Open Access

Potential use of Pichia pastoris strain SMD1168H expressing DNA topoisomerase I in the screening of potential anti‑breast cancer agents

  • Authors:
    • Jian Xin
    • Wan Nor Azlin Wan Mahtar
    • Poh Chiew Siah
    • Noorizan Miswan
    • Boon Yin Khoo
  • View Affiliations

  • Published online on: April 30, 2019     https://doi.org/10.3892/mmr.2019.10201
  • Pages: 5368-5376
  • Copyright: © Xin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Cancer chemotherapy possesses high toxicity, particularly when a higher concentration of drugs is administered to patients. Therefore, searching for more effective compounds to reduce the toxicity of treatments, while still producing similar effects as current chemotherapy regimens, is required. Currently, the search for potential anticancer agents involves a random, inaccurate process with strategic deficits and a lack of specific targets. For this reason, the initial in vitro high‑throughput steps in the screening process should be reviewed for rapid identification of the compounds that may serve as anticancer agents. The present study aimed to investigate the potential use of the Pichia pastoris strain SMD1168H expressing DNA topoisomerase I (SMD1168H‑TOPOI) in a yeast‑based assay for screening potential anticancer agents. The cell density that indicated the growth of the recombinant yeast without treatment was first measured by spectrophotometry. Subsequently, the effects of glutamate (agonist) and camptothecin (antagonist) on the recombinant yeast cell density were investigated using the same approach, and finally, the effect of camptothecin on various cell lines was determined and compared with its effect on recombinant yeast. The current study demonstrated that growth was enhanced in SMD1168H‑TOPOI as compared with that in SMD1168H. Glutamate also enhanced the growth of the SMD1168H; however, the growth effect was not enhanced in SMD1168H‑TOPOI treated with glutamate. By contrast, camptothecin caused only lower cell density and growth throughout the treatment of SMD1168H‑TOPOI. The findings of the current study indicated that SMD1168H‑TOPOI has similar characteristics to MDA‑MB‑231 cells; therefore, it can be used in a yeast‑based assay to screen for more effective compounds that may inhibit the growth of highly metastatic breast cancer cells.

References

1 

Brearley MJ: Chemotherapy. Feline Soft Tissue and General Surgery. Langley-Hobbs SJ, Demetriou JL and Ladlow JF: Elsevier Ltd.; Amsterdam: pp. 161–167. 2014, View Article : Google Scholar

2 

Lukong KE: Understanding breast cancer-The long and winding road. BBA Clin. 7:64–77. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Cimino GD, Pan CX and Henderson PT: Personalized medicine for targeted and platinum-based chemotherapy of lung and bladder cancer. Bioanalysis. 5:369–391. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Suzuki H, Asakawa A, Amitani H, Nakamura N and Inui A: Cancer cachexia-pathophysiology and management. J Gastroenterol. 48:574–594. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Ferioli M, Zauli G, Martelli AM, Vitale M, McCubrey JA, Ultimo S, Capitani S and Neri LM: Impact of physical exercise in cancer survivors during and after antineoplastic treatments. Oncotarget. 9:14005–14034. 2018. View Article : Google Scholar : PubMed/NCBI

6 

Wilkes GM: Targeted therapy: Attacking cancer with molecular and immunological targeted agents. Asia Pac J Oncol Nurs. 5:137–155. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Cragg GM, Boyd MR, Grever MR and Schepartz SA: Pharmaceutical prospecting and the potential for pharmaceutical crops. Natural product drug discovery and development at the United States National Cancer Institute. Ann Missouri Bot Gard. 82:47–53. 1995. View Article : Google Scholar

8 

Hermiston TW and Kirn DH: Genetically based therapeutics for cancer: Similarities and contrasts with traditional drug discovery and development. Mol Ther. 11:496–507. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Hughes JP, Rees S, Kalindjian SB and Philpott KL: Principles of early drug discovery. Br J Pharmacol. 162:1239–1249. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Katiyar C, Gupta A, Kanjilal S and Katiyar S: Drug discovery from plant sources: An integrated approach. Ayu. 33:10–19. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Pan SY, Zhou SF, Gao SH, Yu ZL, Zhang SF, Tang MK, Sun JN, Ma DL, Han YF, Fong WF and Ko KM: New perspectives on how to discover drugs from herbal medicines: CAM's outstanding contribution to modern therapeutics. Evid Based Complement Alternat Med. 2013:6273752013. View Article : Google Scholar : PubMed/NCBI

