Ferula gummosa gum exerts cytotoxic effects against human malignant glioblastoma multiforme in vitro

Amir R. Afshari , Seyed Hadi Mousavi, Golrokh Mousavi, Sanam Daneshpour Moghadam, Abolfazl Maghrouni, Hossein Javid, Zahra Tayarani-Najaran, Bahram Bibak, Hamid Mollazadeh, Azar Hosseini

Abstract


Background and purpose: Ferula gummosa (F. gummosa), a potent medicinal herb, has been shown to possess anticancer activities in vitro. The present examination evaluated the cytotoxic and apoptogenic impacts of F. gummosa gum on the U87 glioblastoma cells.

Experimental approach: MTT assay to determine the cell viability, flow cytometry by annexin                              V/FITC-PI to apoptosis evaluation, reactive oxygen species (ROS) assay, and quantitative RT-PCR were performed.

Findings / Results: The results revealed that F. gummosa inhibited the growth of U87 cells in a concentration- and time-dependent manner with IC50 values of 115, 82, and 52 μg/mL obtained for 24, 48, and 72 h post-treatment, respectively. It was also identified that ROS levels significantly decreased following 4, 12,                          and 24 h after treatment. The outcomes of flow cytometry analysis suggested that F. gummosa induced                             a sub-G1 peak which translated to apoptosis in a concentration-dependent manner. Further examination revealed that F. gummosa upregulated Bax/Bcl-2 ratio and p53 genes at mRNA levels.

Conclusion and implications: Collectively, these findings indicate that sub-G1 apoptosis and its related genes may participate in the cytotoxicity of F. gummosa gum in U87 cells.


Keywords


Apoptosis; Bax; Bcl-2; Ferula gummosa; Glioblastoma.

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References


Hou LC, Veeravagu A, Hsu AR, Tse VCK. Recurrent glioblastoma multiforme: a review of natural history and management options. Neurosurg Focus. 2006;20(4):E3,1-9. DOI: 10.3171/foc.2006.20.4.2.

Jalili-Nik M, Sabri H, Zamiri E, Soukhtanloo M, Roshan MK, Hosseini A, et al. Cytotoxic effects of Ferula Latisecta on human glioma U87 cells. Drug Res (Stuttg). 2019;69(12):665-670.DOI: 10.1055/a-0986-6543.

Zhao M, Straten DV, Broekman MLD, Preat V, Schiffelers RM. Nanocarrier-based drug combination therapy for glioblastoma. Theranostics. 2020;10(3):1355-1372. DOI: 10.7150/thno.38147.

Khajeh E, Rasmi Y, Kheradmand F, Malekinejad H, Aramwit P, Saboory E, et al. Crocetin suppresses the growth and migration in HCT-116 human colorectal cancer cells by activating the p-38 MAPK signaling pathway. Res Pharm Sci. 2020;15(6):592-601.DOI: 10.4103/1735-5362.301344.

Iranmanesh M, Mohebbati R, Forouzanfar F, Karimi Roshan M, Ghorbani A, Jalili Nik M, et al. In vivo and in vitro effects of ethanolic extract of Trigonella foenum-graecum L. seeds on proliferation, angiogenesis and tube formation of endothelial cells. Res Pharm Sci. 2018;13(4):343-352. DOI: 10.4103/1735-5362.235161.

Zhou GS, Song LJ, Yang B. Isoliquiritigenin inhibits proliferation and induces apoptosis of U87 human glioma cells in vitro. Mol Med Rep. 2013;7(2):531-536.DOI: 10.3892/mmr.2012.1218.

Afshari AR, Jalili-Nik M, Soukhtanloo M, Ghorbani A, Sadeghnia HR, Mollazadeh H, et al. Auraptene-induced cytotoxicity mechanisms in human malignant glioblastoma (U87) cells: role of reactive oxygen species (ROS). EXCLI J. 2019;18:576-590.DOI: 10.17179/excli2019-1136.

Sahebkar A, Iranshahi M. Biological activities of essential oils from the genus Ferula (Apiaceae). Asian Biomed. 2010;4(6):835-847.DOI: 10.2478/abm-2010-0110.

Gudarzi H, Salimi M, Irian S, Amanzadeh A, Mostafapour Kandelous H, Azadmanesh K, et al. Ethanolic extract of Ferula gummosa is cytotoxic against cancer cells by inducing apoptosis and cell cycle arrest. Nat Prod res. 2015;29(6):546-550. DOI: 10.1080/14786419.2014.951854.

Gharaei R, Akrami H, Heidari S, Asadi MH, Jalili A. The suppression effect of Ferula gummosa Boiss. extracts on cell proliferation through apoptosis induction in gastric cancer cell line Eur J Integr Med. 2013;5(3):241-247.DOI: 10.1016/j.eujim.2013.01.002.

Moradzadeh M, Sadeghnia HR, Mousavi SH, Mahmoodi M, Hosseini A. Ferula gummosa gum induces apoptosis via ROS mechanism in human leukemic cells. Cell Mol Biol (Noisy-le-grand). 2017;63(11):17-22.

DOI: 10.14715/cmb/2017.63.11.4.

Gharaei R, Ghobadi S, Akrami H. Study of apoptosis inducing effects of ethanol extract of Ferula gummosa leaf. Clin Biochem. 2011;44(13):S332.DOI: 10.1016/j.clinbiochem.2011.08.819.

