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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Galbanic Acid Improves Accumulation and Toxicity of Arsenic Trioxide in MT-2 Cells

Author(s): Maryam Mahdifar, Fatemeh B. Rassouli*, Mehrdad Iranshahi, Sajad Goudarzi, Marzieh Golizadeh and Houshang Rafatpanah*

Volume 23, Issue 6, 2023

Published on: 13 September, 2022

Page: [699 - 708] Pages: 10

DOI: 10.2174/1871520622666220722105802

Price: $65

Abstract

Background: Galbanic acid (GBA) is a sesquiterpene coumarin with valuable pharmacological effects. Adult T-cell lymphoma (ATL) is an aggressive lymphoid malignancy with a low survival rate. Although arsenic trioxide (ATO) is a standard therapeutic agent for ATL treatment, the efficacy of chemotherapy is limited due to the chemoresistance of cells.

Objective: The present study was carried out to investigate whether GBA in combination with ATO would improve cytotoxicity against ATL cells.

Methods: GBA was isolated from the roots of Ferula szowitsiana by column chromatography on silica gel. MT-2 cells were treated with 20 μM GBA + 4 μM ATO, and viability was evaluated by alamarBlue assay. The cell cycle was analyzed by PI staining, while the activity of P-glycoprotein (P-gp) was evaluated by mitoxantrone efflux assay. To understand the molecular mechanisms of GBA effects, the expression of NF-κB (RelA), P53, CDK4, c-MYC, c-FLIPL, and c-FLIPS was evaluated using real-time PCR.

Results: Combinatorial use of GBA + ATO significantly reduced the viability of MT-2 cells and induced cell cycle arrest in the sub-G1 phase. GBA improved mitoxantrone accumulation in cells, indicating that this agent has inhibitory effects on the functionality of the P-gp efflux pump. Moreover, real-time PCR analysis revealed that GBA + ATO negatively regulated the expression of P53, CDK4, c-FLIPL, and c-FLIPS.

Conclusion: Due to the interesting effects of GBA on the accumulation and toxicity of ATO, combinatorial use of these agents could be considered a new therapeutic approach for ATL treatment.

Keywords: Galbanic acid, adult T cell leukemia, arsenic trioxide, drug accumulation, combination treatment, improved cytotoxicity.