12 

Pharmaceutical Research and Manufacturers of America: Pharmaceutical Industry Profile 2010. PhRMA; Washington, DC: March. 2010

13 

Chan MK, Lim SK, Miswan N, Chew AL, Noordin R and Khoo BY: Expression of stable and active human DNA topoisomerase I in Pichia pastoris. Protein Expr Purif. 141:52–62. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Zaks-Makhina E, Kim Y, Aizenman E and Levitan ES: Novel neuroprotective K+ channel inhibitor identified by high-throughput screening in yeast. Mol Pharmacol. 65:214–219. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Wu B, Altmann K, Barzel I, Krehan S and Beitz E: A yeast-based phenotypic screen for aquaporin inhibitors. Pflugers Arch. 456:717–720. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Demirbas D, Ceyhan O, Wyman AR and Hoffman CS: A fission yeast-based platform for phosphodiesterase inhibitor HTSs and analyses of phosphodiesterase activity. Handb Exp Pharmacol. 135–149. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Ceyhan O, Birsoy K and Hoffman CS: Identification of biologically active PDE11-selective inhibitors using a yeast-based high-throughput screen. Chem Biol. 19:155–163. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Frame IJ, Deniskin R, Rinderspacher A, Katz F, Deng SX, Moir RD, Adjalley SH, Coburn-Flynn O, Fidock DA, Willis IM, et al: Yeast-based high-throughput screen identifies Plasmodium falciparum equilibrative nucleoside transporter 1 inhibitors that kill malaria parasites. ACS Chem Biol. 10:775–783. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Asai A, Tsujita T, Sharma SV, Yamashita Y, Akinaga S, Funakoshi M, Kobayashi H and Mizukami T: A new structural class of proteasome inhibitors identified by microbial screening using yeast-based assay. Biochem Pharmacol. 67:227–234. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Ang RP, Teoh LS, Chan MK, Miswan N and Khoo BY: Comparing the expression of human DNA topoisomerase I in KM71 and X33 strains of Pichia pastoris. Electron J Biotechnol. 21:9–17. 2016. View Article : Google Scholar

21 

Hong TB, Rahumatullah A, Yogarajah T, Ahmad M and Yin KB: Potential effects of chrysin on MDA-MB-231 cells. Int J Mol Sci. 11:1057–1069. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Xuan H, Li Z, Yan H, Sang Q, Wang K, He Q, Wang Y and Hu F: Antitumor activity of Chinese propolis in human breast cancer MCF-7 and MDA-MB-231 cells. Evid Based Complement Alternat Med. 2014:2801202014. View Article : Google Scholar : PubMed/NCBI

23 

Pereira C, Lopes-Rodrigues V, Coutinho I, Neves MP, Lima RT, Pinto M, Cidade H, Vasconcelos MH and Saraiva L: Potential small-molecule activators of caspase-7 identified using yeast-based caspase-3 and −7 screening assays. Eur J Pharm Sci. 54:8–16. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Bach S, Talarek N, Andrieu T, Vierfond JM, Mettey Y, Galons H, Dormont D, Meijer L, Cullin C and Blondel M: Isolation of drugs active against mammalian prions using a yeast-based screening assay. Nat Biotechnol. 21:1075–1081. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Liu X, Kramer JA, Swaffield JC, Hu Y, Chai G and Wilson AG: Development of a highthroughput yeast-based assay for detection of metabolically activated genotoxins. Mutat Res. 653:63–69. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Denny PW: Yeast: Bridging the gap between phenotypic and biochemical assays for high-throughput screening. Expert Opin Drug Discov. 16:1–8. 2018.

