Acetogenins-Rich Fractions of Suppress Human Glioblastoma Viability and Migration by Regulating Necroptosis and MMP-2 Activity In Vitro

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 May 13

PMID 37175219

Authors

Lorena R Sousa

Ana Gabriela S Oliveira

Antonio Arantes

Joao Gabriel M Junqueira

Gerso P Alexandre

Vanessa G P Severino

Rui Manuel Reis

Bonglee Kim

Rosy I M A Ribeiro

Affiliations

Soon will be listed here.

Abstract

Glioblastoma (GBM) is an incurable primary brain tumor with a poor prognosis. Resection, radiation therapy, and temozolomide (TMZ) are insufficient to increase survival, making the treatment limited. Thus, the search for more effective and specific treatments is essential, making plants a promising source for elucidating new anti-glioblastoma compounds. Accordingly, this study investigated the effects of four fractions of hexane and ethyl acetate extract of Mart., enriched with acetogenins, against GBM cell lines. All four fractions were selectively cytotoxic to GBM cells when compared to TMZ. Moreover, fractions delayed cell migration; reduced cytoplasmic projections, the metalloproteinase 2 (MMP-2) activity; and induced morphological changes characteristic of necroptosis, possibly correlated with the increase in receptor-interacting protein kinase 1 and 3 (RIP-1 and RIP-3), apoptosis-inducing factor (AIF), and the non-activation of cleaved caspase 8. The present findings reinforce that fractions of Mart. should be considered for more studies focusing treatment of GBM.

Citing Articles

Encapsulated LyeTx III Peptide: Cytotoxic Agent Isolated from Spider Venom.

Santos D, Santiago L, Santos N, Romao W, Resende J, De Lima M Toxins (Basel). 2025; 17(1).

PMID: 39852985 PMC: 11768708. DOI: 10.3390/toxins17010032.

References

de Pedro N, Cautain B, Melguizo A, Vicente F, Genilloud O, Pelaez F . Mitochondrial complex I inhibitors, acetogenins, induce HepG2 cell death through the induction of the complete apoptotic mitochondrial pathway. J Bioenerg Biomembr. 2012; 45(1-2):153-64. DOI: 10.1007/s10863-012-9489-1. View

Han B, Wang T, Shen S, Yu Y, Mao C, Yao Z . Annonaceous acetogenin mimic AA005 induces cancer cell death via apoptosis inducing factor through a caspase-3-independent mechanism. BMC Cancer. 2015; 15:139. PMC: 4379763. DOI: 10.1186/s12885-015-1133-0. View

Gutierrez M, Duran A, Mejias F, Molinillo J, Megias D, Valdivia M . Bio-Guided Isolation of Acetogenins from Deciduous Leaves: Production of Nanocarriers to Boost the Bioavailability Properties. Molecules. 2020; 25(20). PMC: 7587976. DOI: 10.3390/molecules25204861. View

Wu F, Zhao G, Zeng L, Zhang Y, Schwedler J, McLaughlin J . Additional bioactive acetogenins, annomutacin and (2,4-trans and cis)-10R-annonacin-A-ones, from the leaves of Annona muricata. J Nat Prod. 1995; 58(9):1430-7. DOI: 10.1021/np50123a015. View

Zhao G, Rieser M, Hui Y, Miesbauer L, Smith D, McLaughlin J . Biologically active acetogenins from stem bark of Asimina triloba. Phytochemistry. 1993; 33(5):1065-73. DOI: 10.1016/0031-9422(93)85024-l. View

Rajesh Y, Banerjee A, Pal I, Biswas A, Das S, Dey K . Delineation of crosstalk between HSP27 and MMP-2/MMP-9: A synergistic therapeutic avenue for glioblastoma management. Biochim Biophys Acta Gen Subj. 2019; 1863(7):1196-1209. DOI: 10.1016/j.bbagen.2019.04.015. View

Li Y, Ye J, Chen Z, Wen J, Li F, Su P . Annonaceous acetogenins mediated up-regulation of Notch2 exerts growth inhibition in human gastric cancer cells in vitro. Oncotarget. 2017; 8(13):21140-21152. PMC: 5400572. DOI: 10.18632/oncotarget.15502. View

