Toxicity and Anti-Proliferative Properties of Ethanol Extract on Cervical Cancer HeLa Cells and Zebrafish Embryos

Overview

Journal Life (Basel)

Specialty Biology

Date 2021 Apr 3

PMID 33804714

Citations 5

Authors

Nguyen T Bich-Loan

Kieu Trung Kien

Nguyen Lai Thanh

Nguyen T Kim-Thanh

Nguyen Quang Huy

Pham The-Hai

Marc Muller

Amandine Nachtergael

Pierre Duez

Nguyen Dinh Thang

Affiliations

Soon will be listed here.

Abstract

In this study, we showed that crude extract of (AI-EtE) expressed its toxicity to HeLa cells with an IC50 dose of 38.8 µg/mL and to zebrafish embryos with malformations, lethality and hatching inhibition at 72-hpf at doses higher than 75 µg/mL. More interestingly, flow cytometry revealed that AI-EtE significantly promoted the number of cells entering apoptotic. Accordingly, the transcript levels of , , and in the cells treated with AI-EtE at IC50 dose were 1.55-, 1.62-, and 2.45-fold higher than those in the control cells, respectively. Moreover, treatment with AI-EtE caused cell cycle arrest at the G1 phase in a p53-independent manner. Particularly, percentages of AI-EtE-treated cells in G1, S, G2/M were, respectively 85%, 6.7% and 6.4%; while percentages of control cells in G1, S, G2/M were 64%, 15% and 19%, respectively. Consistent with cell cycle arrest, the expressions of and in AI-EtE-treated cells were up-regulated 1.9- and 1.64-fold, respectively. Significantly, treatment with AI-EtE also decreased anchorage-independent growth of HeLa cells. In conclusion, we suggest that can be considered as a medicinal plant with a possible use against cervical cancer cells; however, the used dose should be carefully monitored, especially when applying to pregnant women.

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References

Cavalcante G, Schaan A, Fonseca Cabral G, Santana-da-Silva M, Pinto P, Vidal A . A Cell's Fate: An Overview of the Molecular Biology and Genetics of Apoptosis. Int J Mol Sci. 2019; 20(17). PMC: 6747454. DOI: 10.3390/ijms20174133. View

Hou Y, Wu M, Hwang Y, Chang F, Wu Y, Wu C . The natural diterpenoid ovatodiolide induces cell cycle arrest and apoptosis in human oral squamous cell carcinoma Ca9-22 cells. Life Sci. 2009; 85(1-2):26-32. DOI: 10.1016/j.lfs.2009.04.013. View

Lawson N, Weinstein B . In vivo imaging of embryonic vascular development using transgenic zebrafish. Dev Biol. 2002; 248(2):307-18. DOI: 10.1006/dbio.2002.0711. View

Lanni J, Lowe S, Licitra E, Liu J, Jacks T . p53-independent apoptosis induced by paclitaxel through an indirect mechanism. Proc Natl Acad Sci U S A. 1997; 94(18):9679-83. PMC: 23249. DOI: 10.1073/pnas.94.18.9679. View

Ohtsubo M, Theodoras A, Schumacher J, Roberts J, Pagano M . Human cyclin E, a nuclear protein essential for the G1-to-S phase transition. Mol Cell Biol. 1995; 15(5):2612-24. PMC: 230491. DOI: 10.1128/MCB.15.5.2612. View

Yao J, He H, Xue J, Wang J, Jin H, Wu J . Mori Ramulus (Chin.Ph.)-the Dried Twigs of L./Part 1: Discovery of Two Novel Coumarin Glycosides from the Anti-Hyperuricemic Ethanol Extract. Molecules. 2019; 24(3). PMC: 6384676. DOI: 10.3390/molecules24030629. View

Arellano M, Moreno S . Regulation of CDK/cyclin complexes during the cell cycle. Int J Biochem Cell Biol. 1997; 29(4):559-73. DOI: 10.1016/s1357-2725(96)00178-1. View

Levine A . p53, the cellular gatekeeper for growth and division. Cell. 1997; 88(3):323-31. DOI: 10.1016/s0092-8674(00)81871-1. View

Cragg G, Newman D . Natural products: a continuing source of novel drug leads. Biochim Biophys Acta. 2013; 1830(6):3670-95. PMC: 3672862. DOI: 10.1016/j.bbagen.2013.02.008. View

10.

Ho C, Lin R, Zhu W, Wen T, Hu C, Lee Y . Transcription-independent and -dependent p53-mediated apoptosis in response to genotoxic and non-genotoxic stress. Cell Death Discov. 2019; 5:131. PMC: 6711993. DOI: 10.1038/s41420-019-0211-5. View

11.

Kohler D, Goldspiel B . Paclitaxel (taxol). Pharmacotherapy. 1994; 14(1):3-34. DOI: 10.1002/j.1875-9114.1994.tb02785.x. View

12.

Razafindrakoto Z, Donno D, Tombozara N, Andriamaniraka H, Andrianjara C, Ramanitrahasimbola D . Antioxidant, Anti-Inflammatory, and Antidiabetic Activities of Leaves and Stems of Uapaca bojeri Bail. (EUPHORBIACEAE), an Endemic Plant of Madagascar. Pharmaceuticals (Basel). 2020; 13(4). PMC: 7243096. DOI: 10.3390/ph13040071. View

13.

Newman D, Cragg G . Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod. 2012; 75(3):311-35. PMC: 3721181. DOI: 10.1021/np200906s. View

14.

Ohgami N, Yamanoshita O, Thang N, Yajima I, Nakano C, Wenting W . Carcinogenic risk of chromium, copper and arsenic in CCA-treated wood. Environ Pollut. 2015; 206:456-60. DOI: 10.1016/j.envpol.2015.07.041. View

15.

Schutte B, Nuydens R, Geerts H, Ramaekers F . Annexin V binding assay as a tool to measure apoptosis in differentiated neuronal cells. J Neurosci Methods. 1999; 86(1):63-9. DOI: 10.1016/s0165-0270(98)00147-2. View

16.

Elmore S . Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007; 35(4):495-516. PMC: 2117903. DOI: 10.1080/01926230701320337. View

17.

Wijesundara N, Rupasinghe H . Bactericidal and Anti-Biofilm Activity of Ethanol Extracts Derived from Selected Medicinal Plants against . Molecules. 2019; 24(6). PMC: 6471238. DOI: 10.3390/molecules24061165. View

18.

Li Z, Zhao J, Du Y, Park H, Sun S, Bernal-Mizrachi L . Down-regulation of 14-3-3zeta suppresses anchorage-independent growth of lung cancer cells through anoikis activation. Proc Natl Acad Sci U S A. 2007; 105(1):162-7. PMC: 2224179. DOI: 10.1073/pnas.0710905105. View

19.

Darzynkiewicz Z, Huang X, Zhao H . Analysis of Cellular DNA Content by Flow Cytometry. Curr Protoc Cytom. 2017; 82:7.5.1-7.5.20. DOI: 10.1002/cpcy.28. View

20.

Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55-63. DOI: 10.1016/0022-1759(83)90303-4. View