27 

Voisset C, Daskalogianni C, Contesse MA, Mazars A, Arbach H, Le Cann M, Soubigou F, Apcher S, Fåhraeus R and Blondel M: A yeast-based assay identifies drugs that interfere with immune evasion of the Epstein-Barr virus. Dis Model Mech. 7:435–444. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Sun Y, Wang Z, Tao J, Wang Y, Wu A, Yang Z, Wang K, Shi L, Chen Y and Guo D: Yeast-based assays for the high-throughput screening of inhibitors of coronavirus RNA cap guanine-N7-methyltransferase. Antiviral Res. 104:156–164. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Bilsland E, Sparkes A, Williams K, Moss HJ, de Clare M, Pir P, Rowland J, Aubrey W, Pateman R, Young M, et al: Yeast-based automated high-throughput screens to identify anti-parasitic lead compounds. Open Biol. 3:1201582013. View Article : Google Scholar : PubMed/NCBI

30 

Couplan E, Aiyar RS, Kucharczyk R, Kabala A, Ezkurdia N, Gagneur J, St Onge RP, Salin B, Soubigou F, Le Cann M, et al: A yeast-based assay identifies drugs active against human mitochondrial disorders. Proc Natl Acad Sci USA. 108:11989–11994. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Bovee TF, Thevis M, Hamers AR, Peijnenburg AA, Nielen MW and Schoonen WG: SERMs and SARMs: Detection of their activities with yeast-based bioassays. J Steroid Biochem Mol Biol. 118:85–92. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Alaamery MA, Wyman AR, Ivey FD, Allain C, Demirbas D, Wang L, Ceyhan O and Hoffman CS: New classes of PDE7 inhibitors identified by a fission yeast-based HTS. J Biomol Screen. 15:359–367. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Sangkaew A, Krungkrai J and Yompakdee C: Development of a high throughput yeast-based screening assay for human carbonic anhydrase isozyme II inhibitors. AMB Express. 8:1242018. View Article : Google Scholar : PubMed/NCBI

34 

Lichtenberg-Fraté H, Schmitt M, Gellert G and Ludwig J: A yeast-based method for the detection of cyto and genotoxicity. Toxicol In Vitro. 17:709–716. 2003. View Article : Google Scholar : PubMed/NCBI

35 

Chatterjee S, Majumder CB and Roy P: Development of a yeast-based assay to determine the (anti)androgenic contaminants from pulp and paper mill effluents in India. Environ Toxicol Pharmacol. 24:114–121. 2007. View Article : Google Scholar : PubMed/NCBI

36 

MacLean MJ, Llordella MM, Bot N and Picard D: A yeast-based assay reveals a functional defect of the Q488H polymorphism in human Hsp90alpha. Biochem Biophys Res Commun. 337:133–137. 2005. View Article : Google Scholar : PubMed/NCBI

37 

Chatterjee S, Kumar V, Majumder CB and Roy P: Screening of some anti-progestin endocrine disruptors using a recombinant yeast-based in vitro bioassay. Toxicol In Vitro. 22:788–798. 2008. View Article : Google Scholar : PubMed/NCBI

38 

Lubrano S, Comelli L, Piccirilli C, Marranci A, Dapporto F, Tantillo E, Gemignani F, Gutkind JS, Salvetti A, Chiorino G, et al: Development of a yeast-based system to identify new hBRAFV600E functional interactors. Oncogene. 38:1355–1366. 2019. View Article : Google Scholar : PubMed/NCBI

39 

Jacobs PP, Inan M, Festjens N, Haustraete J, Van Hecke A, Contreras R, Meagher MM and Callewaert N: Fed-batch fermentation of GM-CSF-producing glycoengineered Pichia pastoris under controlled specific growth rate. Microb Cell Fact. 9:932010. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

June 2019
Volume 19 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Xin, J., Wan Mahtar, W.N., Siah, P.C., Miswan, N., & Khoo, B.Y. (2019). Potential use of Pichia pastoris strain SMD1168H expressing DNA topoisomerase I in the screening of potential anti‑breast cancer agents. Molecular Medicine Reports, 19, 5368-5376. https://doi.org/10.3892/mmr.2019.10201
MLA
Xin, J., Wan Mahtar, W. N., Siah, P. C., Miswan, N., Khoo, B. Y."Potential use of Pichia pastoris strain SMD1168H expressing DNA topoisomerase I in the screening of potential anti‑breast cancer agents". Molecular Medicine Reports 19.6 (2019): 5368-5376.
Chicago
Xin, J., Wan Mahtar, W. N., Siah, P. C., Miswan, N., Khoo, B. Y."Potential use of Pichia pastoris strain SMD1168H expressing DNA topoisomerase I in the screening of potential anti‑breast cancer agents". Molecular Medicine Reports 19, no. 6 (2019): 5368-5376. https://doi.org/10.3892/mmr.2019.10201