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Recent Patents on Anti-Cancer Drug Discovery

Author(s): Elaheh Amini, Mohammad Nabiuni, Seyed Bahram Behzad, Danial Seyfi, Farhad Eisvand, Amirhossein Sahebkar* and Abolfazl Shakeri*

DOI: 10.2174/1574892815666200713162304

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Anticancer Potential of Aguerin B, a Sesquiterpene Lactone Isolated from Centaurea behen in Metastatic Breast Cancer Cells

Page: [165 - 173] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: Breast carcinoma is a malignant disease that represents the most common non-skin malignancy and a chief reason of cancer death in women. Large interest is growing in the use of natural products for cancer treatment, especially with goal of suppression angiogenesis, tumor cell growth, motility, as well as invasion and metastasis with low/no toxicity. It is evident from recent patents on the anticancer properties of sesquiterpene lactones such as parthenolide.

Objective: In this study, using MDA-MB-231 cells of a human breast adenocarcinoma, the effects of aguerin B, as a natural sesquiterpene lactone, has been evaluated, in terms of the expression of metastatic-related genes (Pak-1, Rac-1 and HIF-1α).

Methods: Cytotoxicity of aguerin B was tested toward MDA-MB-231 breast tumor cells using MTT. Scratch assay was accomplished to evaluate the tumor cell invasion. To understand the underlying molecular basis, the mRNA expressions were evaluated by real time PCR.

Results: It was found that aguerin B significantly inhibited human breast cancer cell growth in vitro (IC50 = 2μg/mL) and this effect was accompanied with a persuasive suppression on metastasis. Our results showed that aguerin B in IC50 concentration down-regulated Rac-1, Pak-1, Hif-1α and Zeb-1 transcriptional levels.

Conclusion: Taken together, this study demonstrated that aguerin B possessed potential anti-metastatic effect, suggesting that it may consider as a potential multi target bio compound for treatment of breast metastatic carcinoma.

Keywords: Aguerin B, anticancer, breast metastatic carcinoma, patent, Rac-1, sesquiterpene lactone.

