CYTOTOXIC AND ANTI-MIGRATORY ACTIVITIES FROM HYDROALCOHOLIC EXTRACT OF Euphorbia lactea Haw. AGAINST HN22 CELL LINE
DOI:
https://doi.org/10.14456/tbps/2018.1Keywords:
cytotoxic, anticancer, antimetastatic, Euphorbia lacteaAbstract
Euphorbiaceae is a botanical family of evolutionarily and morphologically distinct group of plants. Many euphorbias have been associated with diverse pharmacological properties including anticancer activity. Euphorbia lactea Haw. can be found naturally throughout Thailand; however, its anticancer activity remains largely unexplored. Here, we screened hydroalcoholic extract of E. lactea for its anticancer potentials, focusing on cytotoxic and anti-migratory activities using a migratory competent head and neck cancer cell line HN22 as an in vitro model. We detected statistically significant and dose-dependent cytotoxic activity of E. lactea hydroalcoholic extract against HN22 cells through MTT assay. Flow cytometry analysis of HN22 cells treated with the extract revealed an increase in sub-G1 population, suggesting that the cytotoxic effect of
E. lactea hydroalcoholic extract likely involved an initiation of apoptosis in this cell line. Additionally, through wound-healing assays, we unprecedentedly reported an anti-migratory activity against HN22 cells from E. lactea hydroalcoholic extract. Together, exhibiting two attractive attributes i.e. cytotoxic and anti-migratory activities toward HN22 cells, our results identified E. lactea as a promising candidate medicinal plant for further investigations to unlock its anticancer potentials.
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33. Zhang JY, Huang WJ, Sun HM, Liu Y, Zhao XQ, Tang SL, et al. Structure Identification and In Vitro Anticancer Activity of Lathyrol-3-phenylacetate-5,15-diacetate. Molecules.2017; 22(9).
34. Justus CR, Leffler N, Ruiz-Echevarria M, Yang LV. In vitro Cell Migration and Invasion Assays. J Vis Exp. 2014(88):e51046.
35. Shin SY, Kim CG, Jung YJ, Jung Y, Jung H, Im J, et al. Euphorbia humifusa Willd exerts inhibition of breast cancer cell invasion and metastasis through inhibition of TNF alpha- induced MMP-9 expression. BMC Complement Altern Med. 2016;16(1):413.
36. Ko YS, Lee WS, Joo YN, Choi YH, Kim GS, Jung JM, et al. Polyphenol mixtures of Euphorbia supina the inhibit invasion and metastasis of highly metastatic breast cancer MDA-MB- 231 cells. Oncol Rep. 2015;34(6):3035-42.
37. Sun C, Cui H, Yang H, Du X, Yue L, Liu J, et al. Anti-metastatic effect of jolkinolide B and the mechanism of activity in breast cancer MDA-MB-231 cells. Oncol Lett. 2015;10(2):1117- 22.
38. Dong MH, Zhang Q, Wang YY, Zhou BS, Sun YF, Fu Q. Euphorbia fischeriana Steud inhibits malignant melanoma via modulation of the phosphoinositide-3-kinase/Akt signaling pathway. Exp Ther Med. 2016;11(4):1475-80.
2. Saini VK, Sewal RK, Ahmad Y, Medhi B. Prospective Observational Study of Adverse Drug Reactions of Anticancer Drugs Used in Cancer Treatment in a Tertiary Care Hospital. Indian J Pharm Sci. 2015;77(6):687-93.
3. Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer. 2013;13(10):714-26.
4. Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, et al. Drug Resistance in Cancer: An Overview. Cancers. 2014;6(3):1769-92.
5. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: a cancer journal for clinicians. 2016;66(1):7-30.
6. Bogenrieder T, Herlyn M. Axis of evil: molecular mechanisms of cancer metastasis. Oncogene. 2003;22(42):6524-36.
7. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-74.
