PL EN


Preferences help
enabled [disable] Abstract
Number of results
2016 | 14 | 3 | 156–161
Article title

Salinomycyna – przełom w leczeniu raka jajnika?

Content
Title variants
EN
Salinomycin – a breakthrough in the treatment of ovarian cancer?
Languages of publication
EN PL
Abstracts
EN
It is believed that cancer stem cells are the primary cause of cancer chemotherapy resistance, metastasis and relapse. The cancer stem cells form a small population of cells present in the tumor (accounting for less than 2% of the tumor mass) and have properties which enable them to survive chemo- and radiotherapy. These cells have the ability to self-renew, do not undergo apoptosis, display overexpression of the ALDH1A1 enzyme and ABC genes which encode transport proteins, and furthermore make use of various signaling pathways (Wnt, Notch, Hedgehog). Cancer stem cells may be identified and isolated from the tumor based on the characteristic biomarkers (CD44+, CD133+, CD117+, BMi1, Oct-4, nestin). It has been demonstrated that salinomycin, an antibiotic obtained from Streptomyces albus, eliminates cancer stem cells, which are resistant to treatment with cytostatics. Salinomycin causes apoptosis of these cells through a number of mechanisms, including the disruption of the Na+/K+ ion balance in biological membranes, inhibition of the Wnt pathway and resistance to transporters, increase in the activity of caspases, activation of the MAPKp38 pathway and inhibition of the nuclear transcription factor NF-κB. Salinomycin has an effect on many types of cancer. It may turn out to be a breakthrough in the therapy of chemotherapy-resistant cancers.
PL
Uważa się, że główną przyczyną chemiooporności, przerzutów i nawrotów raka jajnika są komórki macierzyste raka. Jest to obecna w guzie mała populacja komórek (stanowiąca mniej niż 2% jego masy), których właściwości pozwalają im przetrwać chemio- i radioterapię. Komórki te mają zdolność do samoodnowy, nie podlegają apoptozie, wykazują nadekspresję genów ABC kodujących białka transportowe, enzymu ALDH1A1 i korzystają z różnych szlaków sygnałowania (Wnt, Notch, Hedgehog). Komórki macierzyste raka można zidentyfikować oraz izolować z guza na podstawie charakterystycznych biomarkerów (CD44+, CD133+, CD117+, BMi1, Oct-4, nestyna). Wykazano, że salinomycyna, antybiotyk uzyskany ze Streptomyces albus, eliminuje komórki macierzyste raka, które są oporne na leczenie cytostatykami. Salinomycyna powoduje apoptozę tych komórek poprzez wiele mechanizmów, w tym poprzez zakłócenie jonowego bilansu Na+/K+ w błonach biologicznych, hamowanie szlaku Wnt i oporności na działanie transporterów, wzrost aktywności kaspaz, aktywację szlaku MAPKp38 oraz hamowanie jądrowego czynnika transkrypcyjnego NF-κB. Salinomycyna jest aktywna w wielu rodzajach nowotworów. Może okazać się przełomem w terapii nowotworów chemioopornych.
Discipline
Publisher