[1]
Craig WJ. Health-promoting properties of common herbs. Am J Clin Nutr 1999; 70: 491s-9s.
[http://dx.doi.org/10.1093/ajcn/70.3.491s]
[2]
Iranshahi M, Sahebkar A, Hosseini ST, Takasaki M, Konoshima T, Tokuda H. Cancer chemopreventive activity of diversin from Ferula diversivittatain vitro and in vivo. Phytomedicine 2010; 17(3-4): 269-73.
[http://dx.doi.org/10.1016/j.phymed.2009.05.020]
[3]
Shakeri A, Sahebkar A. Anti-cancer products from marine sponges: Progress and promise. Recent Pat Drug Deliv Formul 2015; 9: 187-8.
[http://dx.doi.org/10.2174/1872211309666150529131549]
[4]
Wang F, Gao Y, Tang L, et al. A novel PAK4-CEBPB-CLDN4 axis involving in breast cancer cell migration and invasion. Biochem Biophys Res Commun 2019; 511: 404-8.
[http://dx.doi.org/10.1016/j.bbrc.2019.02.070]
[5]
Chaw S, Majeed AA, Dalley A, Chan A, Stein S, Farah C. Epithelial to Mesenchymal Transition (EMT) biomarkers-E-cadherin, beta-catenin, APC and Vimentin-in oral squamous cell carcinogenesis and transformation. Oral Oncol 2012; 48: 997-1006.
[http://dx.doi.org/10.1016/j.oraloncology.2012.05.011]
[6]
Redig AJ, McAllister SS. Breast cancer as a systemic disease: A view of metastasis. J Intern Med 2013; 274(2): 113-26.
[http://dx.doi.org/10.1111/joim.12084]
[7]
Zong A, Zhao T, Zhang Y, et al. Anti-metastatic and anti-angiogenic activities of sulfated polysaccharide of Sepiella maindroni ink. Carbohydr Polym 2013; 91: 403-9.
[http://dx.doi.org/10.1016/j.carbpol.2012.08.050]
[8]
Guerra G. Poletto V, Biggiogera M, et al. Circulating endothelial progenitor cells from patients with renal cell carcinoma display aberrant VEGF regulation, reduced apoptosis and altered ultrastructure. Ital J Anat Embryol 2015; 120: 111.
[9]
Olea-Flores M, Juarez-Cruz JC, Mendoza-Catalan MA, Padilla-Benavides T, Navarro-Tito N. Signaling pathways induced by leptin during epithelial(-)mesenchymal transition in breast cancer. Int J Mol Sci 2018; 19: 3493-512.
[http://dx.doi.org/10.3390/ijms19113493]
[10]
Gilkes DM, Semenza GL. Role of hypoxia-inducible factors in breast cancer metastasis. Future Oncol 2013; 9: 1623-36.
[http://dx.doi.org/10.2217/fon.13.92]
[11]
Giussani M, Merlino G, Cappelletti V, Tagliabue E, Daidone MG. Tumor-extracellular matrix interactions: Identification of tools associated with breast cancer progression. Semin Cancer Biol 2015; 35: 3-10.
[http://dx.doi.org/10.1016/j.semcancer.2015.09.012]
[12]
Forster JC, Harriss-Phillips WM, Douglass MJ, Bezak E. A review of the development of tumor vasculature and its effects on the tumor microenvironment. Hypoxia (Auckl) 2017; 5: 21-32.
[http://dx.doi.org/10.2147/HP.S133231]
[13]
Shakeri A, Ward N, Panahi Y, Sahebkar A. Anti-angiogenic activity of curcumin in cancer therapy: A narrative review. Curr Vasc Pharmacol 2018; 17: 262-8.
[http://dx.doi.org/10.2174/1570161116666180209113014]
[14]
Asadi-Samani M, Kooti W, Aslani E, Shirzad H. A systematic review of Iran’s medicinal plants with anticancer effects. J Evid Based Complementary Altern Med 2016; 21: 143-53.
[http://dx.doi.org/10.1177/2156587215600873]
[15]
Mitra S, Dash R. Natural products for the management and prevention of breast cancer eCAM 2018; 2018: 8324696-718.
[http://dx.doi.org/10.1155/2018/8324696.]
[16]
Chimplee S, Graidist P, Srisawat T, Sukrong S, Bissanum R, Kanokwiroon K. Anti-breast cancer potential of frullanolide from Grangea maderaspatana plant by inducing apoptosis. Oncol Lett 2019; 17: 5283-91.
[http://dx.doi.org/10.3892/ol.2019.10209]
[17]
Ren Y, Yu J, Kinghorn AD. Development of anticancer agents from plant-derived sesquiterpene lactones. Curr Med Chem 2016; 23: 2397-420.
[http://dx.doi.org/10.2174/0929867323666160510123255]
[18]
Shakeri A, Masullo M, Bottone A, et al. Sesquiterpene lactones from Centaurea rhizantha C.A. Meyer. Nat Prod Res 2018; 33: 2016-23.
