Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2019 Nov 6

PMID 31683835

Citations 6

Authors

Izabela N Faria Gomes

Renato J Silva-Oliveira

Viviane A Oliveira Silva

Marcela N Rosa

Patrik S Vital

Maria Cristina S Barbosa

Fabio Vieira dos Santos

Joao Gabriel M Junqueira

Vanessa G P Severino

Bruno G Oliveira

Wanderson Romao

Rui Manuel Reis

Rosy Iara Maciel de Azambuja Ribeiro

Affiliations

Soon will be listed here.

Abstract

Plant-based compounds are an option to explore and perhaps overcome the limitations of current antitumor treatments. Mart. is a plant with a broad spectrum of biological activities, but its antitumor activity is still unclear. The purpose of our study was to determine the effects of fractions on a panel of cervical cancer cell lines and a normal keratinocyte cell line. The antitumor effect was investigated in vitro by viability assays, cell cycle, apoptosis, migration, and invasion assays. Intracellular signaling was assessed by Western blot, and major compounds were identified by mass spectrometry. All fractions exhibited a cytotoxic effect on cisplatin-resistant cell lines, SiHa and HeLa. C3 and C5 were significantly more cytotoxic and selective than cisplatin in SiHa and Hela cells. However, in CaSki, a cisplatin-sensitive cell line, the compounds did not demonstrate higher cytotoxicity when compared with cisplatin. Alkaloids and acetogenins were the main compounds identified in the fractions. These fractions also markedly decreased cell proliferation with p21 increase and cell cycle arrest in G2/M. These effects were accompanied by an increase of H2AX phosphorylation levels and DNA damage index. In addition, fractions C3 and C5 promoted p62 accumulation and decrease of LC3II, as well as acid vesicle levels, indicating the inhibition of autophagic flow. These findings suggest that fractions may become effective antineoplastic drugs and highlight the autophagy inhibition properties of these fractions in sensitizing cervical cancer cells to treatment.

Citing Articles

Laherradurin Inhibits Colorectal Cancer Cell Growth by Induction of Mitochondrial Dysfunction and Autophagy Induction.

Delgado-Waldo I, Dokudovskaya S, Loissell-Baltazar Y, Perez-Arteaga E, Coronel-Hernandez J, Martinez-Vazquez M Cells. 2024; 13(19.

PMID: 39404412 PMC: 11475353. DOI: 10.3390/cells13191649.

LCMS/MS Phytochemical Profiling, Molecular, Pathological, and Immune-Histochemical Studies on the Anticancer Properties of .

Abdallah R, Al-Saleem M, Abdel-Mageed W, Al-Attar A, Shehata Y, Abdel-Fattah D Molecules. 2023; 28(15).

PMID: 37570713 PMC: 10421100. DOI: 10.3390/molecules28155744.

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

Sousa L, Oliveira A, Arantes A, Junqueira J, Alexandre G, Severino V Molecules. 2023; 28(9).

PMID: 37175219 PMC: 10179884. DOI: 10.3390/molecules28093809.

Porric acid E, a natural compound from Rhytidhysteron sp. BZM-9, suppresses colorectal cancer growth via an autophagy-dependent pathway.

Tang D, Zhang W, Zou Z, Wang Y, Yan S, Zhang S J Cancer. 2022; 13(14):3554-3565.

PMID: 36484011 PMC: 9723991. DOI: 10.7150/jca.77588.

Bioprospecting of Natural Compounds from Brazilian Cerrado Biome Plants in Human Cervical Cancer Cell Lines.

Rosa M, E Silva L, Longato G, Evangelista A, Gomes I, Alves A Int J Mol Sci. 2021; 22(7).

PMID: 33806119 PMC: 8036847. DOI: 10.3390/ijms22073383.

References

Ye Q, He K, Oberlies N, Zeng L, Shi G, Evert D . Longimicins A-D: novel bioactive acetogenins from Asimina longifolia (annonaceae) and structure-activity relationships of asimicin type of annonaceous acetogenins. J Med Chem. 1996; 39(9):1790-6. DOI: 10.1021/jm9600510. View

Singh S, Vats S, Chia A, Tan T, Deng S, Ong M . Dual role of autophagy in hallmarks of cancer. Oncogene. 2017; 37(9):1142-1158. DOI: 10.1038/s41388-017-0046-6. View

