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Antitumoral effects of [6]-gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] in sarcoma 180 cells through cytogenetic mechanisms - 19/04/20

Doi : 10.1016/j.biopha.2020.110004 
Rosália Maria Tôrres de Lima a, Antonielly Campinho dos Reis b, José Victor de Oliveira Santos a, José Roberto de Oliveira Ferreira c, José Williams Gomes de Oliveira Filho a, Ana Carolina Soares Dias d, Ag-Anne Pereira Melo de Menezes a, Ana Maria Oliveira Ferreira da Mata a, Marcus Vinícius Oliveira Barros de Alencar b, Teresinha de Jesus Aguiar dos Santos Andrade e, Márcia Fernanda Correia Jardim Paz a, Débora Caroline do Nascimento Rodrigues f, Paulo Michel Pinheiro Ferreira a, f, João Marcelo de Castro e Sousa a, b, Siddhartha Kumar Mishra g, , Muhammad Torequl Islam h, i, , Ana Amélia de Carvalho Melo-Cavalcante a, b
a Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Piauí, 64,049-550, Brazil 
b Laboratory of Genetical Toxicology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Piauí, 64,049-550, Brazil 
c Nucleus of Biological Sciences (NUCIB), State University of Health Sciences of Alagoas, Maceió, Alagoas, 57010-382, Brazil 
d Laboratory of Genetics and Molecular Biology, Federal University of Maranhão, Bacanga, São Luís, Maranhão, 65,080-805, Brazil 
e Nucleus of Applied Research to Sciences (NIAC), Federal Institute of Education, Science and Technology of Maranhão (IFMA), São Luís, MA, 65075-441, Brazil 
f Laboratory of Experimental Cancerology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Piauí, 64,049-550, Brazil 
g Cancer Biology Laboratory, School of Biological Sciences (Zoology), Dr. Harisingh Gour Central University, Sagar, 470003, M.P., India 
h Laboratory of Theoretical and Computational Biophysics, Ton Duc Thang University, Ho Chi Minh City, 700000, Viet Nam 
i Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, 700000, Viet Nam 

Corresponding author at: Cancer Biology Laboratory, School of Biological Sciences (Zoology), Dr. Harisingh Gour Central University, Sagar, 470003, M.P., India.Cancer Biology LaboratorySchool of Biological Sciences (Zoology)Dr. Harisingh Gour Central UniversitySagarM.P.470003India⁎⁎Corresponding author at: Laboratory of Theoretical and Computational Biophysics, & Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City-700000, Viet Nam.Laboratory of Theoretical and Computational Biophysics, & Faculty of PharmacyTon Duc Thang UniversityHo Chi Minh City700000Viet Nam

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Highlights

[6]-Gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] is a phenolic substance with several pharmacological properties.
[6]-Gingerol showed antitumoral effects in primary cells of Sarcoma 180 as well as in peripheral blood lymphocytes of mice.
[6]-Gingerol induced cytogenetic changes in S-180 cells, biomarkers of genotoxicity, mutagenicity, apoptosis and necrosis.
[6]-Gingerol may be an antitumoral agent with mechanisms associated with reducing genetic instability inducing apoptosis.

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Abstract

Background

[6]-Gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] is a phenolic substance reported for several ethnopharmacological usage by virtue of its antioxidant, antiemetic, anti-inflammatory and anticancer properties. This study assessed the antitumoral effects of [6]-Gingerol in primary cells of Sarcoma 180 as well as in peripheral blood lymphocytes of mice.

Methods

The effect of [6]-Gingerol was assessed by applying cytogenetic biomarkers as indicative of genotoxicity, mutagenicity and apoptosis. Ascitic liquid cells were treated with [6]-Gingerol at concentrations of 21.33, 42.66 and 85.33 μM and subjected to the cytotoxicity assays using Trypan blue test and the comet assay, as well as the cytokinesis-block micronucleus assay. Doxorubicin (6 μM) and hydrogen peroxide (85.33 μM) were used as positive controls.

Results

[6]-Gingerol, especially at concentrations of 42.66 and 85.33 μM, showed notable cytotoxicity in Sarcoma 180 cells by reducing cell viability and cell division rates via induction of apoptosis. Genotoxicity at the concentrations used was punctuated by the increase in the index and frequency of DNA damage in tested groups. [6]-Gingerol, at all concentrations tested, did not induce significant aneugenic and/or clastogenic effects. It did, however, induced other nuclear abnormalities, such as nucleoplasmic bridges, nuclear buds and apoptosis. The genotoxic effects observed in the cotreatment with H2O2 (challenge assay) employing neoplastic and healthy cells, indicated that [6]-Gingerol may induce oxidative stress.

Conclusions

Observations suggest that [6]-Gingerol may be a candidate for pharmaceutical antitumoral formulations due to its cytotoxicity and to mechanisms associated with genetic instability generated by nuclear alterations especially by apoptosis.

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Keywords : [6]-Gingerol, Sarcoma 180, Genotoxicity, Apoptosis, DNA damage


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