Author(s): Tran Thanh Long, Do Thi Phuong Linh, Dang Minh Phuc, Dang Thi Phuong Thao, Nguyen Thi My Trinh

Email(s): ntmtrinh@hcmus.edu.vn

DOI: 10.52711/0974-360X.2025.00828   

Address: Tran Thanh Long1, Do Thi Phuong Linh1, Dang Minh Phuc1, Dang Thi Phuong Thao1,2,3,4, Nguyen Thi My Trinh1,2*
1Department of Molecular and Environmental Biotechnology, Faculty of Biology and Biotechnology, VNUHCM-University of Science, 227 Nguyen Van Cu, Ho Chi Minh City, 700000, Viet Nam.
2Laboratory of Molecular Biotechnology, VNUHCM- University of Science, 227 Nguyen Van Cu, Ho Chi Minh City, 700000, Viet Nam.
3Laboratory of Cancer Research, VNUHCM- University of Science, 227 Nguyen Van Cu, Ho Chi Minh City, 700000, Viet Nam.
4Vietnam National University-Ho Chi Minh City, Linh Xuan Ward, Ho Chi Minh city, 700000, Viet Nam.
*Corresponding Author

Published In:   Volume - 18,      Issue - 12,     Year - 2025


ABSTRACT:
Extracts and compounds from Elephantopus mollis (EM), a relatively well-studied herbal plant of the Asteraceae family, were proved to be substantially cytotoxic toward various cancers, including cervical carcinoma. Nevertheless, the anti-metastatic ability of this plant remains unknown. Hence, in this study, we evaluated the influence of EM extracts on the migration, invasion, and adhesion of cervical cancer SiHa cells. The non-toxic thresholds of EM extracts were identified by MTT assay and microscopic observation. Wound healing assay was employed to evaluate the effect of EM extracts on cell migration. Geltrex-coated Transwell assay, and Collagen I adhesion assessment were harnessed for cancer cell invasion and extra cellular matrix attachment, respectively. The expressions of metastasis-involved genes under the influence of chosen EM extract were quantified by RT-qPCR. The sub-lethal concentrations of EM extracts were tested on SiHa cell migratory ability via wound healing assay. Among the four extracts (ethyl acetate, ethanol, water, and petroleum ether), ethyl acetate fraction (EM-EA) was chosen due to its effectiveness at very low concentrations (i.e., 5 and 10µg/mL extract reduce cell migration by 26% and 54%, respectively). Assessment of cellular invasion and adhesion indicated the significant inhibition of EM-EA on the ability to invade the basement membrane and attach to the ECM of SiHa cells, respectively. Finally, a 40% reduced expression of a crucial metastasis-involved gene (i.e., EZR) caused by EM-EA treatment suggested the underlying mechanism of this extract on the metastasis of SiHa cells. Collectively, our findings are the first to demonstrate the effects of EM extracts on the metastatic traits of cervical cancer cells and its underline mechanism.


Cite this article:
Tran Thanh Long, Do Thi Phuong Linh, Dang Minh Phuc, Dang Thi Phuong Thao, Nguyen Thi My Trinh. The effects of Elephantopus mollis Extracts on the Migration, Invasion and Adhesion of Human Cervical Cancer Cells. Research Journal Pharmacy and Technology. 2025;18(12):5739-8 doi: 10.52711/0974-360X.2025.00828

Cite(Electronic):
Tran Thanh Long, Do Thi Phuong Linh, Dang Minh Phuc, Dang Thi Phuong Thao, Nguyen Thi My Trinh. The effects of Elephantopus mollis Extracts on the Migration, Invasion and Adhesion of Human Cervical Cancer Cells. Research Journal Pharmacy and Technology. 2025;18(12):5739-8 doi: 10.52711/0974-360X.2025.00828   Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2025-18-12-18


