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Tomentosin shows anticancer effect on U87 human glioblastoma multiforme cells

Year 2021, Volume: 2 Issue: 2, 23 - 26, 31.12.2021
https://doi.org/10.51539/biotech.1027492

Abstract

Glioblastoma multiforme (GBM) is one of the most common brain tumors. Chemotherapy, radiotherapy and surgical resection are methods used in GBM treatment, however, the investigation of possible anticancer effects of low-toxicity natural products on various cancer cells, including GBM, leads to promising results. In this study, it was aimed to investigate anticancer effect of tomentosin, which is a sesquiterpene lactone, on U87 human GBM cells. The cytotoxic effect of tomentosin was evaluated by XTT assay. The concentration of tomentosin that inhibits 50% cell viability (IC50) was determined by the results from XTT, and, in further analyzes cells were treated with tomentosin at IC50 concentration. Then, total RNA isolation and cDNA synthesis were performed in control and dose groups, and, the possible anticancer effect of tomentosin was determined by evaluating the expression levels of important genes associated with apoptosis and metastasis by qPCR analysis. In addition, the effect of tomentosin on the colony forming capacity of GBM cells was evaluated by colony formation assay. According to our results, IC50 dose of tomentosin was found to be 28.8 µM in U87 cells for 48 hours. When compared to the control group, tomentosin increased expression of BAX, CASP3, CASP8, CASP9, CYCS, FADD, TNF, TNFR1, TNFR2 and TIMP2 genes. And, tomantosin significantly decreased colony forming capacity of U87 cells. In conclusion, it is thought that tomentosin exerts its anticancer effect by changing the expression levels of genes associated with apoptosis and metastasis in U87 GBM cells.

References

  • Arpino V, Brock M, Gill SE (2015) The role of TIMPs in regulation of extracellular matrix proteolysis. Matrix Biol 44-46:247-54.
  • Babaei G, Aliarab A, Abroon S, Rasmi Y, Aziz SG (2018) Application of sesquiterpene lactone: A new promising way for cancer therapy based on anticancer activity. Biomed Pharmacother 106:239-246.
  • Bagherian A, Mardani R, Roudi B, Taghizadeh M, Banfshe HR, Ghaderi A, Davoodvandi A, Shamollaghamsari S, Hamblin MR, Mirzaei H (2020) Combination Therapy with Nanomicellar-Curcumin and Temozolomide for In Vitro Therapy of Glioblastoma Multiforme via Wnt Signaling Pathways. J Mol Neurosci 70(10):1471-1483.
  • Cafarchia C, De Laurentis N, Milillo MA, Losacco V, Puccini V (2001) Fungistatic activity of a sesquiterpene lactone (tomentosin) isolated from fresh Inula viscosa (Asteraceae) flowers from the Puglia region. Parassitologia 43(3):117-21
  • Cha GD, Kang T, Baik S, Kim D, Choi SH, Hyeon T, Kim DH (2020) Advances in drug delivery technology for the treatment of glioblastoma multiforme. J Control Release 328:350-367.
  • Choi J, Kim G, Cho SB, Hyung-Jun I (2020) Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme. J Nanobiotechnol 18, 122.
  • El Omari N, El Menyiy N, Zengin G, Goh BH, Gallo M, Montesano D, Naviglio D, Bouyahya A (2021) Anticancer and Anti-Inflammatory Effects of Tomentosin: Cellular and Molecular Mechanisms. Separations 8, 207.
  • Fulda S, Debatin KM (2006) Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25, 4798–4811.
  • Kashyap D, Tuli HS, Yerer MB, Sharma A, Sak K, Srivastava S, Pandey A, Garg VK, Sethi G, Bishayee A (2021) Natural product-based nanoformulations for cancer therapy: Opportunities and challenges. Semin Cancer Biol 69:5-23.
  • Lee CM, Lee J, Nam MJ, Choi YS, Park SH (2019) Tomentosin Displays Anti-Carcinogenic Effect in Human Osteosarcoma MG-63 Cells via the Induction of Intracellular Reactive Oxygen Species. Int J Mol Sci 20(6):1508.
  • Merghoub N, El Btaouri H, Benbacer L, Gmouh S, Trentesaux C, Brassart B, Attaleb M, Madoulet C, Wenner T, Amzazi S, Morjani H, El Mzibri M (2017) Tomentosin Induces Telomere Shortening and Caspase-Dependant Apoptosis in Cervical Cancer Cells. J Cell Biochem 118(7):1689-1698.
  • Park HH, Kim SG, Kim MJ, Lee J, Choi BK, Jin MH, Lee E (2014) Suppressive effect of tomentosin on the production of inflammatory mediators in RAW264.7 cells. Biol Pharm Bull 37(7):1177-83.
  • Park MN, Song HS, Kim M, Lee MJ, Cho W, Lee HJ, Hwang CH, Kim S, Hwang Y, Kang B, Kim B (2017) Review of Natural Product-Derived Compounds as Potent Antiglioblastoma Drugs. Biomed Res Int 2017:8139848.
  • Tan AC, Ashley DM, López GY, Malinzak M, Friedman HS, Khasraw M (2020) Management of glioblastoma: State of the art and future directions. CA Cancer J Clin 70(4):299-312.
  • Vengoji R, Macha MA, Batra SK, Shonka NA (2018) Natural products: a hope for glioblastoma patients. Oncotarget 9: 22194-22219.
  • Virdis P, Marchesi I, Fiorentino FP, Migheli R, Sanna L, Bordoni V, Pintore G, Galleri G, Muroni MR, Bagella L, Fozza C, De Miglio MR, Podda L (2021) Tomentosin a Sesquiterpene Lactone Induces Antiproliferative and Proapoptotic Effects in Human Burkitt Lymphoma by Deregulation of Anti- and Pro-Apoptotic Genes. Life 11(11):1128.
  • Yang H, Zhao H, Dong X, Yang Z, Chang W (2020) Tomentosin induces apoptotic pathway by blocking inflammatory mediators via modulation of cell proteins in AGS gastric cancer cell line. J Biochem Mol Toxicol 34(8):e22501.
  • Yang L, Xie J, Almoallim HS, Alharbi SA, Chen Y (2021) Tomentosin inhibits cell proliferation and induces apoptosis in MOLT-4 leukemia cancer cells through the inhibition of mTOR/PI3K/Akt signaling pathway. J Biochem Mol Toxicol 35(4):e22719.
  • Yu SH, Lee CM, Ha SH, Lee J, Jang KY, Park SH (2021) Induction of cell cycle arrest and apoptosis by tomentosin in hepatocellular carcinoma HepG2 and Huh7 cells. Hum Exp Toxicol 40(2):231-244.
Year 2021, Volume: 2 Issue: 2, 23 - 26, 31.12.2021
https://doi.org/10.51539/biotech.1027492