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[1]
Hermine, O.; Ramos, J.C.; Tobinai, K. A review of new findings in adult T-celllLeukemia-lymphoma: A focus on current and emerging treatment strategies. Adv. Ther., 2018, 35(2), 135-152.
[http://dx.doi.org/10.1007/s12325-018-0658-4] [PMID: 29411267]
[2]
Nagasaka, M.; Yamagishi, M.; Yagishita, N.; Araya, N.; Kobayashi, S.; Makiyama, J.; Kubokawa, M.; Yamauchi, J.; Hasegawa, D.; Coler-Reilly, A.L.G.; Tsutsumi, S.; Uemura, Y.; Arai, A.; Takata, A.; Inoue, E.; Hasegawa, Y.; Watanabe, T.; Suzuki, Y.; Uchimaru, K.; Sato, T.; Yamano, Y. Mortality and risk of progression to adult T cell leukemia/lymphoma in HTLV-1-associated myelopathy/tropical spastic paraparesis. Proc. Natl. Acad. Sci. USA, 2020, 117(21), 11685-11691.
[http://dx.doi.org/10.1073/pnas.1920346117] [PMID: 32393644]
[3]
Cherian, M.A.; Baydoun, H.H.; Al-Saleem, J.; Shkriabai, N.; Kvaratskhelia, M.; Green, P.; Ratner, L. Akt pathway activation by human T-cell leukemia virus type 1 Tax oncoprotein. J. Biol. Chem., 2015, 290(43), 26270-26281.
[http://dx.doi.org/10.1074/jbc.M115.684746] [PMID: 26324707]
[4]
Duyao, M.P.; Kessler, D.J.; Spicer, D.B.; Bartholomew, C.; Cleveland, J.L.; Siekevitz, M.; Sonenshein, G.E. Transactivation of the c-myc promoter by human T cell leukemia virus type 1 tax is mediated by NF kappa B. J. Biol. Chem., 1992, 267(23), 16288-16291.
[http://dx.doi.org/10.1016/S0021-9258(18)41998-9] [PMID: 1644814]
[5]
Krueger, A.; Fas, S.C.; Giaisi, M.; Bleumink, M.; Merling, A.; Stumpf, C.; Baumann, S.; Holtkotte, D.; Bosch, V.; Krammer, P.H.; Li-Weber, M. HTLV-1 Tax protects against CD95-mediated apoptosis by induction of the cellular FLICE-inhibitory protein (c-FLIP). Blood, 2006, 107(10), 3933-3939.
[http://dx.doi.org/10.1182/blood-2005-06-2567] [PMID: 16403915]
[6]
Harhaj, E.W. Giam, C.Z. NF-κB signaling mechanisms in HTLV-1-induced adult T-cell leukemia/lymphoma. FEBS J., 2018, 285(18), 3324-3336.
[http://dx.doi.org/10.1111/febs.14492] [PMID: 29722927]
[7]
Suzuki, T.; Kitao, S.; Matsushime, H.; Yoshida, M. HTLV-1 Tax protein interacts with cyclin-dependent kinase inhibitor p16INK4A and counteracts its inhibitory activity towards CDK4. EMBO J., 1996, 15(7), 1607-1614.
[http://dx.doi.org/10.1002/j.1460-2075.1996.tb00505.x] [PMID: 8612584]
[8]
Abeloff, M.D. Abeloff’s Clinical Oncology E-Book; Elsevier Health Sciences: Amsterdam, 2008.
[9]
Ishitsuka, K.; Tamura, K. Human T-cell leukaemia virus type I and adult T-cell leukaemia-lymphoma. Lancet Oncol., 2014, 15(11), e517-e526.
[http://dx.doi.org/10.1016/S1470-2045(14)70202-5] [PMID: 25281470]
[10]
Kchour, G.; Rezaee, R.; Farid, R.; Ghantous, A.; Rafatpanah, H.; Tarhini, M.; Kooshyar, M.M.; El Hajj, H.; Berry, F.; Mortada, M.; Nasser, R.; Shirdel, A.; Dassouki, Z.; Ezzedine, M.; Rahimi, H.; Ghavamzadeh, A.; de Thé, H.; Hermine, O.; Mahmoudi, M.; Bazarbachi, A. The combination of arsenic, interferon-alpha, and zidovudine restores an “immunocompetent-like” cytokine expression profile in patients with adult T-cell leukemia lymphoma. Retrovirology, 2013, 10(1), 91.
[http://dx.doi.org/10.1186/1742-4690-10-91] [PMID: 23962110]
[11]
Lengfelder, E.; Hofmann, W.K.; Nowak, D. Impact of arsenic trioxide in the treatment of acute promyelocytic leukemia. Leukemia, 2012, 26(3), 433-442.
[http://dx.doi.org/10.1038/leu.2011.245] [PMID: 21904379]
[12]
Wang, Q.Q.; Jiang, Y.; Naranmandura, H. Therapeutic strategy of arsenic trioxide in the fight against cancers and other diseases. Metallomics, 2020, 12(3), 326-336.
[http://dx.doi.org/10.1039/c9mt00308h] [PMID: 32163072]
[13]
