih‑Jung Yao
- Ming‑De Yan
- Gi‑Ming Lai
- Shuang‑En Chuang
- Liang‑Ming Lee
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Affiliations: Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, R.O.C., Division of General Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, R.O.C. , Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, R.O.C., Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, R.O.C., National Institutes of Cancer Research, National Health Research Institutes, Miaoli, Taiwan, R.O.C.
Pages: 1567-1571
|
Published online on: March 15, 2013

https://doi.org/10.3892/ol.2013.1259
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Abstract

Mefloquine (MQ) is currently in clinical use as a prophylactic treatment for malaria. Previous studies have shown that MQ induces oxidative stress in vitro. The present study investigated the anticancer effects of MQ treatment in PC3 cells. The cell viability was evaluated using sulphorhodamine-B (SRB) staining, while annexin V and propidium iodide (PI) were used as an assay for cell death. Reactive oxygen species (ROS) formation was detected with 2',7'‑dichlorofluorescein‑diacetate (DCFH‑DA), a sensitive intracellular probe, and the alteration of cellular status was defined by trypan blue staining. The results of the present study indicated that MQ has a high cytotoxicity that causes cell death in PC3 cells. MQ markedly inhibited the PC3 cells through non‑apoptotic cell death. MQ also induced significant ROS production. The MQ treatment mediated G1 cell cycle arrest and cyclin D1 accumulation through p21 upregulation in the PC3 cells. Moreover, the use of MQ improved the survival of the treatment group compared with the control group in the experimental mice. The present study indicates that MQ possesses potential therapeutic efficacy for the treatment of prostate cancer (PCa) in vivo. These findings provide insights that may aid the further optimization and application of new and existing therapeutic options.

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1	Sotelo J, Briceño E and López-González MA: Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 144:337–343. 2006. View Article : Google Scholar : PubMed/NCBI
2	Briceño E, Reyes S and Sotelo J: Therapy of glioblastoma multiforme improved by the antimutagenic chloroquine. Neurosurg Focus. 14:e32003.PubMed/NCBI
3	Geng Y, Kohli L, Klocke BJ and Roth KA: Chloroquine-induced autophagic vacuole accumulation and cell death in glioma cells is p53 independent. Neuro Oncol. 12:473–481. 2010.PubMed/NCBI
4	Sharma N, Thomas S, Golden EB, Hofman FM, Chen TC, Petasis NA, Schönthal AH and Louie SG: Inhibition of autophagy and induction of breast cancer cell death by mefloquine, an anti-malarial agent. Cancer Lett. 326:143–154. 2012. View Article : Google Scholar : PubMed/NCBI
5	Taylor WR and White NJ: Antimalarial drug toxicity: a review. Drug Saf. 27:25–61. 2004. View Article : Google Scholar : PubMed/NCBI
6	ter Kuile FO, Nosten F, Thieren M, Luxemburger C, Edstein MD, Chongsuphajaisiddhi T, Phaipun L, Webster HK and White NJ: High-dose mefloquine in the treatment of multidrug-resistant falciparum malaria. J Infect Dis. 166:1393–1400. 1992.
7	Krudsood S, Looareesuwan S, Wilairatama P, Leowattana W, Tangpukdee N, Chalermrut K, Ramanathan S, Navaratnam V, Olliaro P, Vaillant M, Kiechel JR and Taylor WR: Effect of artesunate and mefloquine in combination on the Fridericia corrected QT intervals in Plasmodium falciparum infected adults from Thailand. Trop Med Int Health. 16:458–465. 2011. View Article : Google Scholar : PubMed/NCBI
8	Dow GS, Caridha D, Goldberg M, Wolf L, Koenig ML, Yourick DL and Wang Z: Transcriptional profiling of mefloquine-induced disruption of calcium homeostasis in neurons in vitro. Genomics. 86:539–550. 2005. View Article : Google Scholar : PubMed/NCBI
9	Simpson JA, Price R, ter Kuile F, Teja-Isavatharm P, Nosten F, Chongsuphajaisiddhi T, Looareesuwan S, Aarons L and White NJ: Population pharmacokinetics of mefloquine in patients with acute falciparum malaria. Clin Pharmacol Ther. 66:472–484. 1999. View Article : Google Scholar : PubMed/NCBI
10	Kollaritsch H, Karbwang J, Wiedermann G, Mikolasek A, Na-Bangchang K and Wernsdorfer WH: Mefloquine concentration profiles during prophylactic dose regimens. Wien Klin Wochenschr. 112:441–447. 2000.PubMed/NCBI
11	Bajgelman MC and Strauss BE: The DU145 human prostate carcinoma cell line harbors a temperature-sensitive allele of p53. Prostate. 66:1455–1462. 2006. View Article : Google Scholar : PubMed/NCBI
12	Isaacs WB, Carter BS and Ewing CM: Wild-type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles. Cancer Res. 51:4716–4720. 1991.PubMed/NCBI
13	Keepers YP, Pizao PE, Peters GJ, van Ark-Otte J, Winograd B and Pinedo HM: Comparison of the sulforhodamine B protein and tetrazolium (MTT) assays for in vitro chemosensitivity testing. Eur J Cancer. 27:897–900. 1991. View Article : Google Scholar : PubMed/NCBI
14	Abbas T and Dutta A: p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer. 9:400–414. 2009. View Article : Google Scholar : PubMed/NCBI
15	Hood JE, Jenkins JW, Milatovic D, Rongzhu L and Aschner M: Mefloquine induces oxidative stress and neurodegeneration in primary rat cortical neurons. Neurotoxicology. 31:518–523. 2010. View Article : Google Scholar : PubMed/NCBI
16	Di Stefano A, Frosali S, Leonini A, Ettorre A, Priora R, Di Simplicio FC and Di Simplicio P: GSH depletion, protein S-glutathionylation and mitochondrial transmembrane potential hyperpolarization are early events in initiation of cell death induced by a mixture of isothiazolinones in HL60 cells. Biochim Biophys Acta. 1763:214–225. 2006.PubMed/NCBI
17	Skulachev VP: Bioenergetic aspects of apoptosis, necrosis and mitoptosis. Apoptosis. 11:473–485. 2006. View Article : Google Scholar : PubMed/NCBI
18	Choi K, Kim J, Kim GW and Choi C: Oxidative stress-induced necrotic cell death via mitochondria-dependent burst of reactive oxygen species. Curr Neurovasc Res. 6:213–222. 2009. View Article : Google Scholar : PubMed/NCBI