8. Atanasov AG, Waltenberger B, Pferschy-Wenzig E-M, Linder T, Wawrosch C, Uhrin P, et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol Adv. 2015;33(8):1582-614.
9. Saklani A, Kutty S. Plant-derived compounds in clinical trials. Drug Discov Today. 2008;13(3-4):161-71.
10. Mishra BB, Tiwari VK. Natural products: an evolving role in future drug discovery. Eur J Med Chem. 2011;46(10):4769-807.
11. Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. Journal of ethnopharmacology. 2005;100(1-2):72-9.
12. Ernst M, Grace OM, Saslis-Lagoudakis CH, Nilsson N, Simonsen HT, Ronsted N. Global medicinal uses of Euphorbia L. (Euphorbiaceae). J Ethnopharmacol. 2015;176:90-101.
13. Shi QW, Su XH, Kiyota H. Chemical and pharmacological research of the plants in genus Euphorbia. Chem Rev. 2008;108(10):4295-327.
14. Man S, Gao W, Wei C, Liu C. Anticancer drugs from traditional toxic Chinese medicines. Phytother Res. 2012;26(10):1449-65.
15. Fernandez-Arche A, Saenz MT, Arroyo M, de la Puerta R, Garcia MD. Topical anti-inflammatory effect of tirucallol, a triterpene isolated from Euphorbia lactea latex. Phytomedicine. 2010;17(2):146-8.
16. El Manawaty M, Fayad W, El-Fiky NM, Wassel GM, El-Menshawi B. High-throughput screening of 75 euphorbiaceae and myrtaceae plant extracts for in-vitro antitumor and pro-apoptotic activities on human tumor cell lines, and lethality to brine shrimp. Int J Pharm Pharm Sci. 2013;5(Suppl 2):178-83.
17. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Meth. 2012;9(7):671-5.
18. Franco-Salla GB, Prates J, Cardin LT, Dos Santos AR, Silva WA, Jr., da Cunha BR, et al. Euphorbia tirucalli modulates gene expression in larynx squamous cell carcinoma. BMC Complement Altern Med. 2016;16:136.
19. Fan L, Xiao Q, Chen Y, Chen G, Duan J, Tao W. Pekinenin E Inhibits the Growth of Hepatocellular Carcinoma by Promoting Endoplasmic Reticulum Stress Mediated Cell Death. Front Pharmacol. 2017;8:424.
20. Ma H, Yang S, Lu H, Zhang Y. Bioassay-guided Separation of Anti-tumor Components from Euphorbia kansui by Means of Two-dimensional Preparative High Performance Liquid Chromatography and Real-time Cell Analysis. Anal Sci. 2016;32(5):581-6.
21. Song Y, Jeong SW, Lee WS, Park S, Kim YH, Kim GS, et al. Determination of Polyphenol Components of Korean Prostrate Spurge (Euphorbia supina) by Using Liquid Chromatography-Tandem Mass Spectrometry: Overall Contribution to Antioxidant Activity. J Analytical Methods Chem. 2014;2014:418690.
22. Nabatchian F, Moradi A, Aghaei M, Ghanadian M, Jafari SM, Tabesh S. New 6(17)-epoxylathyrane diterpene: aellinane from Euphorbia aellenii induces apoptosis via mitochondrial pathway in ovarian cancer cell line. Toxicol Mech Methods. 2017;27(8):622-30.
23. Bahmani B, Keyvanloo Shahrestanaki M, Ghanadian M, Hajiahmadi S, Aghaei M. Jatropha-6(17),11E-diene class derivatives induce apoptosis effects in OVCAR-3 and Caov-4 ovarian cancer cell lines via mitochondrial pathway. Biochem Cell Biol. 2017.
24. Al-Faifi ZI, Masrahi YS, Aly MS, Al-Turki TA, Dardeer T. Evaluation of Cytotoxic and Genotoxic Effects of Euphorbia Triaculeata Forssk. Extract. Asian Pac J Cancer Prev. 2017;18(3):771-7.