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

Meneses da Silva E, Roblot F, Mahuteau J, Cave A . Coriadienin, the first annonaceous acetogenin with two double bonds isolated from Annona coriaceae. J Nat Prod. 1996; 59(5):528-30. DOI: 10.1021/np960079e. View

de Pedro N, Cautain B, Melguizo A, Cortes D, Vicente F, Genilloud O . Analysis of cytotoxic activity at short incubation times reveals profound differences among Annonaceus acetogenins, inhibitors of mitochondrial Complex I. J Bioenerg Biomembr. 2012; 45(1-2):145-52. DOI: 10.1007/s10863-012-9490-8. View

Broustas C, Lieberman H . DNA damage response genes and the development of cancer metastasis. Radiat Res. 2014; 181(2):111-30. PMC: 4064942. DOI: 10.1667/RR13515.1. View

Newman D, Cragg G . Natural Products as Sources of New Drugs from 1981 to 2014. J Nat Prod. 2016; 79(3):629-61. DOI: 10.1021/acs.jnatprod.5b01055. View

Chen K, Shou L, Lin F, Duan W, Wu M, Xie X . Artesunate induces G2/M cell cycle arrest through autophagy induction in breast cancer cells. Anticancer Drugs. 2014; 25(6):652-62. DOI: 10.1097/CAD.0000000000000089. View

Liu Y, Liu D, Wan W, Zhang H . In vitro mitochondria-mediated anticancer and antiproliferative effects of Annona glabra leaf extract against human leukemia cells. J Photochem Photobiol B. 2018; 189:29-35. DOI: 10.1016/j.jphotobiol.2018.07.026. View

10.

Silva-Oliveira R, Silva V, Martinho O, Cruvinel-Carloni A, Melendez M, Rosa M . Cytotoxicity of allitinib, an irreversible anti-EGFR agent, in a large panel of human cancer-derived cell lines: KRAS mutation status as a predictive biomarker. Cell Oncol (Dordr). 2016; 39(3):253-63. DOI: 10.1007/s13402-016-0270-z. View

11.

Mead T, Lefebvre V . Proliferation assays (BrdU and EdU) on skeletal tissue sections. Methods Mol Biol. 2014; 1130:233-243. PMC: 4074019. DOI: 10.1007/978-1-62703-989-5_17. View

12.

Silva-Oliveira R, Melendez M, Martinho O, Zanon M, de Souza Viana L, Carvalho A . AKT can modulate the response of HNSCC cells to irreversible EGFR inhibitors. Oncotarget. 2017; 8(32):53288-53301. PMC: 5581110. DOI: 10.18632/oncotarget.18395. View

13.

Kielbik M, Krzyzanowski D, Pawlik B, Klink M . Cisplatin-induced ERK1/2 activity promotes G1 to S phase progression which leads to chemoresistance of ovarian cancer cells. Oncotarget. 2018; 9(28):19847-19860. PMC: 5929431. DOI: 10.18632/oncotarget.24884. View

14.

Geissmann Q . OpenCFU, a new free and open-source software to count cell colonies and other circular objects. PLoS One. 2013; 8(2):e54072. PMC: 3574151. DOI: 10.1371/journal.pone.0054072. View

15.

Vamanu E . Antioxidant properties of mushroom mycelia obtained by batch cultivation and tocopherol content affected by extraction procedures. Biomed Res Int. 2014; 2014:974804. PMC: 4119741. DOI: 10.1155/2014/974804. View

16.

Visagie M, Joubert A . In vitro effects of 2-methoxyestradiol-bis-sulphamate on reactive oxygen species and possible apoptosis induction in a breast adenocarcinoma cell line. Cancer Cell Int. 2011; 11(1):43. PMC: 3251537. DOI: 10.1186/1475-2867-11-43. View

17.

Chen Y, Chen Y, Shi Y, Ma C, Wang X, Li Y . Antitumor activity of Annona squamosa seed oil. J Ethnopharmacol. 2016; 193:362-367. DOI: 10.1016/j.jep.2016.08.036. View

18.

Rashmi R, DeSelm C, Helms C, Bowcock A, Rogers B, Rader J . AKT inhibitors promote cell death in cervical cancer through disruption of mTOR signaling and glucose uptake. PLoS One. 2014; 9(4):e92948. PMC: 3976291. DOI: 10.1371/journal.pone.0092948. View

19.

Liaw C, Chang F, Lin C, Chou C, Chiu H, Wu M . New cytotoxic monotetrahydrofuran annonaceous acetogenins from Annona muricata. J Nat Prod. 2002; 65(4):470-5. DOI: 10.1021/np0105578. View

20.

Yu J, Li T, Sun L, Luo X, Ding W, Li D . [Studies on the chemical constituents of the seeds from Artabostrys hexapetalus (Annonaceae)]. Yao Xue Xue Bao. 2003; 36(4):281-6. View