[http://dx.doi.org/10.1080/14786419.2018.1483926]
[19]
Pérez-Castorena AL, Nieto-Camacho A, Maldonado E. Sesquiterpene lactones and other constituents from Stevia jorullensis. Biochem Syst Ecol 2020; 89: 104003-6.
[http://dx.doi.org/10.1016/j.bse.2020.104003]
[20]
Sabel R, Fronza AS, Carrenho LZB, et al. Anti-inflammatory activity of the sesquiterpene lactone diacethylpiptocarphol in dextransulfate sodium-induced colitis in mice. J Ethnopharmacol 2019; 245: 112186-92.
[http://dx.doi.org/10.1016/j.jep.2019.112186]
[21]
Chadwick M, Trewin H, Gawthrop F, Wagstaff C. Sesquiterpenoids lactones: Benefits to plants and people. Int J Mol Sci 2013; 14: 12780-805.
[http://dx.doi.org/10.3390/ijms140612780]
[22]
Rhodes A. Method for the extraction of sesquiterpene lactones. US5384121, In: 1995.
[23]
Hsieh H-P, Hsu T-A, Hwang D-R. Treatment of hepatitis C virus infection with sesquiterpene lactones. . US20040229936, In: 2004.
[24]
Elsebai MF. Sesquiterpene lactones as potent and broad spectrum antiviral compounds against all genotypes of Hepatitis C Virus (HCV). . WO2016169573, In: 2016.
[25]
Grothe T, Roemer E, Wabnitz P. Use of tricyclic sesquiterpene lactones in the treatment of obesity and related diseases and non-therapeutic treatable conditions US20130023586,. 2013.
[26]
Hwang DH, Fischer NH. Use of sesquiterpene lactones for treatment of severe inflammatory disorders. . US5905089, In: 1999.
[27]
Jean D. Cosmetic or medicinal composition containing sesquiterpene lactone or the like for treating hair-growth related disorders, and preparation method. US20040115289, In: 2004.
[28]
Gobrecht PLA, Fischer D. Parthenolide and its derivative for use in the treatment of axonal damage. US20190388388, In: 2019.
[29]
Myers CE, Trepel J, Sausville E, Samid D, Miller A, Curt G. Monoterpenes, sesquiterpenes and diterpenes as cancer therapy. US5602184 In: 1997.
[30]
Ghantous A, Gali-Muhtasib H, Vuorela H, Saliba NA, Darwiche N. What made sesquiterpene lactones reach cancer clinical trials? Drug Discov Today 2010; 15: 668-78.
[http://dx.doi.org/10.1016/j.drudis.2010.06.002]
[31]
Shakeri A, Amini E, Asili J, Masullo M, Piacente S, Iranshahi M. Screening of several biological activities induced by different sesquiterpene lactones isolated from Centaurea behen L. and Rhaponticum repens (L.) Hidalgo. Nat Prod Res 2018; 32: 1436-40.
[http://dx.doi.org/10.1080/14786419.2017.1344661]
[32]
Kabala-Dzik A, Rzepecka-Stojko A, Kubina R, et al. Migration rateinhibition of breast cancer cells treated by caffeic acid and caffeic acid phenethyl ester: An in vitro comparison study. Nutrients 2017; 9(10): 1144.
[http://dx.doi.org/10.3390/nu9101144]
[33]
He H, Zheng L, Sun YP, Zhang GW, Yue ZG. Steroidal saponins from Paris polyphylla suppress adhesion, migration and invasion of human lung cancer A549 cells via down-regulating MMP-2 and MMP-9. APJCP 2014; 15: 10911-6.
[34]
Liew SY, Looi CY, Paydar M, et al. Subditine, a new monoterpenoid indole alkaloid from bark of Nauclea subdita (Korth.) Steud. induces apoptosis in human prostate cancer cells. PLoS One 2014; 9: e87286-98.
[http://dx.doi.org/10.1371/journal.pone.0087286]
[35]
Coradini D, Boracchi P, Oriana S, Biganzoli E, Ambrogi F. Epithelial cell identity in hyperplastic precursors of breast cancer. Chin J Cancer 2015; 34: 121-9.
[http://dx.doi.org/10.1186/s40880-015-0004-z]
[36]
Klein CA. Selection and adaptation during metastatic cancer progression. Nature 2013; 501: 365-72.
[http://dx.doi.org/10.1038/nature12628]
[37]
Vu T, Datta PK. Regulation of EMT in colorectal cancer: A culprit in metastasis. Cancers (Basel) 2017; 9: 171-92.
[http://dx.doi.org/10.3390/cancers9120171]
[38]
Gilkes DM. Implications of hypoxia in breast cancer metastasis to bone. Int J Mol Sci 2016; 17: 1669-82.
[http://dx.doi.org/10.3390/ijms17101669]
[39]