10. REFERENCES:
1.    Cervical cancer. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/cervical-cancer#:~:text=Cervical cancer is the fourth,- and middle-income countries.
2.    Tekalign T, Teshome M. Prevalence and determinants of late-stage presentation among cervical cancer patients, a systematic review and meta-analysis. PLoS One. 2022; 17(4): e0267571. https://doi.org/10.1371/journal.pone.0267571
3.    Sen A, Kumar K, Khan S, Pathak P, Singh A. Current Therapy in Cancer: Advances, Challenges, and Future Directions. Asian J Nurs Educ Res. 2024; 14(1): 77-84.
4.    Iranmanesh S, Shamsi A. The Relationship between Type of Cancer and Parent’s Psychosocial Risks. Asian J Nurs Educ Res. 2014; 4(4): 496-502.
5.    Singh D, Vignat J, Lorenzoni V, et al. Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative. Lancet Glob Heal. 2023; 11(2): e197-e206. doi:10.1016/S2214-109X(22)00501-0
6.    Gandalovičová A, Rosel D, Fernandes M, et al. Migrastatics-Anti-metastatic and Anti-invasion Drugs: Promises and Challenges. Trends in Cancer. 2017; 3(6): 391-406. doi:10.1016/j.trecan.2017.04.008
7.    Anderson RL, Balasas T, Callaghan J, et al. A framework for the development of effective anti-metastatic agents. Nat Rev Clin Oncol. 2019; 16(3): 185-204. doi:10.1038/s41571-018-0134-8
8.    Hanna K, Mayden K. Chemotherapy Treatment Considerations in Metastatic Breast Cancer. J Adv Pract Oncol. 2021; 12(Suppl 2): 6-12. doi:10.6004/jadpro.2021.12.2.11
9.    Wibowo BP, Kalim H, Khotimah H, Sujuti H, Rukmigarsari E. TLR4/NF-kB/β-Catenin/TGF-β pathways in Salmonella AvrA related-Colorectal Cancer Tumorigenesis. Res J Pharm Technol. 2024; 17(6): 2597-2604.
10.    Murwanti R, Kholifah E, Sudarmanto BS, Hermawan A. Curcumin and its Analogue Targeting β-Catenin and GSK-3β in Wnt Signaling Pathways: In Vitro and In Silico Study. Res J Pharm Technol. 2020; 13(4): 1715-1719.
11.    Ortiz-Otero N, Marshall JR, Lash B, King MR. Chemotherapy-induced release of circulating-tumor cells into the bloodstream in  collective migration units with cancer-associated fibroblasts in metastatic cancer patients. BMC Cancer. 2020; 20(1): 873. doi:10.1186/s12885-020-07376-1
12.    Consortium TWFO, Elliott A, Hyam R, et al. World Flora Online Plant List June 2024. Published online June. 2024. doi:10.5281/zenodo.12171908
13.    Gibert-Tisseuil F. [Reflections on traditional Chinese medicine and its pharmacopoeia]. Ann Pharm Fr. 1998; 56(6): 282-285.
14.    Yang J, Li ZD, Hou CY, et al. EM-2 inhibited autophagy and promoted G(2)/M phase arrest and apoptosis by  activating the JNK pathway in hepatocellular carcinoma cells. Acta Pharmacol Sin. 2021; 42(7): 1139-1149. doi:10.1038/s41401-020-00564-6
15.    Kabiru A, Por LY. Elephantopus Species: Traditional Uses, Pharmacological Actions and Chemical Composition. Adv Life Sci Technol. 2013; 15: 6-13. https://api.semanticscholar.org/CorpusID:44056446
16.    Tabopda TK, Ngoupayo J, Liu J, et al. Further cytotoxic sesquiterpene lactones from Elephantopus mollis KUNTH. Chem Pharm Bull (Tokyo). 2008; 56(2): 231-233. doi:10.1248/cpb.56.231
17.    Bich Ngoc TT, Hoai Nga NT, My Trinh NT, Thuoc TL, Phuong Thao DT. Elephantopus mollis Kunth extracts induce antiproliferation and apoptosis in human lung cancer and myeloid leukemia cells. J Ethnopharmacol. 2020; 263: 113222. doi:https://doi.org/10.1016/j.jep.2020.113222
