Rosália Maria Tôrres de Lima1, Antonielly Campinho Dos Reis2, José Victor de Oliveira Santos1, José Roberto de Oliveira Ferreira3, José Williams Gomes de Oliveira Filho1, Ana Carolina Soares Dias4, Ag-Anne Pereira Melo de Menezes1, Ana Maria Oliveira Ferreira da Mata1, Marcus Vinícius Oliveira Barros de Alencar2, Teresinha de Jesus Aguiar Dos Santos Andrade5, Márcia Fernanda Correia Jardim Paz1, Débora Caroline do Nascimento Rodrigues6, Paulo Michel Pinheiro Ferreira7, João Marcelo de Castro E Sousa8, Siddhartha Kumar Mishra9, Muhammad Torequl Islam10, Ana Amélia de Carvalho Melo-Cavalcante8. 1. Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Piauí, 64,049-550, Brazil. 2. Laboratory of Genetical Toxicology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Piauí, 64,049-550, Brazil. 3. Nucleus of Biological Sciences (NUCIB), State University of Health Sciences of Alagoas, Maceió, Alagoas, 57010-382, Brazil. 4. Laboratory of Genetics and Molecular Biology, Federal University of Maranhão, Bacanga, São Luís, Maranhão, 65,080-805, Brazil. 5. Nucleus of Applied Research to Sciences (NIAC), Federal Institute of Education, Science and Technology of Maranhão (IFMA), São Luís, MA, 65075-441, Brazil. 6. Laboratory of Experimental Cancerology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Piauí, 64,049-550, Brazil. 7. Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Piauí, 64,049-550, Brazil; Laboratory of Experimental Cancerology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Piauí, 64,049-550, Brazil. 8. Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Piauí, 64,049-550, Brazil; Laboratory of Genetical Toxicology, Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Piauí, 64,049-550, Brazil. 9. Cancer Biology Laboratory, School of Biological Sciences (Zoology), Dr. Harisingh Gour Central University, Sagar, 470003, M.P., India. Electronic address: siddharthakm@yahoo.com. 10. Laboratory of Theoretical and Computational Biophysics, Ton Duc Thang University, Ho Chi Minh City, 700000, Viet Nam; Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, 700000, Viet Nam. Electronic address: muhammad.torequl.islam@tdtu.edu.vn.
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.
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.