Abstract

References

  • Arpino V, Brock M, Gill SE (2015) The role of TIMPs in regulation of extracellular matrix proteolysis. Matrix Biol 44-46:247-54.
  • Babaei G, Aliarab A, Abroon S, Rasmi Y, Aziz SG (2018) Application of sesquiterpene lactone: A new promising way for cancer therapy based on anticancer activity. Biomed Pharmacother 106:239-246.
  • Bagherian A, Mardani R, Roudi B, Taghizadeh M, Banfshe HR, Ghaderi A, Davoodvandi A, Shamollaghamsari S, Hamblin MR, Mirzaei H (2020) Combination Therapy with Nanomicellar-Curcumin and Temozolomide for In Vitro Therapy of Glioblastoma Multiforme via Wnt Signaling Pathways. J Mol Neurosci 70(10):1471-1483.
  • Cafarchia C, De Laurentis N, Milillo MA, Losacco V, Puccini V (2001) Fungistatic activity of a sesquiterpene lactone (tomentosin) isolated from fresh Inula viscosa (Asteraceae) flowers from the Puglia region. Parassitologia 43(3):117-21
  • Cha GD, Kang T, Baik S, Kim D, Choi SH, Hyeon T, Kim DH (2020) Advances in drug delivery technology for the treatment of glioblastoma multiforme. J Control Release 328:350-367.
  • Choi J, Kim G, Cho SB, Hyung-Jun I (2020) Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme. J Nanobiotechnol 18, 122.
  • El Omari N, El Menyiy N, Zengin G, Goh BH, Gallo M, Montesano D, Naviglio D, Bouyahya A (2021) Anticancer and Anti-Inflammatory Effects of Tomentosin: Cellular and Molecular Mechanisms. Separations 8, 207.
  • Fulda S, Debatin KM (2006) Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25, 4798–4811.
  • Kashyap D, Tuli HS, Yerer MB, Sharma A, Sak K, Srivastava S, Pandey A, Garg VK, Sethi G, Bishayee A (2021) Natural product-based nanoformulations for cancer therapy: Opportunities and challenges. Semin Cancer Biol 69:5-23.
  • Lee CM, Lee J, Nam MJ, Choi YS, Park SH (2019) Tomentosin Displays Anti-Carcinogenic Effect in Human Osteosarcoma MG-63 Cells via the Induction of Intracellular Reactive Oxygen Species. Int J Mol Sci 20(6):1508.
  • Merghoub N, El Btaouri H, Benbacer L, Gmouh S, Trentesaux C, Brassart B, Attaleb M, Madoulet C, Wenner T, Amzazi S, Morjani H, El Mzibri M (2017) Tomentosin Induces Telomere Shortening and Caspase-Dependant Apoptosis in Cervical Cancer Cells. J Cell Biochem 118(7):1689-1698.
  • Park HH, Kim SG, Kim MJ, Lee J, Choi BK, Jin MH, Lee E (2014) Suppressive effect of tomentosin on the production of inflammatory mediators in RAW264.7 cells. Biol Pharm Bull 37(7):1177-83.
  • Park MN, Song HS, Kim M, Lee MJ, Cho W, Lee HJ, Hwang CH, Kim S, Hwang Y, Kang B, Kim B (2017) Review of Natural Product-Derived Compounds as Potent Antiglioblastoma Drugs. Biomed Res Int 2017:8139848.
  • Tan AC, Ashley DM, López GY, Malinzak M, Friedman HS, Khasraw M (2020) Management of glioblastoma: State of the art and future directions. CA Cancer J Clin 70(4):299-312.
  • Vengoji R, Macha MA, Batra SK, Shonka NA (2018) Natural products: a hope for glioblastoma patients. Oncotarget 9: 22194-22219.
  • Virdis P, Marchesi I, Fiorentino FP, Migheli R, Sanna L, Bordoni V, Pintore G, Galleri G, Muroni MR, Bagella L, Fozza C, De Miglio MR, Podda L (2021) Tomentosin a Sesquiterpene Lactone Induces Antiproliferative and Proapoptotic Effects in Human Burkitt Lymphoma by Deregulation of Anti- and Pro-Apoptotic Genes. Life 11(11):1128.
  • Yang H, Zhao H, Dong X, Yang Z, Chang W (2020) Tomentosin induces apoptotic pathway by blocking inflammatory mediators via modulation of cell proteins in AGS gastric cancer cell line. J Biochem Mol Toxicol 34(8):e22501.
  • Yang L, Xie J, Almoallim HS, Alharbi SA, Chen Y (2021) Tomentosin inhibits cell proliferation and induces apoptosis in MOLT-4 leukemia cancer cells through the inhibition of mTOR/PI3K/Akt signaling pathway. J Biochem Mol Toxicol 35(4):e22719.
  • Yu SH, Lee CM, Ha SH, Lee J, Jang KY, Park SH (2021) Induction of cell cycle arrest and apoptosis by tomentosin in hepatocellular carcinoma HepG2 and Huh7 cells. Hum Exp Toxicol 40(2):231-244.
There are 19 citations in total.

