Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

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

General Research Article

Erianin as a Promising Novel Agent in the Treatment of Neuroblastoma: The Anticancer Effects and Underlying Molecular Mechanisms

Author(s): Sema Serter Kocoglu*, Mücahit Seçme and Fatma Bahar Sunay

Volume 23, Issue 10, 2023

Published on: 15 March, 2023

Page: [1204 - 1210] Pages: 7

DOI: 10.2174/1871520623666230228095429

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Erianin is an active dibenzyl compound isolated from Dendrobium officinale and Dendrobium chrysotoxum and there are very few studies on molecular mechanisms and drug targets of erianin. In addition, there is no study investigating the anti-cancer effect of erianin on neuroblastoma cells.

Objective: The aim of the study is to investigate the anticancer effect of erianin and the underlying mechanism of this effect on SH-SY5Y cells.

Methods: The effects of erianin on cell viability, invasion and migration were determined by XTT, matrigel chamber and wound healing evaluation, respectively. Expression changes of miRNAs (microRNA) and apoptosis-related genes were evaluated by RT-PCR, and the apoptosis rate was supported by Annexin V evaluation.

Results: Erianin significantly decreased cell proliferation, invasion and migration. Erianin administration caused apoptosis by significantly increasing caspase-7, FADD (Fas-associated protein with death domain), BID (BH3 Interacting Domain Death Agonist) and DR5 (Death receptor 5) gene expressions. While the rate of total apoptotic cells was 45.35 ± 6.80% in SH-SY5Y cells treated with erianin, it was 0.133 ± 0.05% in the control group (p = 0.000). In addition, erianin administration significantly decreased the expressions of hsa-miR-155-5p (p = 0.014) and hsa-miR-223-3p (p = 0.004). Also, our study demonstrated for the first time the relationship between erianin and mi-RNAs in a cancer cell.

Conclusion: Our study suggests that erianin may be a natural, safe and easily accessible drug candidate that can be used in the treatment of neuroblastoma.

Keywords: Neuroblastoma, erianin, apoptosis, miRNAs, anticancer, cell viability, invasion, migration.