Year
Volume
14
Issue
3
Pages
156–161
Physical description
Contributors
  • Zakład Biochemii, Wydział Chemii, Uniwersytet im. Adama Mickiewicza w Poznaniu, Poznań, Polska
  • Katedra i Klinika Onkologii, Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu, ul. Szamarzewskiego 82/84, 60-569 Poznań
author
  • Katedra i Klinika Onkologii, Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu, Poznań, Polska
author
  • Klinika Ginekologii Operacyjnej, Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu, Poznań, Polska
  • Klinika Ginekologii Operacyjnej, Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu, Poznań, Polska
  • Katedra i Klinika Onkologii, Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu, Poznań, Polska
References
  • 1. Ferlay J, Soerjomataram J, Ervik M et al.: Ovarian cancer statistics. IARC, 2014. Available from: http://globocan.iarc.fr [cited 16 January 2015].
  • 2. Chen J, Wang J, Zhang Y et al.: Observation of ovarian cancer stem cell behavior and investigation of potential mechanisms of drug resistance in three-dimensional cell culture. J Biosci Bioeng 2014; 118: 214–222.
  • 3. Craveiro V, Yang-Hartwich Y, Holmberg JC et al.: Phenotypic modifications in ovarian cancer stem cells following Paclitaxel treatment. Cancer Med 2013; 2: 751–762.
  • 4. Shah MM, Landen CN: Ovarian cancer stem cells: are they real and why are they important? Gynecol Oncol 2014; 132: 483–489.
  • 5. Niero EL, Rocha-Sales B, Lauand C et al.: The multiple facets of drug resistance: one history, different approaches. J Exp Clin Cancer Res 2014; 33: 37.
  • 6. Tomao F, Papa A, Rossi L et al.: Emerging role of cancer stem cells in the biology and treatment of ovarian cancer: basic knowledge and therapeutic possibilities for an innovative approach. J Exp Clin Cancer Res 2013; 32: 48.
  • 7. Clarke MF, Dick JE, Dirks PB et al.: Cancer stem cells – perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 2006; 66: 9339–9344.
  • 8. Bapat SA, Mali AM, Koppikar CB et al.: Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res 2005; 65: 3025–3029.
  • 9. Visvader JE, Lindeman GJ: Cancer stem cells: current status and evolving complexities. Cell Stem Cell 2012; 10: 717–728.
  • 10. Massard C, Deutsch E, Soria JC: Tumour stem cell-targeted treatment: elimination or differentiation. Ann Oncol 2006; 17: 1620–1624.
  • 11. Dean M, Fojo T, Bates S: Tumour stem cells and drug resistance. Nat Rev Cancer 2005; 5: 275–284.
  • 12. Zhou N, Wu X, Yang B et al.: Stem cell characteristics of dormant cells and cisplatin-induced effects on the stemness of epithelial ovarian cancer cells. Mol Med Rep 2014; 10: 2495–2504.
  • 13. Klonisch T, Wiechec E, Hombach-Klonisch S et al.: Cancer stem cell markers in common cancers – therapeutic implications. Trends Mol Med 2008; 14: 450–460.
  • 14. Kurman RJ, Shih IeM: The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol 2010; 34: 433–443.
  • 15. Liao J, Qian F, Tchabo N et al.: Ovarian cancer spheroid cells with stem cell-like properties contribute to tumor generation, metastasis and chemotherapy resistance through hypoxia-resistant metabolism. PLoS One 2014; 9: e84941.
  • 16. Prud’homme GJ: Cancer stem cells and novel targets for antitumor strategies. Curr Pharm Des 2012; 18: 2838–2849.
  • 17. Zeng J, Ruan J, Luo L et al.: Molecular portraits of heterogeneity related to cancer stem cells in human ovarian cancer. Int J Gynecol Cancer 2014; 24: 29–35.
  • 18. Yu ZH, Liu T, Zhao YH et al.: Cisplatin targets the stromal cellderived factor-1-CXC chemokine receptor type 4 axis to suppress metastasis and invasion of ovarian cancer-initiating cells. Tumour Biol 2014; 35: 4637–4644.
  • 19. Catalano V, Turdo A, Di Franco S et al.: Tumor and its microenvironment: a synergistic interplay. Semin Cancer Biol 2013; 23: 522–532.
  • 20. Nagano O, Okazaki S, Saya H: Redox regulation in stem-like cancer cells by CD44 variant isoforms. Oncogene 2013; 32: 5191–5198.
  • 21. Bourguignon LY, Peyrollier K, Xia W et al.: Hyaluronan-CD44 interaction activates stem cell marker Nanog, Stat-3-mediated MDR1 gene expression, and ankyrin-regulated multidrug efflux in breast and ovarian tumor cells. J Biol Chem 2008; 283: 17635–17651.
  • 22. Silva IA, Bai S, McLean K et al.: Aldehyde dehydrogenase in combination with CD133 defines angiogenic ovarian cancer stem cells that portend poor patient survival. Cancer Res 2011; 71: 3991–4001.
  • 23. Bapat SA: Human ovarian cancer stem cells. Reproduction 2010; 140: 33–41.
  • 24. Neradil J, Veselska R: Nestin as a marker of cancer stem cells. Cancer Sci 2015; 106: 803–811.
  • 25. Miyazaki Y, Shibuya M, Sugawara H et al.: Salinomycin, a new polyether antibiotic. J Antibiot (Tokyo) 1974; 27: 814–821.
  • 26. Gupta PB, Onder TT, Jiang G et al.: Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 2009; 138: 645–659.
  • 27. Naujokat C, Fuchs D, Opelz G: Salinomycin in cancer: a new mission for an old agent. Mol Med Rep 2010; 3: 555–559.
  • 28. Lu D, Choi MY, Yu J et al.: Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells. Proc Natl Acad Sci U S A 2011; 108: 13253–13257.
  • 29. Eyler CE, Rich JN: Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol 2008; 26: 2839–2845.
  • 30. Riccioni R, Dupuis ML, Bernabei M et al.: The cancer stem cell selective inhibitor salinomycin is a p-glycoprotein inhibitor. Blood Cells Mol Dis 2010; 45: 86–92.
  • 31. Kim JH, Yoo HI, Kang HS et al.: Salinomycin sensitizes antimitotic drugs-treated cancer cells by increasing apoptosis via the prevention of G2 arrest. Biochem Biophys Res Commun 2012; 418: 98–103.
  • 32. Antoszczak M, Huczyński A: Anticancer activity of polyether ionophore-salinomycin. Anticancer Agents Med Chem 2015; 15: 575–591.
  • 33. Parajuli B, Shin SJ, Kwon SH et al.: Salinomycin induces apoptosis via death receptor-5 up-regulation in cisplatin-resistant ovarian cancer cells. Anticancer Res 2013; 33: 1457–1462.
  • 34. Parajuli B, Lee HG, Kwon SH et al.: Salinomycin inhibits Akt/ NF-κB and induces apoptosis in cisplatin resistant ovarian cancer cells. Cancer Epidemiol 2013; 37: 512–517.
  • 35. Zhang B, Wang X, Cai F et al.: Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation. Oncol Rep 2013; 29: 1371–1378.
  • 36. Chung H, Kim YH, Kwon M et al.: The effect of salinomycin on ovarian cancer stem-like cells. Obstet Gynecol Sci 2016; 59: 261–268.
  • 37. Kaplan F, Teksen F: Apoptotic effects of salinomycin on human ovarian cancer cell line (OVCAR-3). Tumour Biol 2016; 37:3897–3903.
Document Type
review
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.psjd-c9bf5777-9853-49c6-8f35-d9b248882814
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.