25. Fu Z, Han X, Du J, Han X, Liu W, Shao S, et al. Euphorbia lunulata extract acts on multidrug resistant gastric cancer cells to inhibit cell proliferation, migration and invasion, arrest cell cycle progression, and induce apoptosis. J Ethno-pharmacol. 2017.
26. Lin M, Tang S, Zhang C, Chen H, Huang W, Liu Y, et al. Euphorbia factor L2 induces apoptosis in A549 cells through the mitochondrial pathway. Acta Pharm Sin B. 2017;7(1):59-64.
27. Munro B, Vuong QV, Chalmers AC, Goldsmith CD, Bowyer MC, Scarlett CJ. Phytochemical, Antioxidant and Anti-Cancer Properties of Euphorbia tirucalli Methanolic and Aqueous Extracts. Antioxidants (Basel, Switzerland). 2015;4(4):647-61.
28. Aliomrani M, Jafarian A, Zolfaghari B. Phytochemical Screening and Cytotoxic Evaluation of Euphorbia turcomanica on Hela and HT-29 Tumor Cell Lines. Adv Biomed Res. 2017;6:68.
29. Darzynkiewicz Z, Bruno S, Del Bino G, Gorczyca W, Hotz MA, Lassota P, et al. Features of apoptotic cells measured by flow cytometry. Cytometry. 1992;13(8):795-808.
30. Fu Z, Han X, Du J, Han X, Liu W, Shao S, et al. Euphorbia lunulata extract acts on multidrug resistant gastric cancer cells to inhibit cell proliferation, migration and invasion, arrest cell cycle progression, and induce apoptosis. J Ethno-pharmacol. 2017;212:8-17.
31. Fallahian F, Ghanadian M, Aghaei M, Zarei SM. Induction of G2/M phase arrest and apoptosis by a new tetrahydroingenol diterpenoid from Euphorbia erythradenia Bioss. in melanoma cancer cells. Biomed Pharmacother. 2017;86:334-42.
32. Liu M, Zhang W, Wang G, Song X, Zhao X, Wang X, et al. 13-Oxyingenol dodecanoate, a cytotoxic ingenol derivative, induces mitochondrial apoptosis and caspase-dependent Akt decrease in K562 cells. Tumour Biol. 2016;37(5):6227-38.
33. Zhang JY, Huang WJ, Sun HM, Liu Y, Zhao XQ, Tang SL, et al. Structure Identification and In Vitro Anticancer Activity of Lathyrol-3-phenylacetate-5,15-diacetate. Molecules.2017; 22(9).
34. Justus CR, Leffler N, Ruiz-Echevarria M, Yang LV. In vitro Cell Migration and Invasion Assays. J Vis Exp. 2014(88):e51046.
35. Shin SY, Kim CG, Jung YJ, Jung Y, Jung H, Im J, et al. Euphorbia humifusa Willd exerts inhibition of breast cancer cell invasion and metastasis through inhibition of TNF alpha- induced MMP-9 expression. BMC Complement Altern Med. 2016;16(1):413.
36. Ko YS, Lee WS, Joo YN, Choi YH, Kim GS, Jung JM, et al. Polyphenol mixtures of Euphorbia supina the inhibit invasion and metastasis of highly metastatic breast cancer MDA-MB- 231 cells. Oncol Rep. 2015;34(6):3035-42.
37. Sun C, Cui H, Yang H, Du X, Yue L, Liu J, et al. Anti-metastatic effect of jolkinolide B and the mechanism of activity in breast cancer MDA-MB-231 cells. Oncol Lett. 2015;10(2):1117- 22.
38. Dong MH, Zhang Q, Wang YY, Zhou BS, Sun YF, Fu Q. Euphorbia fischeriana Steud inhibits malignant melanoma via modulation of the phosphoinositide-3-kinase/Akt signaling pathway. Exp Ther Med. 2016;11(4):1475-80.
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