18.    Kuete V, Fokou FW, Karaosmanoğlu O, Beng VP, Sivas H. Cytotoxicity of the methanol extracts of Elephantopus mollis, Kalanchoe crenata and 4 other Cameroonian medicinal plants towards human carcinoma cells. BMC Complement Altern Med. 2017; 17(1): 280. doi:10.1186/s12906-017-1793-1
19.    Ooi KL, Tengku Muhammad TS, Lam LY, Sulaiman SF. Cytotoxic and Apoptotic Effects of Ethyl Acetate Extract of Elephantopus mollis  Kunth. in Human Liver Carcinoma HepG2 Cells Through Caspase-3 Activation. Integr Cancer Ther. 2014; 13(3): NP1-9. doi:10.1177/1534735411433203
20.    Tam TDT, Ngoc TTB, Nga NTH, Trinh NTM, Thuoc TL, Thao DTP. Ethyl acetate extract of Elephantopus mollis Kunth induces apoptosis in human gastric cancer cells. BMC Complement Med Ther. 2021; 21(1): 273. doi:10.1186/s12906-021-03444-6
21.    Lee KH, Ibuka T, Furukawa H, et al. Antitumor agents XXXVIII: Isolation and structural elucidation of novel germacranolides and triterpenes from Elephantopus mollis. J Pharm Sci. 1980; 69(9): 1050-1056. doi:https://doi.org/10.1002/jps.2600690917
22.    Tabopda  Jiawei; Ngadjui, Bonaventure Tchaleu; Luu, Bang TKL. Cytotoxic Triterpene and Sesquiterpene Lactones from Elephantopus mollis and Induction of Apoptosis in Neuroblastoma Cells. Planta Med. 2007; 73(04): 376-380. doi:10.1055/s-2007-967132
23.    HUANG X, YANG J, HE P yan, et al. Molecular Mechanism of Inducing 2774-C10 Cell Apoptosis and G1/S Cell Cycle Arrest by Ethanol Extract from Elephantopus mollis H.B.K. China Biotechnol. 2018; 38(4):17-23. doi:10.13523/j.cb.20180403
24.    Li J, Zhou J, Zhao N, et al. EM-2, a natural sesquiterpene lactone from Elephantopus mollis H.B.K., enhanced the sensitivity of breast cancer cells to epirubicin by blocking protective autophagy. Phytomedicine. 2023; 116: 154878. doi:https://doi.org/10.1016/j.phymed.2023.154878
25.    Li H, Li M, Wang G, et al. EM23, A Natural Sesquiterpene Lactone from Elephantopus mollis, Induces Apoptosis in Human Myeloid Leukemia Cells through Thioredoxin- and Reactive Oxygen Species-Mediated Signaling Pathways. Front Pharmacol. 2016;7. https://www.frontiersin.org/articles/10.3389/fphar.2016.00077
26.    Shao FY, Wang S, Li HY, et al. EM23, a natural sesquiterpene lactone, targets thioredoxin reductase to activate  JNK and cell death pathways in human cervical cancer cells. Oncotarget. 2016; 7(6): 6790-6808. doi:10.18632/oncotarget.6828
27.    Bheda A, Shackelford J, Pagano JS. Expression and functional studies of ubiquitin C-terminal hydrolase L1 regulated  genes. PLoS One. 2009; 4(8): e6764. doi:10.1371/journal.pone.0006764
28.    Sung CO, Lee KW, Han S, Kim SH. Twist1 is up-regulated in gastric cancer-associated fibroblasts with poor  clinical outcomes. Am J Pathol. 2011; 179(4): 1827-1838. doi:10.1016/j.ajpath.2011.06.032
29.    Goyal A, Martin TA, Mansel RE, Jiang WG. Real time PCR analyses of expression of E-cadherin, alpha-, beta- and  gamma-catenin in human breast cancer for predicting clinical outcome. World J Surg Oncol. 2008; 6: 56. doi:10.1186/1477-7819-6-56
30.    Medici D, Hay ED, Olsen BR. Snail and Slug promote epithelial-mesenchymal transition through  beta-catenin-T-cell factor-4-dependent expression of transforming growth factor-beta3. Mol Biol Cell. 2008; 19(11): 4875-4887. doi:10.1091/mbc.e08-05-0506
31.    Zeng H, Xu L, Xiao D, et al. Altered Expression of Ezrin in Esophageal Squamous Cell Carcinoma. J Histochem Cytochem. 2006; 54(8): 889-896. doi:10.1369/jhc.5A6881.2006