Lee Y, Park K, Nam H, Cho M, Lee S . Apigenin causes necroptosis by inducing ROS accumulation, mitochondrial dysfunction, and ATP depletion in malignant mesothelioma cells. Korean J Physiol Pharmacol. 2020; 24(6):493-502. PMC: 7585594. DOI: 10.4196/kjpp.2020.24.6.493. View

Costa E, Pinheiro M, Xavier C, Silva J, Amaral A, Souza A . A pyrimidine-beta-carboline and other alkaloids from Annona foetida with antileishmanial activity. J Nat Prod. 2006; 69(2):292-4. DOI: 10.1021/np050422s. View

10.

Kim E, Tian F, Woo M . Asitrocin, (2,4)-cis- and trans-asitrocinones: novel bioactive mono-tetrahydrofuran acetogenins from Asimina triloba seeds. J Nat Prod. 2000; 63(11):1503-6. DOI: 10.1021/np000180q. View

11.

Liaw C, Chang F, Wu C, Chen S, Bastow K, Hayashi K . Nine new cytotoxic monotetrahydrofuranic Annonaceous acetogenins from Annona montana. Planta Med. 2004; 70(10):948-59. DOI: 10.1055/s-2004-832622. View

12.

Ismail N, Ismail M, Imam M, Azmi N, Fathy S, Foo J . Mechanistic basis for protection of differentiated SH-SY5Y cells by oryzanol-rich fraction against hydrogen peroxide-induced neurotoxicity. BMC Complement Altern Med. 2014; 14:467. PMC: 4528700. DOI: 10.1186/1472-6882-14-467. View

13.

Yiallouris A, Patrikios I, Johnson E, Sereti E, Dimas K, De Ford C . Annonacin promotes selective cancer cell death via NKA-dependent and SERCA-dependent pathways. Cell Death Dis. 2018; 9(7):764. PMC: 6037677. DOI: 10.1038/s41419-018-0772-x. View

14.

Bermejo A, Figadere B, Zafra-Polo M, Barrachina I, Estornell E, Cortes D . Acetogenins from Annonaceae: recent progress in isolation, synthesis and mechanisms of action. Nat Prod Rep. 2005; 22(2):269-303. DOI: 10.1039/b500186m. View

15.

Woo M, Kim D, McLaughlin J . Asitrilobins A and B: cytotoxic mono-THF annonaceous acetogenins from the seeds of Asimina triloba. Phytochemistry. 1999; 50(6):1033-40. DOI: 10.1016/s0031-9422(98)00632-3. View

16.

Torres M, Rachagani S, Purohit V, Pandey P, Joshi S, Moore E . Graviola: a novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism. Cancer Lett. 2012; 323(1):29-40. PMC: 3371140. DOI: 10.1016/j.canlet.2012.03.031. View

17.

Belizario J, Vieira-Cordeiro L, Enns S . Necroptotic Cell Death Signaling and Execution Pathway: Lessons from Knockout Mice. Mediators Inflamm. 2015; 2015:128076. PMC: 4600508. DOI: 10.1155/2015/128076. View

18.

Mangal M, Khan M, Agarwal S . Acetogenins as Potential Anticancer Agents. Anticancer Agents Med Chem. 2015; 16(2):138-59. DOI: 10.2174/1871520615666150629101827. View

19.

Itharat A, Houghton P, Eno-Amooquaye E, Burke P, Sampson J, Raman A . In vitro cytotoxic activity of Thai medicinal plants used traditionally to treat cancer. J Ethnopharmacol. 2003; 90(1):33-8. DOI: 10.1016/j.jep.2003.09.014. View

20.

Tantithanaporn S, Wattanapiromsakul C, Itharat A, Keawpradub N . Cytotoxic activity of acetogenins and styryl lactones isolated from Goniothalamus undulatus Ridl. root extracts against a lung cancer cell line (COR-L23). Phytomedicine. 2010; 18(6):486-90. DOI: 10.1016/j.phymed.2010.10.010. View