Amaro A, Angelini G, Mirisola V, et al. A highly invasive subpopulation of MDA-MB-231 breast cancer cells shows accelerated growth, differential chemoresistance, features of apocrine tumors and reduced tumorigenicity in vivo. Oncotarget 2016; 7: 68803-20.
[http://dx.doi.org/10.18632/oncotarget.11931]
[40]
Wang H, Khor TO, Shu L, et al. Plants vs. cancer: A review on natural phytochemicals in preventing and treating cancers and their druggability. Anticancer Agents Med Chem 2012; 12: 1281-305.
[http://dx.doi.org/10.2174/187152012803833026]
[41]
Chicca A, Tebano M, Adinolfi B, Ertugrul K, Flamini G, Nieri P. Anti-proliferative activity of aguerin B and a new rare nor-guaianolide lactone isolated from the aerial parts of Centaurea deflexa. Eur J Med Chem 2011; 46: 3066-70.
[http://dx.doi.org/10.1016/j.ejmech.2011.03.011]
[42]
Zhou Y, Liao Q, Han Y, et al. Rac1 overexpression is correlated with epithelial mesenchymal transition and predicts poor prognosis in non-small cell lung cancer. J Cancer 2016; 7: 2100-9.
[http://dx.doi.org/10.7150/jca.16198]
[43]
Kamai T, Shirataki H, Nakanishi K, et al. Increased Rac1 activity and Pak1 overexpression are associated with lymphovascular invasion and lymph node metastasis of upper urinary tract cancer. BMC Cancer 2010; 10: 164-76.
[http://dx.doi.org/10.1186/1471-2407-10-164]
[44]
Hammer A, Diakonova M. Tyrosyl phosphorylated serine-threonine kinase PAK1 is a novel regulator of prolactin-dependent breast cancer cell motility and invasion. Adv Exp Med Biol 2015; 846: 97-137.
[http://dx.doi.org/10.1007/978-3-319-12114-7_5]
[45]
Yang Z, Wang H, Xia L, et al. Overexpression of PAK1 correlates with aberrant expression of EMT markers and poor prognosis in non-small cell lung cancer. J Cancer 2017; 8: 1484-91.
[http://dx.doi.org/10.7150/jca.18553]
[46]
Ghalib RM, Hashim R, Sulaiman O, et al. A novel caryophyllene type sesquiterpene lactone from Asparagus falcatus (Linn.); Structure elucidation and anti-angiogenic activity on HUVECs. Eur J Med Chem 2012; 47: 601-7.
[http://dx.doi.org/10.1016/j.ejmech.2011.10.037]
[47]
Zhong ZF, Hoi PM, Wu GS, et al. Anti-angiogenic effect of furanodiene on HUVECs in vitro and on zebrafish in vivo. J Ethnopharmacol 2012; 141: 721-7.
[http://dx.doi.org/10.1016/j.jep.2011.08.052]
[48]
Yue GG, Chan BC, Kwok HF, et al. Anti-angiogenesis and immunomodulatory activities of an anti-tumor sesquiterpene bigelovin isolated from Inula helianthus-aquatica. Eur J Med Chem 2013; 59: 243-52.
[http://dx.doi.org/10.1016/j.ejmech.2012.11.029]
[49]
de Oliveira Mauro M, Matuo R, de David N, et al. Actions of sesquiterpene lactones isolated from Moquiniastrum polymorphum subsp. floccosum in MCF7 cell line and their potentiating action on doxorubicin. BMC Pharmacol Toxicol 2017; 18: 53.
[http://dx.doi.org/10.1186/s40360-017-0156-3]
[50]
Tabata K, Nishimura Y, Takeda T, Kurita M, Uchiyama T, Suzuki T. Sesquiterpene lactones derived from Saussurea lappa induce apoptosis and inhibit invasion and migration in neuroblastoma cells. J Pharmacol Sci 2015; 127: 397-403.
[http://dx.doi.org/10.1016/j.jphs.2015.01.002]
[51]
Nakagawa-Goto K, Chen J-Y, Cheng Y-T, et al. Novel sesquiterpene lactone analogues as potent anti-breast cancer agents. Mol Oncol 2016; 10: 921-37.
[http://dx.doi.org/10.1016/j.molonc.2016.03.002]
[52]
Liu J, Liu M, Wang S, et al. Alantolactone induces apoptosis and suppresses migration in MCF7 human breast cancer cells via the p38 MAPK, NFkappaB and NRF2 signaling pathways. Int J Mol Med 2018; 42: 1847-56.
[http://dx.doi.org/10.3892/ijmm.2018.3751]
[53]
Wang W, Chen B, Zou R, et al. Codonolactone, a sesquiterpene lactone isolated from Chloranthus henryi Hemsl, inhibits breast cancer cell invasion, migration and metastasis by downregulating the transcriptional activity of Runx2. Int J Oncol 2014; 45: 1891-900.
[http://dx.doi.org/10.3892/ijo.2014.2643]