32.    Vang Mouritzen M, Jenssen H. Optimized Scratch Assay for In Vitro Testing of Cell Migration with an Automated  Optical Camera. J Vis Exp. 2018; (138). doi:10.3791/57691
33.    Pijuan J, Barceló C, Moreno DF, et al. In vitro Cell Migration, Invasion, and Adhesion Assays: From Cell Imaging to Data  Analysis. Front cell Dev Biol. 2019; 7: 107. doi:10.3389/fcell.2019.00107
34.    Sun B. The mechanics of fibrillar collagen extracellular matrix. Cell reports Phys Sci. 2021;2(8). doi:10.1016/j.xcrp.2021.100515
35.    Zhou S, Peng F. Patterns of metastases in cervical cancer: a population-based study. Int J Clin Exp Pathol. 2020; 13(7): 1615-1623.
36.    Dhawan D, Gupta J. Research article comparison of different solvents for phytochemical extraction potential from datura metel plant leaves. Int J Biol Chem. 2017; 11(1): 17-22.
37.    Engwa GA, Nnamdi P, Nnadi JC, Offor TI, Eze BC. Comparative qualitative analysis of the phytochemical load of water, methanol, ethyl acetate and hexane extracts of six selected medicinal plants. Int J Pharmacogn Phytochem Res. 2013; 5(3): 164-167.
38.    Loc L, Thao D, Nhi N, Quan T. Study on chemical constituents of the ethyl acetate extract of Elephantopus mollis. Sci & Technol Dev J Nat Sci. 2023; 7(4 SE-Original Research). doi:https://doi.org/10.32508/stdjns.v7i4.1251
39.    Abotaleb M, Liskova A, Kubatka P, Büsselberg D. Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer. Biomolecules. 2020; 10(2). doi:10.3390/biom10020221
40.    Anantharaju PG, Gowda PC, Vimalambike MG, Madhunapantula S V. An overview on the role of dietary phenolics for the treatment of cancers. Nutr J. 2016; 15(1): 99. doi:10.1186/s12937-016-0217-2
41.    Chiou WF, Chen CC, Wei BL. 3,4-Di-O-Caffeoylquinic Acid Inhibits Angiotensin-II-Induced Vascular Smooth  Muscle Cell Proliferation and Migration by Downregulating the JNK and PI3K/Akt Signaling Pathways. Evid Based Complement Alternat Med. 2011; 2011: 634502. doi:10.1093/ecam/nep140
42.    Li Q, Niu JQ, Jia JH, et al. A highly oxidized germacranolide from elephantopus tomentosus inhibits the growth of hepatocellular carcinoma cells by targeting EGFR in vitro and in vivo. Bioorg Chem. 2024; 143: 107007. doi:https://doi.org/10.1016/j.bioorg.2023.107007
43.    Hiradeve SM, Rangari VD. Elephantopus scaber Linn.: A review on its ethnomedical, phytochemical and pharmacological profile. J Appl Biomed. 2014; 12(2): 49-61. doi:https://doi.org/10.1016/j.jab.2014.01.008
44.    Gao Y, Nie Z, Cao H, et al. Scabertopin Derived from Elephantopus scaber L. Mediates Necroptosis by Inducing  Reactive Oxygen Species Production in Bladder Cancer In Vitro. Cancers (Basel). 2022; 14(23). doi:10.3390/cancers14235976
45.    Farha AK, Dhanya SR, Mangalam SN, Remani P. Anti-metastatic effect of deoxyelephantopin from Elephantopus scaber in A549 lung  cancer cells in vitro. Nat Prod Res. 2015; 29(24): 2341-2345. doi:10.1080/14786419.2015.1012165
46.    Nakagawa-Goto K, Chen JY, Cheng YT, et al. Novel sesquiterpene lactone analogues as potent anti-breast cancer agents. Mol Oncol. 2016; 10(6): 921-937. doi:https://doi.org/10.1016/j.molonc.2016.03.002
47.    Ruggieri F, Hance P, Gioia B, et al. A Three-Step Process to Isolate Large Quantities of Bioactive Sesquiterpene  Lactones from Cichorium intybus L. Roots and Semisynthesis of Chicory STLs Standards. Pharmaceuticals (Basel). 2023; 16(5). doi:10.3390/ph16050771