Details

Primary Language English
Subjects Biochemistry and Cell Biology (Other)
Journal Section Research Articles
Authors

İlknur Çınar Ayan 0000-0002-8763-0480

Ebru Güçlü 0000-0001-5330-6159

Hatice Gul Dursun 0000-0001-5115-4681

Hasibe Vural 0000-0003-2564-7807

Publication Date December 31, 2021
Acceptance Date December 21, 2021
Published in Issue Year 2021 Volume: 2 Issue: 2

Cite

APA Çınar Ayan, İ., Güçlü, E., Dursun, H. G., Vural, H. (2021). Tomentosin shows anticancer effect on U87 human glioblastoma multiforme cells. Bulletin of Biotechnology, 2(2), 23-26. https://doi.org/10.51539/biotech.1027492
AMA Çınar Ayan İ, Güçlü E, Dursun HG, Vural H. Tomentosin shows anticancer effect on U87 human glioblastoma multiforme cells. Bull. Biotechnol. December 2021;2(2):23-26. doi:10.51539/biotech.1027492
Chicago Çınar Ayan, İlknur, Ebru Güçlü, Hatice Gul Dursun, and Hasibe Vural. “Tomentosin Shows Anticancer Effect on U87 Human Glioblastoma Multiforme Cells”. Bulletin of Biotechnology 2, no. 2 (December 2021): 23-26. https://doi.org/10.51539/biotech.1027492.
EndNote Çınar Ayan İ, Güçlü E, Dursun HG, Vural H (December 1, 2021) Tomentosin shows anticancer effect on U87 human glioblastoma multiforme cells. Bulletin of Biotechnology 2 2 23–26.
IEEE İ. Çınar Ayan, E. Güçlü, H. G. Dursun, and H. Vural, “Tomentosin shows anticancer effect on U87 human glioblastoma multiforme cells”, Bull. Biotechnol., vol. 2, no. 2, pp. 23–26, 2021, doi: 10.51539/biotech.1027492.
ISNAD Çınar Ayan, İlknur et al. “Tomentosin Shows Anticancer Effect on U87 Human Glioblastoma Multiforme Cells”. Bulletin of Biotechnology 2/2 (December 2021), 23-26. https://doi.org/10.51539/biotech.1027492.
JAMA Çınar Ayan İ, Güçlü E, Dursun HG, Vural H. Tomentosin shows anticancer effect on U87 human glioblastoma multiforme cells. Bull. Biotechnol. 2021;2:23–26.
MLA Çınar Ayan, İlknur et al. “Tomentosin Shows Anticancer Effect on U87 Human Glioblastoma Multiforme Cells”. Bulletin of Biotechnology, vol. 2, no. 2, 2021, pp. 23-26, doi:10.51539/biotech.1027492.
Vancouver Çınar Ayan İ, Güçlü E, Dursun HG, Vural H. Tomentosin shows anticancer effect on U87 human glioblastoma multiforme cells. Bull. Biotechnol. 2021;2(2):23-6.