Ishitsuka, K.; Ikeda, R.; Utsunomiya, A.; Uozumi, K.; Hanada, S.; Suzuki, S.; Takeuchi, S.; Takatsuka, Y.; Takeshita, T.; Ohno, N.; Arima, T. Arsenic trioxide induces apoptosis in HTLV-I infected T-cell lines and fresh adult T-cell leukemia cells through CD95 or tumor necrosis factor alpha receptor independent caspase activation. Leuk. Lymphoma, 2002, 43(5), 1107-1114.
[http://dx.doi.org/10.1080/10428190290021461] [PMID: 12148893]
[14]
Mahieux, R.; Pise-Masison, C.; Gessain, A.; Brady, J.N.; Olivier, R.; Perret, E.; Misteli, T.; Nicot, C. Arsenic trioxide induces apoptosis in human T-cell leukemia virus type 1- and type 2-infected cells by a caspase-3-dependent mechanism involving Bcl-2 cleavage. Blood, 2001, 98(13), 3762-3769.
[http://dx.doi.org/10.1182/blood.V98.13.3762] [PMID: 11739184]
[15]
Bazarbachi, A.; El-Sabban, M.E.; Nasr, R.; Quignon, F.; Awaraji, C.; Kersual, J.; Dianoux, L.; Zermati, Y.; Haidar, J.H.; Hermine, O.; de Thé, H. Arsenic trioxide and interferon-alpha synergize to induce cell cycle arrest and apoptosis in human T-cell lymphotropic virus type I-transformed cells. Blood, 1999, 93(1), 278-283.
[http://dx.doi.org/10.1182/blood.V93.1.278] [PMID: 9864171]
[16]
El-Sabban, M.E.; Nasr, R.; Dbaibo, G.; Hermine, O.; Abboushi, N.; Quignon, F.; Ameisen, J.C.; Bex, F.; de Thé, H.; Bazarbachi, A. Arsenic-interferon-alpha-triggered apoptosis in HTLV-I transformed cells is associated with tax down-regulation and reversal of NF-kappa B activation. Blood, 2000, 96(8), 2849-2855.
[PMID: 11023521]
[17]
Iranshahi, M.; Rezaee, R.; Najaf Najafi, M.; Haghbin, A.; Kasaian, J. Cytotoxic activity of the genus Ferula (Apiaceae) and its bioactive constituents. Avicenna J. Phytomed., 2018, 8(4), 296-312.
[PMID: 30377589]
[18]
Abd El-Razek, M.H.; Ohta, S.; Ahmed, A.A.; Hirata, T. Sesquiterpene coumarins from the roots of Ferula assa-foetida. Phytochemistry, 2001, 58(8), 1289-1295.
[http://dx.doi.org/10.1016/S0031-9422(01)00324-7] [PMID: 11738424]
[19]
Iranshahi, M.; Arfa, P.; Ramezani, M.; Jaafari, M.R.; Sadeghian, H.; Bassarello, C.; Piacente, S.; Pizza, C. Sesquiterpene coumarins from Ferula szowitsiana and in vitro antileishmanial activity of 7-prenyloxycoumarins against promastigotes. Phytochemistry, 2007, 68(4), 554-561.
[http://dx.doi.org/10.1016/j.phytochem.2006.11.002] [PMID: 17196626]
[20]
Iranshahi, M.; Kalategi, F.; Rezaee, R.; Shahverdi, A.R.; Ito, C.; Furukawa, H.; Tokuda, H.; Itoigawa, M. Cancer chemopreventive activity of terpenoid coumarins from Ferula species. Planta Med., 2008, 74(2), 147-150.
[http://dx.doi.org/10.1055/s-2008-1034293] [PMID: 18240102]
[21]
Iranshahy, M.; Iranshahi, M. Traditional uses, phytochemistry and pharmacology of asafoetida (Ferula assa-foetida oleo-gum-resin)-A review. J. Ethnopharmacol., 2011, 134(1), 1-10.
[http://dx.doi.org/10.1016/j.jep.2010.11.067] [PMID: 21130854]
[22]
Kasaian, J.; Iranshahy, M.; Iranshahi, M. Synthesis, biosynthesis and biological activities of galbanic acid–A review. Pharm. Biol., 2014, 52(4), 524-531.
[http://dx.doi.org/10.3109/13880209.2013.846916] [PMID: 25471377]
[23]
Kim, K.H.; Lee, H.J.; Jeong, S.J.; Lee, H.J.; Lee, E.O.; Kim, H.S.; Zhang, Y.; Ryu, S.Y.; Lee, M.H.; Lü, J.; Kim, S.H. Galbanic acid isolated from Ferula assafoetida exerts in vivo anti-tumor activity in association with anti-angiogenesis and anti-proliferation. Pharm. Res., 2011, 28(3), 597-609.
[http://dx.doi.org/10.1007/s11095-010-0311-7] [PMID: 21063754]
[24]
Shahcheraghi, S.H.; Lotfi, M.; Soukhtanloo, M.; Ghayour Mobarhan, M.; Jaliani, H.Z.; Sadeghnia, H.R.; Ghorbani, A. Effects of galbanic acid on proliferation, migration, andaApoptosis of glioblastoma cells through the PI3K/Akt/MTOR signaling pathway. Curr. Mol. Pharmacol., 2021, 14(1), 79-87.
[http://dx.doi.org/10.2174/1874467213666200512075507] [PMID: 32394847]
[25]