48.    Ivanescu B, Miron A, Corciova A. Sesquiterpene Lactones from Artemisia Genus: Biological Activities and Methods of  Analysis. J Anal Methods Chem. 2015; 2015: 247685. doi:10.1155/2015/247685
49.    Yayan J, Franke KJ, Berger M, Windisch W, Rasche K. Adhesion, metastasis, and inhibition of cancer cells: a comprehensive review. Mol Biol Rep. 2024; 51(1): 165. doi:10.1007/s11033-023-08920-5
50.    Duś-Szachniewicz K, Drobczyński S, Woźniak M, et al. Differentiation of single lymphoma primary cells and normal B-cells based on  their adhesion to mesenchymal stromal cells in optical tweezers. Sci Rep. 2019; 9(1): 9885. doi:10.1038/s41598-019-46086-y
51.    Liu S, Liao G, Li G. Regulatory effects of COL1A1 on apoptosis induced by radiation in cervical cancer cells. Cancer Cell Int. 2017; 17: 73. doi:10.1186/s12935-017-0443-5
52.    Li J, Wei K, Yu H, Jin D, Wang G, Yu B. Prognostic value of ezrin in various cancers: a systematic review and updated meta-analysis. Sci Rep. 2015; 5(1): 17903.
53.    Song Y, Ma X, Zhang M, et al. Ezrin Mediates Invasion and Metastasis in Tumorigenesis: A Review. Front Cell Dev Biol. 2020; 8. https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.588801
54.    Rambabu M, Kanggeyavelu J, Jayanthi S. Tight junctions and their role in cancer: A review. Res J Pharm Technol. 2018; 11(8): 3561-3571.
55.    Tilston-Lünel AM, Haley KE, Schlecht NF, et al. Crumbs 3b promotes tight junctions in an ezrin-dependent manner in mammalian  cells. J Mol Cell Biol. 2016; 8(5): 439-455. doi:10.1093/jmcb/mjw020
56.    Liu J, Xiao Q, Xiao J, et al. Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities. Signal Transduct Target Ther. 2022; 7(1): 3. doi:10.1038/s41392-021-00762-6
57.    Hiscox S, Jiang WG. Ezrin regulates cell-cell and cell-matrix adhesion, a possible role with E-cadherin/β-catenin. J Cell Sci. 1999; 112(18): 3081-3090. doi:10.1242/jcs.112.18.3081
58.    Shankari B, Rambabu M, Jayanthi S. Identification and Designing Inhibitors for Hepatocellular Carcinoma by Targeting Claudin-10. Res J Pharm Technol. 2018; 11(8): 3529-3533.
59.    Fatimah S, Rahaju AS, Rahniayu A. Role of claudin-4 and matrix metalloproteinase-2 in tumor invasion of colorectal adenocarcinoma. Res J Pharm Technol. 2021; 14(9): 4795-4800.
60.    Shankari B, Rambabu M, Jayanthi S. Claudin-7 Inhibitors for Colon Cancer: A Computational Approach. Res J Pharm Technol. 2018; 11(8): 3415-3418.
61.    Zhao Z, Rahman MA, Chen ZG, Shin DM. Multiple biological functions of Twist1 in various cancers. Oncotarget. 2017; 8(12): 20380-20393. doi:10.18632/oncotarget.14608
62.    Kaufhold S, Bonavida B. Central role of Snail1 in the regulation of EMT and resistance in cancer: a target for therapeutic intervention. J Exp Clin Cancer Res. 2014; 33(1): 62. doi:10.1186/s13046-014-0062-0
63.    Chang YT, Peng HY, Hu CM, Huang SC, Tien SC, Jeng YM. Pancreatic cancer-derived small extracellular vesical Ezrin regulates macrophage polarization and promotes metastasis. Am J Cancer Res. 2020; 10(1): 12.
64.    Ren L, Khanna C. Role of ezrin in osteosarcoma metastasis. Curr Adv Osteosarcoma. Published online 2014: 181-201.
65.    Kocher HM, Sandle J, Mirza TA, Li NF, Hart IR. Ezrin interacts with cortactin to form podosomal rosettes in pancreatic cancer cells. Gut. 2009; 58(2): 271-284.




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