Graphical Abstract
[1]
Laut, A.K.; Dorneburg, C.; Fürstberger, A.; Barth, T.F.E.; Kestler, H.A.; Debatin, K.M.; Beltinger, C. CHD5 inhibits metastasis of neuroblastoma. Oncogene, 2022, 41(5), 622-633.
[http://dx.doi.org/10.1038/s41388-021-02081-0] [PMID: 34789839]
[2]
Stainczyk, S.A.; Westermann, F. Neuroblastoma-telomere maintenance, deregulated signaling transduction and beyond. Int. J. Cancer, 2022, 150(6), 903-915.
[http://dx.doi.org/10.1002/ijc.33839] [PMID: 34636058]
[3]
Mahapatra, S.; Challagundla, K.B. Neuroblastoma; StatPearls: Treasure Island, 2022.
[4]
Yang, H.; Guo, J.F.; Zhang, M.L.; Li, A.M. LncRNA SNHG4 promotes neuroblastoma proliferation, migration, and invasion by sponging miR-377-3p. Neoplasma, 2020, 67(5), 1054-1062.
[http://dx.doi.org/10.4149/neo_2020_191023N1081] [PMID: 32614236]
[5]
Sahin, B.; Gunes, H.; Ozturk, A. Investigation of the mechanisms involved in anticancer effect of glucosamine sulfate on SH-SY5Y cell line. Bratisl. Med. J., 2022, 123(5), 366-371.
[http://dx.doi.org/10.4149/BLL_2022_058] [PMID: 35420883]
[6]
Board, P.P.T.E. Neuroblastoma Treatment (PDQ®); PDQ, 2022, pp. 1-81.
[7]
Kocoglu, S.S.; Seçme, M.; Elmas, L. Erianin, a promising agent in the treatment of glioblastoma multiforme triggers apoptosis in U373 and A172 glioblastoma cells. Archieves of Biological Sciences, 2022, 74(3), 227-234.
[8]
Xu, Y.; Fang, R.; Shao, J.; Cai, Z. Erianin induces triple-negative breast cancer cells apoptosis by activating PI3K/Akt pathway. Biosci. Rep., 2021, 41(6), BSR20210093.
[http://dx.doi.org/10.1042/BSR20210093] [PMID: 34036307]
[9]
Wang, Y.; Chu, F.; Lin, J.; Li, Y.; Johnson, N.; Zhang, J.; Gai, C.; Su, Z.; Cheng, H.; Wang, L.; Ding, X. Erianin, the main active ingredient of Dendrobium chrysotoxum Lindl, inhibits precancerous lesions of gastric cancer (PLGC) through suppression of the HRAS-PI3K-AKT signaling pathway as revealed by network pharmacology and in vitro experimental verification. J. Ethnopharmacol., 2021, 279, 114399.
[http://dx.doi.org/10.1016/j.jep.2021.114399] [PMID: 34246740]
[10]
Zhu, Q.; Sheng, Y.; Li, W.; Wang, J.; Ma, Y.; Du, B.; Tang, Y. Erianin, a novel dibenzyl compound in Dendrobium extract, inhibits bladder cancer cell growth via the mitochondrial apoptosis and JNK pathways. Toxicol. Appl. Pharmacol., 2019, 371, 41-54.
[http://dx.doi.org/10.1016/j.taap.2019.03.027] [PMID: 30946863]
[11]
Sun, J.; Fu, X.; Wang, Y.; Liu, Y.; Zhang, Y.; Hao, T.; Hu, X. Erianin inhibits the proliferation of T47D cells by inhibiting cell cycles, inducing apoptosis and suppressing migration. Am. J. Transl. Res., 2016, 8(7), 3077-3086.
[PMID: 27508028]
[12]
Wang, H.; Zhang, T.; Sun, W.; Wang, Z.; Zuo, D.; Zhou, Z.; Li, S.; Xu, J.; Yin, F.; Hua, Y.; Cai, Z. Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo. Cell Death Dis., 2016, 7(6), e2247.
[http://dx.doi.org/10.1038/cddis.2016.138] [PMID: 27253411]
[13]
Chen, P.; Wu, Q.; Feng, J.; Yan, L.; Sun, Y.; Liu, S.; Xiang, Y.; Zhang, M.; Pan, T.; Chen, X.; Duan, T.; Zhai, L.; Zhai, B.; Wang, W.; Zhang, R.; Chen, B.; Han, X.; Li, Y.; Chen, L.; Liu, Y.; Huang, X.; Jin, T.; Zhang, W.; Luo, H.; Chen, X.; Li, Y.; Li, Q.; Li, G.; Zhang, Q.; Zhuo, L.; Yang, Z.; Tang, H.; Xie, T.; Ouyang, X.; Sui, X. Erianin, a novel dibenzyl compound in Dendrobium extract, inhibits lung cancer cell growth and migration via calcium/calmodulin-dependent ferroptosis. Signal Transduct. Target. Ther., 2020, 5(1), 51.