Hashemi, R. In vitro study of radiosensitivity effects of galbanic acid on ovarian tumor cells (OVCAR-3 Cell Line). Nat. Prod. Commun. 2021, 16(10), 1934578X211046068.
[26]
Hanafi-Bojd, M.Y.; Iranshahi, M.; Mosaffa, F.; Tehrani, S.O.; Kalalinia, F.; Behravan, J. Farnesiferol A from Ferula persica and galbanic acid from Ferula szowitsiana inhibit P-glycoprotein-mediated rhodamine efflux in breast cancer cell lines. Planta Med., 2011, 77(14), 1590-1593.
[http://dx.doi.org/10.1055/s-0030-1270987] [PMID: 21484672]
[27]
Kchour, G.; Tarhini, M.; Kooshyar, M.M.; El Hajj, H.; Wattel, E.; Mahmoudi, M.; Hatoum, H.; Rahimi, H.; Maleki, M.; Rafatpanah, H.; Rezaee, S.A.; Yazdi, M.T.; Shirdel, A.; de Thé, H.; Hermine, O.; Farid, R.; Bazarbachi, A. Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL). Blood, 2009, 113(26), 6528-6532.
[http://dx.doi.org/10.1182/blood-2009-03-211821] [PMID: 19411628]
[28]
Eskandani, M.; Abdolalizadeh, J.; Hamishehkar, H.; Nazemiyeh, H.; Barar, J. Galbanic acid inhibits HIF-1α expression via EGFR/HIF-1α pathway in cancer cells. Fitoterapia, 2015, 101, 1-11.
[http://dx.doi.org/10.1016/j.fitote.2014.12.003] [PMID: 25510323]
[29]
Eskandani, M.; Barar, J.; Dolatabadi, J.E.; Hamishehkar, H.; Nazemiyeh, H. Formulation, characterization, and geno/cytotoxicity studies of galbanic acid-loaded solid lipid nanoparticles. Pharm. Biol., 2015, 53(10), 1525-1538.
[http://dx.doi.org/10.3109/13880209.2014.991836] [PMID: 25853953]
[30]
Jafari, A.; Teymouri, M.; Ebrahimi Nik, M.; Abbasi, A.; Iranshahi, M.; Hanafi-Bojd, M.Y.; Jafari, M.R. Interactive anticancer effect of nanomicellar curcumin and galbanic acid combination therapy with some common chemotherapeutics in colon carcinoma cells. Avicenna J. Phytomed., 2019, 9(3), 237-247.
[PMID: 31143691]
[31]
Kim, Y.H.; Shin, E.A.; Jung, J.H.; Park, J.E.; Koo, J.; Koo, J.I.; Shim, B.S.; Kim, S.H. Galbanic acid potentiates TRAIL induced apoptosis in resistant non-small cell lung cancer cells via inhibition of MDR1 and activation of caspases and DR5. Eur. J. Pharmacol., 2019, 847, 91-96.
[http://dx.doi.org/10.1016/j.ejphar.2019.01.028] [PMID: 30689998]
[32]
Zhang, Y.; Kim, K.H.; Zhang, W.; Guo, Y.; Kim, S.H.; Lü, J. Galbanic acid decreases androgen receptor abundance and signaling and induces G1 arrest in prostate cancer cells. Int. J. Cancer, 2012, 130(1), 200-212.
[http://dx.doi.org/10.1002/ijc.25993] [PMID: 21328348]
[33]
Oh, B.S.; Shin, E.A.; Jung, J.H.; Jung, D.B.; Kim, B.; Shim, B.S.; Yazdi, M.C.; Iranshahi, M.; Kim, S.H. Apoptotic effect of galbanic acid via activation of caspases and inhibition of Mcl-1 in H460 non-small lung carcinoma cells. Phytother. Res., 2015, 29(6), 844-849.
[http://dx.doi.org/10.1002/ptr.5320] [PMID: 25753585]
[34]
Kazemi, M.; Kouhpeikar, H.; Delbari, Z.; Khodadadi, F.; Gerayli, S.; Iranshahi, M.; Mosavat, A.; Behnam Rassouli, F.; Rafatpanah, H. Combination of auraptene and arsenic trioxide induces apoptosis and cellular accumulation in the subG1 phase in adult T-cell leukemia cells. Iran. J. Basic Med. Sci., 2021, 24(12), 1643-1649.
[PMID: 35432798]
[35]
Delbari, Z. Combination of umbelliprenin and arsenic trioxide acts as an effective modality against T-cell leukemia/lymphoma cells. Nat. Prod. Commun. 2022, 17(1), 1934578X211072334.
[36]
Kouhpaikar, H.; Sadeghian, M.H.; Rafatpanah, H.; Kazemi, M.; Iranshahi, M.; Delbari, Z.; Khodadadi, F.; Ayatollahi, H.; Rassouli, F.B. Synergy between parthenolide and arsenic trioxide in adult T-cell leukemia/lymphoma cells in vitro. Iran. J. Basic Med. Sci., 2020, 23(5), 616-622.
[PMID: 32742599]
[37]
Lau, A.; Nightingale, S.; Taylor, G.P.; Gant, T.W.; Cann, A.J. Enhanced MDR1 gene expression in human T-cell leukemia virus-I-infected patients offers new prospects for therapy. Blood, 1998, 91(7), 2467-2474.
