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Calcium and oxidative stress mediate perillaldehyde-induced apoptosis in Candida albicans

  • Applied microbial and cell physiology
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

An Erratum to this article was published on 22 March 2017

Abstract

New anti-Candida albicans drugs are needed due to the emergence of resistant cases in recent years. Perillaldehyde (PAE) is a natural monoterpenoid compound derived from Perilla frutescens. The minimum inhibitory concentration of PAE against C. albicans was 0.4 μL/mL. We aimed to elucidate the antifungal mode of action of PAE against C. albicans. The antifungal activity of PAE against C. albicans was found to correlate with an elevation in intracellular Ca2+ and accumulation of ROS. Several downstream apoptosis events such as the disruption of mitochondrial membrane potential, phosphatidylserine externalization, cytochrome c release, and metacaspase activation were observed in PAE-treated cells. DNA damage and nuclear fragmentation assays also revealed apoptosis of C. albicans cells. In summary, by means of fluorescent microscopy, flow cytometer analysis, and Western blot, our data uncovered that PAE exerts its antifungal activity through Ca2+ and oxidative stress-mediated apoptosis mechanisms. This study deciphered the mode of action of PAE, which will be useful in the design of improved antifungal therapies.

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References

  • Amin S, Mousavi A, Robson GD (2004) Oxidative and amphotericin B-mediated cell death in the opportunistic pathogen Aspergillus fumigatus is associated with an apoptotic-like phenotype. Microbiology-Sgm 150(6):1937–1945

    Article  CAS  Google Scholar 

  • Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, Linder T, Wawrosch C, Uhrin P, Temml V, Wang LM, Schwaiger S, Heiss EH, Rollinger JM, Schuster D, Breuss JM, Bochkov V, Mihovilovic MD, Kopp B, Bauer R, Dirsch VM, Stuppner H (2015) Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv 33(8):1582–1614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barroso G, Taylor S, Morshedi M, Manzur F, Gavino F, Oehninger S (2006) Mitochondrial membrane potential integrity and plasma membrane translocation of phosphatidylserine as early apoptotic markers: a comparison of two different sperm subpopulations. Fertil Steril 85(1):149–154

    Article  CAS  PubMed  Google Scholar 

  • Benaroudj N, Lee DH, Goldberg AL (2001) Trehalose accumulation during cellular stress protects cells and cellular proteins from damage by oxygen radicals. J Biol Chem 276(26):24261–24267

    Article  CAS  PubMed  Google Scholar 

  • Buttner S, Eisenberg T, Carmona-Gutierrez D, Ruli D, Knauer H, Ruckenstuhl C, Sigrist C, Wissing S, Kollroser M, Frohlich KU, Sigrist S, Madeo F (2007) Endonuclease G regulates budding yeast life and death. Mol Cell 25(2):233–246

    Article  PubMed  Google Scholar 

  • Cao YY, Huang S, Dai BD, Zhu ZY, Lu H, Dong LL, Cao YB, Wang Y, Gao PH, Chai YF, Jiang YY (2009) Candida albicans cells lacking CaMCA1-encoded metacaspase show resistance to oxidative stress-induced death and change in energy metabolism. Fungal Genet Biol 46(2):183–189

    Article  CAS  PubMed  Google Scholar 

  • Chen WJ, Yu C, Yang Z, He JL, Yin J, Liu HZ, Liu HT, Wang YX (2012) Tubeimoside-1 induces G2/M phase arrest and apoptosis in SKOV-3 cells through increase of intracellular Ca2+ and caspase-dependent signaling pathways. Int J Oncol 40(2):535–543

    PubMed  Google Scholar 

  • Cheng JJ, Park TS, Chio LC, Fischl AS, Ye XS (2003) Induction of apoptosis by sphingoid long-chain bases in Aspergillus nidulans. Mol Cell Biol 23(1):163–177

  • Cheng XL, Zhang WQ, Ji YL, Meng J, Guo H, Liu J, Wu XC, Xu HY (2013) Revealing silver cytotoxicity using Au nanorods/Ag shell nanostructures: disrupting cell membrane and causing apoptosis through oxidative damage. RSC Adv 3(7):2296–2305

    Article  CAS  Google Scholar 

  • Cho J, Lee DG (2011) The antimicrobial peptide arenicin-1 promotes generation of reactive oxygen species and induction of apoptosis. Biochim Biophys Acta 1810(12):1246–1251

