Dehydrozingerone Exhibits Synergistic Antifungal Activities in Combination with Dodecanol against Budding Yeast via the Restriction of Multidrug Resistance

Chika Yamawaki; Yoshihiro Yamaguchi; Akira Ogita; Toshio Tanaka; Ken-ichi Fujita

doi:10.1055/a-0757-7991

Planta Medica International Open, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Planta Medica International Open 2018; 5(02): e61-e67
DOI: 10.1055/a-0757-7991

Original Papers

Dehydrozingerone Exhibits Synergistic Antifungal Activities in Combination with Dodecanol against Budding Yeast via the Restriction of Multidrug Resistance

Chika Yamawaki

¹Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka, Japan

,

Yoshihiro Yamaguchi

¹Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka, Japan

²Advanced Research Institute for Natural Science and Technology, Osaka City University, Sumiyoshi-ku, Osaka, Japan

,

Akira Ogita

¹Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka, Japan

³Research Center for Urban Health and Sports, Osaka City University, Sumiyoshi-ku, Osaka, Japan

,

Toshio Tanaka

¹Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka, Japan

,

Ken-ichi Fujita

¹Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka, Japan

› Institutsangaben

Abstract

Drug resistance in fungal infections has been a more frequent occurrence with the increasing number of immunocompromised patients. In efforts to overcome the problem of fungal drug resistance, we focused on the phenolic compound dehydrozingerone, which is isolated from Zingiber officinale. The effectiveness of this compound on the model yeast Saccharomyces cerevisiae has not been reported. In our study, dehydrozingerone showed a weak antifungal activity against the yeast, but demonstrated a synergistic effect in combination with dodecanol, which typically only restricts cell growth transiently. Efflux of rhodamine 6G through the multidrug efflux pumps was significantly restricted by dehydrozingerone. The transcription level of PDR5, encoding a primary multidrug efflux pump in S. cerevisiae, was enhanced with dodecanol treatment, whereas the level was reduced by dehydrozingerone. These results suggest that dehydrozingerone may be effective for potentiating antifungal activity of other drugs that are expelled from fungi by multidrug transporters like Pdr5p.

Key words

ABC transporter - antifungal - dehydrozingerone - feruloylmethane - multidrug resistance - PDR5 - Saccharomyces cerevisiae - vanillylidenacetone