Valdes-Rives SA, Casique-Aguirre D, German-Castelan L, Velasco-Velazquez MA, Gonzalez-Arenas A. apoptotic signaling pathways in glioblastoma and therapeutic implications. Biomed Res Int. 2017;2017:7403747,1-12. DOI: 10.1155/2017/7403747.

Sadeghnia HR, Jamshidi R, Afshari AR, Mollazadeh H, Forouzanfar F, Rakhshandeh H. Terminalia chebula attenuates quinolinate-induced oxidative PC12 and OLN-93 cell death. Mult Scler Relat Disord. 2017;14:60-67.DOI: 10.1016/j.msard.2017.03.012.

Afshari AR, Karimi Roshan M, Soukhtanloo M, Ghorbani A, Rahmani F, Jalili-Nik M, et al. Cytotoxic effects of auraptene against a human malignant glioblastoma cell line. Avicenna J Phytomed. 2019;9(4):334-346.PMID: 31309072.

Poonaki E, Ariakia F, Jalili-Nik M, Shafiee Ardestani M, Tondro G, Samini F, et al. Targeting BMI-1 with PLGA-PEG nanoparticle-containing PTC209 modulates the behavior of human glioblastoma stem cells and cancer cells. Cancer Nanotechnol. 2021;12:5,1-20.DOI: 10.1186/s12645-021-00078-8.

Boussiotis VA, Charest A. Immunotherapies for malignant glioma. Oncogene. 2018;37(9):1121-1141.DOI: 10.1038/s41388-017-0024-z.

Sathornsumetee S, Reardon DA, Desjardins A, Quinn JA, Vredenburgh JJ, Rich JN. Molecularly targeted therapy for malignant glioma. Cancer. 2007;110(1):13-24. DOI: 10.1002/cncr.22741.

Hajimehdipoor H, Esmaeili S, Ramezani R, Jafari Anaraki M, Mosaddegh M. The cytotoxic effects of Ferula persica var. persica and Ferula hezarlalehzarica against HepG2, A549, HT29, MCF7 and MDBK cell lines. Iran J Pharm Sci. 2012;8(2):115-119.

Sadraei H, Asghari GR, Hajhashemi V, Kolagar A, Ebrahimi M. Spasmolytic activity of essential oil and various extracts of Ferula gummosa Boiss. on ileum contractions. Phytomedicine. 2001;8(5):370-376.DOI: 10.1078/0944-7113-00052.

Eslami Jadidi B, Dehpouri A, Nemati F, Rezaei B. Cytotoxicity effects of the Ferula gummosa extract on the cancer cell line Mcf7. J Anim Biol. 2013;5: 4,1-7.

Forouzmand SH, Mousavi SH, Vazifedan V, Nourbakhsh M, Chamani J, Hoseini A, et al. Synergistic effects of Ferula gummosa and radiotherapy on induction of cytotoxicity in HeLa cell line. Avicenna J Phytomed. 2018;8(5):439-477.PMID: 30345231.

Ivanova D, Zhelev Z, Aoki I, Bakalova R, Higashi T. Overproduction of reactive oxygen species - obligatory or not for induction of apoptosis by anticancer drugs. Chin J Cancer Res. 2016;28(4):383-396. DOI: 10.21147/j.issn.1000-9604.2016.04.01.

Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov. 2009;8(7):579-591.DOI: 10.1038/nrd2803.

Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, et al. ROS in cancer therapy: the bright side of the moon. Exp Mol Med. 2020;52(2):192-203. DOI: 10.1038/s12276-020-0384-2.

Sharma A, Kaur M, Katnoria JK, Nagpal AK. Polyphenols in food: cancer prevention and apoptosis induction. Curr Med Chem. 2018;25(36):4740-4757.DOI: 10.2174/0929867324666171006144208.

Piperigkou Z, Manou D, Karamanou K, Theocharis AD. Strategies to target matrix metalloproteinases as therapeutic approach in cancer. Methods Mol Biol; 2018;1731:325-348. DOI: 10.1007/978-1-4939-7595-2_27.

Massague J. G1 cell-cycle control and cancer. Nature. 2004;432(7015):298-306. DOI: 10.1038/nature03094.

Asemani Y, Azadmehr A, Hajiaghaee R, Amirghofran Z. Anticancer potential of Ferula hezarlalehzarica Y. Ajani fraction in Raji lymphoma cell line: induction of apoptosis, cell cycle arrest, and changes in mitochondrial membrane potential. Daru. 2018;26(2):143-154. DOI: 10.1007/s40199-018-0219-z.

Kaufmann SH, Earnshaw WC. Induction of apoptosis by cancer chemotherapy. Exp Cell Res. 2000;256(1):42-49. DOI: 10.1006/excr.2000.4838.

Harris BRE, Wang D, Zhang Y, Ferrari M, Okon A, Cleary MP, et al. Induction of the p53 tumor tuppressor in cancer cells through inhibition of cap-dependent translation. Mol Cell Biol. 2018;38(10):e00367-17,1-39. DOI: 10.1128/MCB.00367-17.

Da Costa DCF, Fialho E, Silva JL. Cancer chemoprevention by resveratrol: the p53 tumor suppressor protein as a promising molecular target. Molecules. 2017;22(6):1014,1-24. DOI: 10.3390/molecules22061014.

Naumann U, Wolburg SKH, Wick W, Rascher G, Schulz JB, et al. Chimeric tumor suppressor 1, a p53-derived chimeric tumor suppressor gene, kills p53 mutant and p53 wild-type glioma cells in synergy with irradiation and CD95 ligand. Cancer Res. 2001;61(15):5833-5842.PMID: 11479223


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