[http://dx.doi.org/10.1182/blood.V91.7.2467] [PMID: 9516147]
[38]
Ariumi, Y.; Kaida, A.; Lin, J.Y.; Hirota, M.; Masui, O.; Yamaoka, S.; Taya, Y.; Shimotohno, K. HTLV-1 tax oncoprotein represses the p53-mediated trans-activation function through coactivator CBP sequestration. Oncogene, 2000, 19(12), 1491-1499.
[http://dx.doi.org/10.1038/sj.onc.1203450] [PMID: 10734308]
[39]
Haller, K.; Ruckes, T.; Schmitt, I.; Saul, D.; Derow, E.; Grassmann, R. Tax-dependent stimulation of G1 phase-specific cyclin-dependent kinases and increased expression of signal transduction genes characterize HTLV type 1-transformed T cells. AIDS Res. Hum. Retroviruses, 2000, 16(16), 1683-1688.
[http://dx.doi.org/10.1089/08892220050193146] [PMID: 11080810]
[40]
Mori, N.; Fujii, M.; Ikeda, S.; Yamada, Y.; Tomonaga, M.; Ballard, D.W.; Yamamoto, N. Constitutive activation of NF-kappaB in primary adult T-cell leukemia cells. Blood, 1999, 93(7), 2360-2368.
[PMID: 10090947]
[41]
Sun, S.C.; Yamaoka, S. Activation of NF-kappaB by HTLV-I and implications for cell transformation. Oncogene, 2005, 24(39), 5952-5964.
[http://dx.doi.org/10.1038/sj.onc.1208969] [PMID: 16155602]
[42]
Yoshida, M. Multiple viral strategies of HTLV-1 for dysregulation of cell growth control. Annu. Rev. Immunol., 2001, 19(1), 475-496.
[http://dx.doi.org/10.1146/annurev.immunol.19.1.475] [PMID: 11244044]
[43]
Kashanchi, F.; Brady, J.N. Transcriptional and post-transcriptional gene regulation of HTLV-1. Oncogene, 2005, 24(39), 5938-5951.
[http://dx.doi.org/10.1038/sj.onc.1208973] [PMID: 16155601]
[44]
Matsuoka, M.; Jeang, K-T. Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation. Nat. Rev. Cancer, 2007, 7(4), 270-280.
[http://dx.doi.org/10.1038/nrc2111] [PMID: 17384582]
[45]
Sherr, C.J.; Roberts, J.M. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev., 1995, 9(10), 1149-1163.
[http://dx.doi.org/10.1101/gad.9.10.1149] [PMID: 7758941]
[46]
Djerbi, M.; Screpanti, V.; Catrina, A.I.; Bogen, B.; Biberfeld, P.; Grandien, A. The inhibitor of death receptor signaling, FLICE-inhibitory protein defines a new class of tumor progression factors. J. Exp. Med., 1999, 190(7), 1025-1032.
[http://dx.doi.org/10.1084/jem.190.7.1025] [PMID: 10510092]
[47]
Medema, J.P.; de Jong, J.; van Hall, T.; Melief, C.J.; Offringa, R. Immune escape of tumors in vivo by expression of cellular FLICE-inhibitory protein. J. Exp. Med., 1999, 190(7), 1033-1038.
[http://dx.doi.org/10.1084/jem.190.7.1033] [PMID: 10510093]
[48]
Okamoto, K.; Fujisawa, J.; Reth, M.; Yonehara, S. Human T-cell leukemia virus type-I oncoprotein Tax inhibits Fas-mediated apoptosis by inducing cellular FLIP through activation of NF-kappaB. Genes Cells, 2006, 11(2), 177-191.
[http://dx.doi.org/10.1111/j.1365-2443.2006.00927.x] [PMID: 16436054]
[49]
Ozaki, T.; Nakagawara, A. p53: The attractive tumor suppressor in the cancer research field. J. Biomed. Biotechnol., 2011, 2011, 603925.
[http://dx.doi.org/10.1155/2011/603925] [PMID: 21188172]
[50]
Xu-Monette, Z.Y.; Medeiros, L.J.; Li, Y.; Orlowski, R.Z.; Andreeff, M.; Bueso-Ramos, C.E.; Greiner, T.C.; McDonnell, T.J.; Young, K.H. Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies. Blood, 2012, 119(16), 3668-3683.
[http://dx.doi.org/10.1182/blood-2011-11-366062] [PMID: 22275381]
[51]
Bartke, T.; Siegmund, D.; Peters, N.; Reichwein, M.; Henkler, F.; Scheurich, P.; Wajant, H. p53 upregulates cFLIP, inhibits transcription of NF-kappaB-regulated genes and induces caspase-8-independent cell death in DLD-1 cells. Oncogene, 2001, 20(5), 571-580.
[http://dx.doi.org/10.1038/sj.onc.1204124] [PMID: 11313989]

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