[http://dx.doi.org/10.1038/s41392-020-0149-3] [PMID: 32382060]
[14]
Zhang, X.; Wang, Y.; Li, X.; Yang, A.; Li, Z.; Wang, D. The anti-carcinogenesis properties of erianin in the modulation of oxidative stress-mediated apoptosis and immune response in liver cancer. Aging, 2019, 11(22), 10284-10300.
[http://dx.doi.org/10.18632/aging.102456] [PMID: 31754081]
[15]
Elmore, S. Apoptosis: A review of programmed cell death. Toxicol. Pathol., 2007, 35(4), 495-516.
[http://dx.doi.org/10.1080/01926230701320337] [PMID: 17562483]
[16]
Boice, A.; Bouchier-Hayes, L. Targeting apoptotic caspases in cancer. Biochim. Biophys. Acta Mol. Cell Res., 2020, 1867(6), 118688.
[http://dx.doi.org/10.1016/j.bbamcr.2020.118688] [PMID: 32087180]
[17]
Scorrano, L.; Ashiya, M.; Buttle, K.; Weiler, S.; Oakes, S.A.; Mannella, C.A.; Korsmeyer, S.J. A distinct pathway remodels mitochondrial cristae and mobilizes cytochrome C during apoptosis. Dev. Cell, 2002, 2(1), 55-67.
[http://dx.doi.org/10.1016/S1534-5807(01)00116-2] [PMID: 11782314]
[18]
Slee, E.A.; Harte, M.T.; Kluck, R.M.; Wolf, B.B.; Casiano, C.A.; Newmeyer, D.D.; Wang, H.G.; Reed, J.C.; Nicholson, D.W.; Alnemri, E.S.; Green, D.R.; Martin, S.J. Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J. Cell Biol., 1999, 144(2), 281-292.
[http://dx.doi.org/10.1083/jcb.144.2.281] [PMID: 9922454]
[19]
Walsh, J.G.; Cullen, S.P.; Sheridan, C.; Lüthi, A.U.; Gerner, C.; Martin, S.J. Executioner caspase-3 and caspase-7 are functionally distinct proteases. Proc. Natl. Acad. Sci. USA, 2008, 105(35), 12815-12819.
[http://dx.doi.org/10.1073/pnas.0707715105] [PMID: 18723680]
[20]
Brentnall, M.; Rodriguez-Menocal, L.; De Guevara, R.L.; Cepero, E.; Boise, L.H. Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol., 2013, 14(1), 32.
[http://dx.doi.org/10.1186/1471-2121-14-32] [PMID: 23834359]
[21]
Oh, Y.T.; Sun, S.Y. Regulation of cancer metastasis by trail/death receptor signaling. Biomolecules, 2021, 11(4), 499.
[http://dx.doi.org/10.3390/biom11040499] [PMID: 33810241]
[22]
Liu, Y.T.; Hsieh, M.J.; Lin, J.T.; Chen, G.; Lin, C.C.; Lo, Y.S.; Chuang, Y.C.; Hsi, Y.T.; Chen, M.K.; Chou, M.C. Erianin induces cell apoptosis through ERK pathway in human nasopharyngeal carcinoma. Biomed. Pharmacother., 2019, 111, 262-269.
[http://dx.doi.org/10.1016/j.biopha.2018.12.081] [PMID: 30590314]
[23]
Pottoo, F.H.; Barkat, M.A. Harshita; Ansari, M.A.; Javed, M.N.; Sajid Jamal, Q.M.; Kamal, M.A. Nanotechnological based miRNA intervention in the therapeutic management of neuroblastoma. Semin. Cancer Biol., 2021, 69, 100-108.
[http://dx.doi.org/10.1016/j.semcancer.2019.09.017] [PMID: 31562954]
[24]
Mohammadi, M.; Goodarzi, M.; Jaafari, M.R.; Mirzaei, H.R.; Mirzaei, H. Circulating microRNA: A new candidate for diagnostic biomarker in neuroblastoma. Cancer Gene Ther., 2016, 23(11), 371-372.
[http://dx.doi.org/10.1038/cgt.2016.45] [PMID: 27740613]
[25]
Bayraktar, R.; Van Roosbroeck, K. miR-155 in cancer drug resistance and as target for miRNA-based therapeutics. Cancer Metastasis Rev., 2018, 37(1), 33-44.