    Article  CAS  PubMed  Google Scholar 

  • Collins JA, Schandl CA, Young KK, Vesely J, Willingham MC (1997) Major DNA fragmentation is a late event in apoptosis. J Histochem Cytochem 45(7):923–934

    Article  CAS  PubMed  Google Scholar 

  • Daniel B, DeCoster MA (2004) Quantification of sPLA(2)-induced early and late apoptosis changes in neuronal cell cultures using combined TUNEL and DAPI staining. Brain Res Protocol 13(3):144–150

    Article  CAS  Google Scholar 

  • Dobrucki J, Darzynkiewicz Z (2001) Chromatin condensation and sensitivity of DNA in situ to denaturation during cell cycle and apoptosis—a confocal microscopy study. Micron 32(7):645–652

    Article  CAS  PubMed  Google Scholar 

  • Frey TG, Mannella CA (2000) The internal structure of mitochondria. Trends Biochem Sci 25(7):319–324

    Article  CAS  PubMed  Google Scholar 

  • Gavrieli Y, Sherman Y, Ben-Sasson SA (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Biol 119(3):493–501

    CAS  Google Scholar 

  • Gogvadze V, Orrenius S (2006) Mitochondrial regulation of apoptotic cell death. Chem Biol Interact 163(1–2):4–14

    Article  CAS  PubMed  Google Scholar 

  • Hwang JH, Hwang IS, Liu QH, Woo ER, Lee DG (2012) (+)-Medioresinol leads to intracellular ROS accumulation and mitochondria-mediated apoptotic cell death in Candida albicans. Biochimie 94(8):1784–1793

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi D, Kondo K, Uehara N, Otokozawa S, Tsuji N, Yagihashi A, Watanabe N (2002) Endogenous reactive oxygen species is an important mediator of miconazole antifungal effect. Antimicrob Agents Chemother 46(10):3113–3117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kruman I, Guo Q, Mattson MP (1998) Calcium and reactive oxygen species mediate staurosporine-induced mitochondrial dysfunction and apoptosis in PC12 cells. J Neurosci Res 51(3):293–308

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Hwang JS, Hwang IS, Cho J, Lee E, Kim Y, Lee DG (2012) Coprisin-induced antifungal effects in Candida albicans correlate with apoptotic mechanisms. Free Radic Biol Med 52(11–12):2302–2311

    Article  CAS  PubMed  Google Scholar 

  • Lu Y, Su C, Liu HP (2014) Candida albicans hyphal initiation and elongation. Trends Microbiol 22(12):707–714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Machida K, Tanaka T, Fujita KI, Taniguchi M (1998) Farnesol-induced generation of reactive oxygen species via indirect inhibition of the mitochondrial electron transport chain in the yeast Saccharomyces cerevisiae. J Bacteriol 180(17):4460–4465

    CAS  PubMed  PubMed Central  Google Scholar 

  • Madeo F, Frohlich E, Frohlich KU (1997) A yeast mutant showing diagnostic markers of early and late apoptosis. J Cell Biol 139(3):729–734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Madeo F, Herker E, Maldener C, Wissing S, Lachelt S, Herlan M, Fehr M, Lauber K, Sigrist SJ, Wesselborg S, Frohlich KU (2002) A caspase-related protease regulates apoptosis in yeast. Mol Cell 9(4):911–917

    Article  CAS  PubMed  Google Scholar 

  • Mallick S, Dey S, Mandal S, Dutta A, Mukherjee D, Biswas G, Chatterjee S, Mallick S, Lai TK, Acharya K, Pal C (2015) A novel triterpene from Astraeus hygrometricus induces reactive oxygen species leading to death in Leishmania donovani. Future Microbiol 10(5):763–789

    Article  CAS  PubMed  Google Scholar 

  • Maurya IK, Thota CK, Sharma J, Tupe SG, Chaudhary P, Singh MK, Thakur IS, Deshpande M, Prasad R, Chauhan VS (2013) Mechanism of action of novel synthetic dodecapeptides against Candida albicans. Biochim Biophys Acta 1830(11):5193–5203

    Article  CAS  PubMed  Google Scholar 

  • Munoz AJ, Wanichthanarak K, Meza E, Petranovic D (2012) Systems biology of yeast cell death. FEMS Yeast Res 12(2):249–265

    Article  CAS  PubMed  Google Scholar 

  • Pinto E, Hrimpeng K, Lopes G, Vaz S, Goncalves MJ, Cavaleiro C, Salgueiro L (2013) Antifungal activity of Ferulago capillaris essential oil against Candida, Cryptococcus, Aspergillus and dermatophyte species. Eur J Clin Microbiol Infect Dis 32(10):1311–1320

    Article  CAS  PubMed  Google Scholar 

  • Pushpanathan M, Gunasekaran P, Rajendhran J (2013) Mechanisms of the antifungal action of marine metagenome-derived peptide, MMGP1, against Candida albicans. PLoS ONE 8(7)

  • Sen Gupta S, Ton VK, Beaudry V, Rulli S, Cunningham K, Rao R (2003) Antifungal activity of amiodarone is mediated by disruption of calcium homeostasis. J Biol Chem 278(31):28831–28839

    Article  Google Scholar 

  • Sharon A, Finkelstein A, Shlezinger N, Hatam I (2009) Fungal apoptosis: function, genes and gene function. FEMS Microbiol Rev 33(5):833–854

    Article  CAS  PubMed  Google Scholar 

  • Tian J, Ban XQ, Zeng H, He JS, Chen YX, Wang YW (2012) The mechanism of antifungal action of essential oil from dill (Anethum graveolens L.) on Aspergillus flavus. PLoS ONE 7(1)

  • Tian J, Zeng XB, Zhang S, Wang YZ, Zhang P, Lu AJ, Peng X (2014) Regional variation in components and antioxidant and antifungal activities of Perilla frutescens essential oils in China. Ind Crop and Prod 59:69–79

    Article  CAS  Google Scholar 

  • Tian J, Wang YZ, Zeng H, Li ZY, Zhang P, Tessema A, Peng X (2015a) Efficacy and possible mechanisms of perillaldehyde in control of Aspergillus niger causing grape decay. Int J Food Microbiol 202(2):27–34

    Article  CAS  PubMed  Google Scholar 

  • Tian J, Zeng XB, Lu AJ, Zhu AH, Peng X, Wang YW (2015b) Perillaldehyde, a potential preservative agent in foods: assessment of antifungal activity against microbial spoilage of cherry tomatoes. Lwt-Food Sci Technol 60(1):63–70

    Article  CAS  Google Scholar 

  • Tian J, Wang YZ, Lu ZQ, Sun CH, Zhang M, Zhu AH, Peng X (2016) Perillaldehyde, a promising antifungal agent used in food preservation, triggers apoptosis through a metacaspase-dependent pathway in Aspergillus flavus. J Agric Food Chem 64(39):7404–7413

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Youle RJ (2009) The role of mitochondria in apoptosis. Annu Rev Genet 43:95–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu XZ, Chang WQ, Cheng AX, Sun LM, Lou HX (2010) Plagiochin E, an antifungal active macrocyclic bis(bibenzyl), induced apoptosis in Candida albicans through a metacaspase-dependent apoptotic pathway. Biochim Biophys Acta 1800(4):439–447

    Article  CAS  PubMed  Google Scholar 

  • Yun DG, Lee DG (2016) Silibinin triggers yeast apoptosis related to mitochondrial Ca2+ influx in Candida albicans. Int J Biochem Cell Biol 80:1–9

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was funded by National Natural Science Foundation of China (31671944, 31301585), Qing Lan Project of Jiangsu Province, National Undergraduate Training Programs for Innovation and Entrepreneurship (201610320027), Xinjiang Production & Construction Crops, Key Laboratory of Protection and Utilization of Biological Resources in Tarim Basin (BRZD1502), China Postdoctoral Science Foundation (2016M600678), the Industry-University-Academy Prospective Joint Research Project of Jiangsu Province (BY2016028-01), and the PAPD of Jiangsu Higher Education Institutions.

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Authors and Affiliations

  1. College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People’s Republic of China

    Hui Tian, Su Qu, Yanzhen Wang, Zhaoqun Lu, Man Zhang, Yeyun Gan, Peng Zhang & Jun Tian

  2. Key Lab for New Drug Research of TCM and Shenzhen Branch, State R&D Centre for Viro-Biotech, Research Institute of Tsinghua University in Shenzhen, Shenzhen, Guangdong, People’s Republic of China

    Jun Tian

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  1. Hui Tian
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Correspondence to Peng Zhang or Jun Tian.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Hui Tian and Su Qu contributed equally to this work

An erratum to this article is available at http://dx.doi.org/10.1007/s00253-017-8217-5.

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Tian, H., Qu, S., Wang, Y. et al. Calcium and oxidative stress mediate perillaldehyde-induced apoptosis in Candida albicans . Appl Microbiol Biotechnol 101, 3335–3345 (2017). https://doi.org/10.1007/s00253-017-8146-3

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