Volltext

Referenzen

References
1 Miceli MH, Díaz JA, Lee SA. Emerging opportunistic yeast infections. Lancet Infect Dis 2011; 11: 142-151
2 Fairlamb AH, Gow NA, Matthews KR, Waters AP. Drug resistance in eukaryotic microorganisms. Nature Microbiol 2016; 1: 16092
3 Masiá Canuto M, Gutiérrez Rodero F. Antifungal drug resistance to azoles and polyenes. Lancet Infect Dis 2002; 2: 550-563
4 Polak A, Hartman PG. Antifungal chemotherapy–are we winning?. Prog Drug Res 1991; 37: 181-269
5 Gonçalves SS, Souza ACR, Chowdhary A, Meis JF, Colombo AL. Epidemiology and molecular mechanisms of antifungal resistance in Candida and Aspergillus . Mycoses 2016; 59: 198-219
6 Ghannoum MA, Rice LB. Antifungal agents: Mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin Microbiol Rev 1999; 12: 501-517
7 Li XZ, Nikaido H. Efflux-mediated drug resistance in bacteria: An update. Drugs 2009; 69: 1555-1623
8 Cannon RD, Lamping E, Holmes AR, Niimi K, Baret PV, Keniya MV, Tanabe K, Niimi M, Goffeau A, Monk BC. Efflux-mediated antifungal drug resistance. Clin Microbiol Rev 2009; 22: 291-321
9 Paul S, Moye-Rowley WS. Multidrug resistance in fungi: Regulation of transporter-encoding gene expression. Front Physiol 2014; 5: 143
10 Lu WD, Qin Y, Yang C, Li L, Fu ZX. Effect of curcumin on human colon cancer multidrug resistance in vitro and in vivo. Clinics (Sao Paulo) 2013; 68: 694-701
11 Tang XQ, Bi H, Feng JQ, Cao JG. Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR. Acta Pharmacol Sin 2005; 26: 1009-1016
12 Si M, Zhao J, Li X, Tian JG, Li YG, Li JM. Reversion effects of curcumin on multidrug resistance of MNNG/HOS human osteosarcoma cells in vitro and in vivo through regulation of P-glycoprotein. Chin Med J 2013; 126: 4116-4123
13 Sharma M, Manoharlal R, Shukla S, Puri N, Prasad T, Ambudkar SV, Prasad R. Curcumin modulates efflux mediated by yeast ABC multidrug transporters and is synergistic with antifungals. Antimicrob Agents Chemother 2009; 53: 3256-3265
14 Tatsuzaki J, Bastow KF, Nakagawa-Goto K, Nakamura S, Itokawa H, Lee KH. Dehydrozingerone, chalcone, and isoeugenol analogues as in vitro anticancer agents. J Nat Prod 2006; 69: 1445-1449
15 Fujita K, Ishikura T, Jono Y, Yamaguchi Y, Ogita A, Kubo I, Tanaka T. Anethole potentiates dodecanol's fungicidal activity by reducing PDR5 expression in budding yeast. Biochim Biophys Acta 2017; 1861: 477-484
16 Hampannavar GA, Karpoormath R, Palkar MB, Shaikh MS. An appraisal on recent medicinal perspective of curcumin degradant: Dehydrozingerone (DZG). Bioorg Med Chem 2016; 24: 501-520
17 Kubra IR, Murthy PS, Rao LJ. In vitro antifungal activity of dehydrozingerone and its fungitoxic properties. J Food Sci 2013; 78: M64-M69
18 Salin H, Fardeau V, Piccini E, Lelandais G, Tanty V, Lemoine S, Jacq C, Devaux F. Structure and properties of transcriptional networks driving selenite stress response in yeasts. BMC Genomics 2008; 9: 333
19 Sipos G, Kuchler K. Fungal ATP-binding cassette (ABC) transporters in drug resistance & detoxification. Curr Drug Targets 2006; 7: 471-481
20 Ma M, Liu ZL. Comparative transcriptome profiling analyses during the lag phase uncover YAP1, PDR1, PDR3, RPN4, and HSF1 as key regulatory genes in genomic adaptation to the lignocellulose derived inhibitor HMF for Saccharomyces cerevisiae . BMC Genomics 2010; 11: 660
21 Fujita K, Tatsumi M, Ogita A, Kubo I, Tanaka T. Anethole induces apoptotic cell death accompanied by reactive oxygen species production and DNA fragmentation in Aspergillus fumigatus and Saccharomyces cerevisiae . FEBS J 2014; 281: 1304-1313
22 Yogosawa S, Yamada Y, Yasuda S, Sun Q, Takizawa K, Sakai T. Dehydrozingerone, a structural analogue of curcumin, induces cell-cycle arrest at the G2/M phase and accumulates intracellular ROS in HT-29 human colon cancer cells. J Nat Prod 2012; 75: 2088-2093
23 Cuenca-Estrella M, Gomez-Lopez A, Mellado E, Monzon A, Buitrago MJ, Rodriguez-Tudela JL. Activity profile in vitro of micafungin against Spanish clinical isolates of common and emerging species of yeasts and molds. Antimicrob Agents Chemother 2009; 53: 2192-2195
24 Yutani M, Hashimoto Y, Ogita A, Kubo I, Tanaka T, Fujita K. Morphological changes of the filamentous fungus Mucor mucedo and inhibition of chitin synthase activity induced by anethole. Phytother Res 2011; 25: 1707-1713
25 Fujita K, Fujita T, Kubo I. Anethole, a potential antimicrobial synergist, converts a fungistatic dodecanol to a fungicidal agent. Phytother Res 2007; 21: 47-51
26 Anuchapreeda S, Leechanachai P, Smith MM, Ambudkar SV, Limtrakul PN. Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells. Biochem Pharmacol 2002; 64: 573-582
27 Choi BH, Kim CG, Lim Y, Shin SY, Lee YH. Curcumin down-regulates the multidrug-resistance mdr1b gene by inhibiting the PI3K/Akt/NFκB pathway. Cancer Lett 2008; 259: 111-118
28 Fujita K, Kubo I. Antifungal activity of octyl gallate. Int J Food Microbiol 2002; 79: 193-201
29 Kubo I, Fujita K, Kubo A, Nihei K, Lunde CS. Modes of antifungal action of (2E)-alkenals against Saccharomyces cerevisiae . J Agric Food Chem 2003; 51: 3951-3957
30 Niimi M, Niimi K, Takano Y, Holmes AR, Fischer FJ, Uehara Y, Cannon RD. Regulated overexpression of CDR1 in Candida albicans confers multidrug resistance. J Antimicrob Chemother 2004; 54: 999-1006