[http://dx.doi.org/10.1007/s10555-017-9724-7] [PMID: 29282605]
[26]
Lv, H.; Guo, J.; Li, S.; Jiang, D. miR-155 inhibitor reduces the proliferation and migration in osteosarcoma MG-63 cells. Exp. Ther. Med., 2014, 8(5), 1575-1580.
[http://dx.doi.org/10.3892/etm.2014.1942] [PMID: 25289062]
[27]
Meng, W.; Jiang, L.; Lu, L.; Hu, H.; Yu, H.; Ding, D.; Xiao, K.; Zheng, W.; Guo, H.; Ma, W. Anti-miR-155 oligonucleotide enhances chemosensitivity of U251 cell to taxol by inducing apoptosis. Cell Biol. Int., 2012, 36(7), 653-659.
[http://dx.doi.org/10.1042/CBI20100918] [PMID: 22276743]
[28]
Feng, M.; Luo, X.; Gu, C.; Fei, J. Seed targeting with tiny anti-miR-155 inhibits malignant progression of multiple myeloma cells. J. Drug Target., 2015, 23(1), 59-66.
[http://dx.doi.org/10.3109/1061186X.2014.951653] [PMID: 25185784]
[29]
Choi, C.H.; Park, Y.A.; Choi, J.J.; Song, T.; Song, S.Y.; Lee, Y.Y.; Lee, J.W.; Kim, T.J.; Kim, B.G.; Bae, D.S. Angiotensin II type I receptor and miR-155 in endometrial cancers: Synergistic antiproliferative effects of anti-miR-155 and losartan on endometrial cancer cells. Gynecol. Oncol., 2012, 126(1), 124-131.
[http://dx.doi.org/10.1016/j.ygyno.2012.04.020] [PMID: 22525818]
[30]
Zhu, Y.; Li, K.; Yan, L.; He, Y.; Wang, L.; Sheng, L. miR-223-3p promotes cell proliferation and invasion by targeting Arid1a in gastric cancer. Acta Biochim. Biophys. Sin., 2020, 52(2), 150-159.
[http://dx.doi.org/10.1093/abbs/gmz151] [PMID: 31912865]
[31]
Han, L.L.; Zhou, X.J.; Li, F.J.; Hao, X.W.; Jiang, Z.; Dong, Q.; Chen, X. MiR-223-3p promotes the growth and invasion of neuroblastoma cell via targeting FOXO1. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(20), 8984-8990.
[PMID: 31696486]
[32]
Xiang, Y.; Chen, X.; Wang, W.; Zhai, L.; Sun, X.; Feng, J.; Duan, T.; Zhang, M.; Pan, T.; Yan, L.; Jin, T.; Gao, Q.; Wen, C.; Ma, W.; Liu, W.; Wang, D.; Wu, Q.; Xie, T.; Sui, X. Natural product erianin inhibits bladder cancer cell growth by inducing ferroptosis via NRF2 inactivation. Front. Pharmacol., 2021, 12, 775506.
[http://dx.doi.org/10.3389/fphar.2021.775506] [PMID: 34776986]
[33]
Li, M.; He, Y.; Peng, C.; Xie, X.; Hu, G. Erianin inhibits human cervical cancer cell through regulation of tumor protein p53 via the extracellular signal regulated kinase signaling pathway. Oncol. Lett., 2018, 16(4), 5006-5012.
[http://dx.doi.org/10.3892/ol.2018.9267] [PMID: 30250566]
[34]
Justus, C.R.; Leffler, N.; Ruiz-Echevarria, M.; Yang, L.V. In vitro cell migration and invasion assays. J. Vis. Exp., 2014, 88(88), 51046.
[http://dx.doi.org/10.3791/51046] [PMID: 24962652]
[35]
Liu, Z.; Huang, L.; Sun, L.; Nie, H.; Liang, Y.; Huang, J.; Wu, F.; Hu, X. Ecust004 suppresses breast cancer cell growth, invasion, and migration via EMT regulation. Drug Des. Devel. Ther., 2021, 15, 3451-3461.
[http://dx.doi.org/10.2147/DDDT.S309132] [PMID: 34408399]
[36]
Yang, L.; Hu, Y.; Zhou, G.; Chen, Q.; Song, Z. Erianin suppresses hepatocellular carcinoma cells through down-regulation of PI3K/AKT, p38 and ERK MAPK signaling pathways. Biosci. Rep., 2020, 40(7), BSR20193137.
[http://dx.doi.org/10.1042/BSR20193137] [PMID: 32677672]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy