Download PDF
Planta Med 2024; 90(01): 13-24
DOI: 10.1055/a-2181-2569
Biological and Pharmacological Activity
Original Papers

Tapirira guianensis is Selectively Cytotoxic, Induces Apoptosis to the Glioblastoma and Decreases Tumor Growth and Angiogenesis in vivo

Ana Gabriela Silva Oliveira
1   Experimental Pathology Laboratory, Midwest Campus, Federal University of São João del-Rei, Divinópolis, Brazil
,
Marina Andrade Rocha
1   Experimental Pathology Laboratory, Midwest Campus, Federal University of São João del-Rei, Divinópolis, Brazil
,
Lucas Santos de Azevedo
1   Experimental Pathology Laboratory, Midwest Campus, Federal University of São João del-Rei, Divinópolis, Brazil
,
Aline Thaynara de Moura Coelho
1   Experimental Pathology Laboratory, Midwest Campus, Federal University of São João del-Rei, Divinópolis, Brazil
,
Rafael César Russo Chagas
1   Experimental Pathology Laboratory, Midwest Campus, Federal University of São João del-Rei, Divinópolis, Brazil
,
Hélio Batista Santos
2   Tissue Processing Laboratory, Midwest Campus, Federal University of São João del-Rei, Divinópolis, Brazil
,
Ralph Gruppi Thomé
2   Tissue Processing Laboratory, Midwest Campus, Federal University of São João del-Rei, Divinópolis, Brazil
,
Peter Samuel
3   Zurich University of Applied Sciences, Department of Life Sciences and Facility Management, Wädenswil, Switzerland
,
Evelyn Wolfram
3   Zurich University of Applied Sciences, Department of Life Sciences and Facility Management, Wädenswil, Switzerland
,
Bonglee Kim
4   Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
,
Rui Manuel Reis
5   Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil
6   Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Portugal
,
Rosy Iara Maciel Azambuja Ribeiro 
1   Experimental Pathology Laboratory, Midwest Campus, Federal University of São João del-Rei, Divinópolis, Brazil
› Author AffiliationsThe authors are grateful for the research support provided by the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG – PPM-00229-16 and APQ-00068-18) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES – Finance Code 001). This research was also supported by FINEP (MCTI/FINEP/MS/SCTIE/DECIT-01/2013, FPXII-BIOPLAT). Furthermore, we thank all other parties who made this study possible.
› Further Information
Also available at
   Permissions and Reprints

Abstract

Glioblastoma is the most frequent primary malignant brain tumor without effective treatment, which makes this work extremely relevant. The study of the bioactive compounds from medicinal plants plays an important role in the discovery of new drugs.

This research investigated the constituents of Tapirira guianensis and its antitumor potential (in vitro and in vivo) in glioblastoma. The T. guianensis extracts were characterized by mass spectrometry. The ethyl acetate partition (01ID) and its fractions 01ID-F2 and 01ID-F4 from T. guianensis showed potential antitumor treatment evidenced by selective cytotoxicity for GAMG with IC50 14.1 µg/mL, 83.07 µg/mL, 59.27 µg/mL and U251 with IC50 25.92 µg/mL, 37.3 µg/mL and 18.84 µg/mL. Fractions 01ID-F2 and 01ID-F4 were 10 times more selective when compared to TMZ and 01ID for the two evaluated cell lines. T. guianensis also reduced matrix metalloproteinases 2 – 01ID-F2 (21.84%), 01ID-F4 (29.6%) and 9 – 01ID-F4 (73.42%), ID-F4 (53.84%) activities, and induced apoptosis mainly through the extrinsic pathway. Furthermore, all treatments significantly reduced tumor size (01ID p < 0,01, 01ID-F2 p < 0,01 and 01ID-F4 p < 0,0001) and caused blood vessels to shrink in vivo. The present findings highlight that T. guianensis exhibits considerable antitumor potential in preclinical studies of glioblastoma. This ability may be related to the phenolic compounds and sesquiterpene derivatives identified in the extracts. This study deserves further in vivo research, followed by clinical investigation.

Key words

Glioblastoma - cerrado - Tapirira guianensis - Anacardiaceae - apoptosis - angiogenesis

Supporting Information

    The effects used in the Western blotting assay and their concentrations are described in the supplemental material.

  • Supporting Information


Publication History

Received: 05 April 2023

Accepted after revision: 19 September 2023

Article published online:
13 October 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Lapointe S, Perry A, Butowski NA. Primary brain tumors in adults. The Lancet 2018; 392: 432-446
    CrossrefPubMedSearch in Google Scholar
  • 2 Grochans S, Cybulska AM, Simińska D, Korbecki J, Kojder K, Chlubek D, Baranowska-Bosiacka I. Epidemiology of glioblastoma multiforme–Literature review. Cancers (Basel) 2022; 14: 2412
    CrossrefPubMedSearch in Google Scholar
  • 3 Ravi VM, Will P, Kueckelhaus J, Sun N, Joseph K, Salié H, Heiland DH. Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma. Cancer Cell 2022; 40 (06) 639-655
    CrossrefPubMedSearch in Google Scholar
  • 4 Alifieris C, Trafalis D. T Glioblastoma multiforme: Pathogenesis and treatment. Pharmacol Ther 2015; 152: 63-82
    CrossrefPubMedSearch in Google Scholar
  • 5 Gupta T, Talukdar R, Kannan S, Dasgupta A, Chatterjee A, Patil V. Efficacy and safety of extended adjuvant temozolomide compared to standard adjuvant temozolomide in glioblastoma: Updated systematic review and meta-analysis. Neurooncol Pract 2022; 9: 354-363
    PubMedSearch in Google Scholar
  • 6 Park MN, Song HS, Kim M, Lee MJ, Cho W, Lee HJ, Kim B. Review of natural product-derived compounds as potent antiglioblastoma drugs. Biomed Res Int 2017; 2017: 8139848
    PubMedSearch in Google Scholar
  • 7 Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 2016; 79: 629-661
    CrossrefPubMedSearch in Google Scholar
  • 8 Calixto JB. The role of natural products in modern drug discovery. An Acad Bras Cienc 2019; 91 (Suppl. 03) (Suppl3)
    PubMedSearch in Google Scholar
  • 9 Silva-Oliveira RJ, Lopes GF, Camargos LF, Ribeiro AM, Santos FV, Severino RP, Severino VG, Terezan AP, Thomé RG, Santos HB, Reis RM, Ribeiro RI. Tapirira guianensis Aubl. Extracts inhibit proliferation and migration of oral cancer cells lines. Int J Mol Sci 2016; 17 (11) 1839
    CrossrefPubMedSearch in Google Scholar
  • 10 Longatti TR, Cenzi G, Lima LARS, Oliveira RJS, Oliveira VN, Da Silva SL, Ribeiro RIMA. Inhibition of gelatinases by vegetable extracts of the species Tapirira guianensis (Stick Pigeon). British Journal of Pharmaceutical Research 2011; 1: 133
    CrossrefPubMedSearch in Google Scholar
  • 11 Stockhammer F. Treatment of glioblastoma in elderly patients. CNS Oncol 2014; 3: 159-167
    CrossrefPubMedSearch in Google Scholar
  • 12 Tan AC, Ashley DM, López GY, Malinzak M, Friedman HS, Khasraw M. Management of glioblastoma: State of the art and future directions. CA Cancer J Clin 2020; 70 (04) 299-312
    CrossrefPubMedSearch in Google Scholar
  • 13 Silva AG, Lopes CFB, Júnior CGC, Thomé RG, Dos Santos HB, Reis R, Ribeiro RIMA. MWIN55, 212-2 induces caspase-independent apoptosis on human glioblastoma cells by regulating HSP70, p 53 and Cathepsin D. Toxicol In Vitro 2019; 57: 233-243
    CrossrefPubMedSearch in Google Scholar
  • 14 Indrayanto G, Putra GS, Suhud F. Validation of in-vitro bioassay methods: Application in herbal drug research. Profiles Drug Subst Excip Relat Methodol 2021; 46: 273-307
    CrossrefPubMedSearch in Google Scholar
  • 15 He Y, Zhao C, Liu Y, He Z, Zhang Z, Gao Y, Jiang J. RETRACTED ARTICLE: MiR-124 functions as a tumor suppressor via targeting hCLOCK1 in glioblastoma. Mol Neurobiol 2017; 54: 2375
    CrossrefPubMedSearch in Google Scholar
  • 16 Abba M, Patil N, Allgayer H. MicroRNAs in the regulation of MMPs and metastasis. Cancers (Basel) 2014; 6 (02) 625-645
    CrossrefPubMedSearch in Google Scholar
  • 17 Memmel S, Sukhorukov VL, Höring M, Westerling K, Fiedler V, Katzer A, Krohne G, Flentje M, Djuzenova CS. Cell surface area and membrane folding in glioblastoma cell lines differing in PTEN and p 53 status. PLoS One 2014; 9: e87052
    CrossrefPubMedSearch in Google Scholar
  • 18 Xie Q, Mittal S, Berens ME. Targeting adaptive glioblastoma: An overview of proliferation and invasion. Neuro Oncol 2014; 16 (12) 1575-1584
    CrossrefPubMedSearch in Google Scholar
  • 19 Rachlin K, Moore DH, Yount G. Infrasound sensitizes human glioblastoma cells to cisplatin-induced apoptosis. Integr Cancer Ther 2013; 12 (06) 517-527
    CrossrefPubMedSearch in Google Scholar
  • 20 Pezzani R, Salehi B, Vitalini S, Iriti M, Zuñiga FA, Sharifi-Rad J, Martins N. Synergistic effects of plant derivatives and conventional chemotherapeutic agents: An update on the cancer perspective. Medicina (Kaunas) 2019; 55 (04) 110
    CrossrefPubMedSearch in Google Scholar
  • 21 Pistritto G, Trisciuoglio D, Ceci C, Garufi A, DʼOrazi G. Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies. Aging 2016; 8: 603-619
    CrossrefPubMedSearch in Google Scholar
  • 22 Abotaleb M, Samuel SM, Varghese E, Varghese S, Kubatka P, Liskova A, Büsselberg D. Flavonoids in cancer and apoptosis. Cancers (Basel) 2019; 1 (01) 28
    CrossrefPubMedSearch in Google Scholar
  • 23 Tsai YJ, Chen BH. Preparation of catechin extracts and nanoemulsions from green tea leaf waste and their inhibition effect on prostate cancer cell PC-3. Int J Nanomedicine 2016; 11: 1907-1926
    PubMedSearch in Google Scholar
  • 24 Wang LX, Shi YL, Zhang LJ, Wang KR, Xiang LP, Cai ZY, Zheng XQ. Inhibitory effects of (−)-Epigallocatechin-3-gallate on Esophageal cancer. Molecules 2019; 24 (05) 954
    CrossrefPubMedSearch in Google Scholar
  • 25 Kohn EC, Liotta LA. Molecular insights into cancer invasion: Strategies for prevention and intervention. Cancer Res 1995; 55 (09) 1856-1862
    PubMedSearch in Google Scholar
  • 26 Liu Y, Tang ZG, Yang JQ, Zhou Y, Meng LH, Wang H, Li CL. Low concentration of quercetin antagonizes the invasion and angiogenesis of human glioblastoma U251 cells. Onco Targets Ther 2017; 10: 4023-4028
    CrossrefPubMedSearch in Google Scholar
  • 27 Santos BL, Oliveira MN, Coelho PL, Pitanga BP, Da Silva AB, Adelita T, Costa SL. Flavonoids suppress human glioblastoma cell growth by inhibiting cell metabolism, migration, and by regulating extracellular matrix proteins and metalloproteinases expression. Chem Biol Interact 2015; 242: 123-137
    CrossrefPubMedSearch in Google Scholar
  • 28 Han L, Zhang HW, Zhou WP, Chen GM, Guo KJ. The effects of genistein on transforming growth factor-β1-induced invasion and metastasis in human pancreatic cancer cell line Panc-1 in vitro. Chin Med J (Engl) 2012; 125 (11) 2032-2040
    PubMedSearch in Google Scholar
  • 29 Yang CS, Wang H. Cancer preventive activities of tea catechins. Molecules 2016; 21 (11) 2032-2040
    PubMedSearch in Google Scholar
  • 30 Busch M, Philippeit C, Weise A, Dünker N. Re-characterization of established human retinoblastoma cell lines. Histochem Cell Biol 2015; 143 (03) 325-338
    CrossrefPubMedSearch in Google Scholar
  • 31 Dünker N, Jendrossek V. Implementation of the Chick Chorioallantoic Membrane (CAM) model in radiation biology and experimental radiation oncology research. Cancers (Basel) 2019; 11 (10) 1499
    CrossrefPubMedSearch in Google Scholar
  • 32 Zhao B, Hu M. Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells. Oncol Lett 2013; 6 (06) 1749-1755
    CrossrefPubMedSearch in Google Scholar
  • 33 McLaughlin N, Annabi B, Bouzeghrane M, Temme A, Bahary JP, Moumdjian R, Béliveau R. The Survivin-mediated radioresistant phenotype of glioblastoma is regulated by RhoA and inhibited by the green tea polyphenol (−)- epigallocatechin-3-gallate. Brain Res 2006; 1071 (01) 1-9
    CrossrefPubMedSearch in Google Scholar
  • 34 Mukherjee S, Baidoo JN, Sampat S, Mancuso A, David L, Cohen LS, Banerjee P. Liposomal tricurin, a synergistic combination of curcumin, epicatechin gallate and resveratrol, repolarizes tumor-associated microglia/macrophages, and eliminates glioblastoma (GBM) and GBM stem cells. Molecules 2018; 23 (01) 201
    CrossrefPubMedSearch in Google Scholar
  • 35 Taibi A, Bardet MS, Durand Fontanier S, Deluche E, Fredon F, Christou N, Mathonnet M. Managing chemotherapy extravasation in totally implantable central venous access: Use of subcutaneous wash-out technique. J Vasc Access 2020; 21 (05) 723-773
    CrossrefPubMedSearch in Google Scholar
  • 36 Eichenbaum G, Zhou J, De Smedt A, De Jonghe S, Looszova A, Arien T, Goethen FV, Vervoort L, Skukla U, Lammens L. Methods to evaluate and improve the injection site tolerability of intravenous formulations prior to first-in-human testing. J Pharmacol Toxicol Methods 2013; 68 (03) 394-406
    CrossrefPubMedSearch in Google Scholar
  • 37 Pluschnig U, Haslik W, Bartsch R, Mader RM. Extravasation emergencies: State-of-the-art management and progress in clinical research. Memo 2016; 9 (04) 226-230
    CrossrefPubMedSearch in Google Scholar
  • 38 Wang X, Decker CC, Zechner L, Krstin S, Wink M. In vitro wound healing of tumor cells: Inhibition of cell migration by selected cytotoxic alkaloids. BMC Pharmacol Toxicol 2019; 20: 4
    CrossrefPubMedSearch in Google Scholar
  • 39 Salo T, Sutinen M, Hoque Apu E, Sundquist E, Cervigne NK, de Oliveira CE, Akram SU, Ohlmeier S, Suomi F, Eklund L, Juusela P, Åström P, Bitu CC, Santala M, Savolainen K, Korvala K, Leme AFP, Coletta RD. A novel human leiomyoma tissue derived matrix for cell culture studies. BMC Cancer 2015; 15: 981
    CrossrefPubMedSearch in Google Scholar
  • 40 Bradford M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254
    CrossrefPubMedSearch in Google Scholar
  • 41 Pereira DG, Salgado MA, Rocha SC, Santos HL, Villar JA, Contreras RG, Fontes CFL, Barbosa LA, Cortes VF. Involvement of Src signaling in the synergistic effect between cisplatin and digoxin on cancer cell viability. J Cell Biochem 2018; 119 (04) 3352-3362
    CrossrefPubMedSearch in Google Scholar
  • 42 Silva AG, Silva VAO, Oliveira RJS, Rezende AR, Chagas RCR, Lúcia LPS, Romão W, Santos HB, Thomé RG, Reis RM, Ribeiro RIMA. Matteucinol, isolated from Miconia chamissois, induces apoptosis in human glioblastoma lines via the intrinsic pathway and inhibits angiogenesis and tumor growth in vivo. Invest New Drugs 2020; 38(4):1044-1055
    PubMedSearch in Google Scholar
  • 43 Underwood W. AVMA Guidelines for the Euthanasia of Animals: 2013 Edition. Schaumburg, IL: American Veterinary Medical Association; 2013
    Search in Google Scholar