Streptomyces hygroscopicus UFPEDA 3370: A valuable source of the potent cytotoxic agent nigericin and its evaluation against human colorectal cancer cells

被引：5

作者：

Rodini Garcia-Princival, Iza Mirela ^{[1
]}

Princival, Jefferson Luiz ^{[2
]}

da Silva, Emmanuel Dias ^{[2
]}

de Arruda Lima, Sandrine Maria ^{[1
]}

Carregosa, Jhonattas Carvalho ^{[3
]}

Wisniewski Jr, Alberto ^{[3
]}

Oliveira de Lucena, Caio Cezar ^{[1
]}

Halwass, Fernando ^{[2
]}

Alves Franca, Jose Adonias ^{[2
]}

Gomes Rebello Ferreira, Luiz Felipe ^{[4
]}

Hernandes, Marcelo Zaldini ^{[4
]}

Alcantara Saraiva, Karina Lidianne ^{[5
]}

Peixoto, Christina Alves ^{[5
,6
]}

Baratte, Blandine ^{[7
,8
]}

Robert, Thomas ^{[7
,8
]}

Bach, Stephane ^{[7
,8
]}

Gomes, Dayene Correia ^{[9
]}

Guedes Paiva, Patricia Maria ^{[9
]}

Marchand, Pascal ^{[10
]}

Rodrigues, Maria Desterro ^{[1
]}

da Silva, Teresinha Goncalves ^{[1
]}

机构：

[1] Univ Fed Pernambuco, Dept Antibiot, Rua Prof Moraes Rego 1235, BR-50670901 Recife, PE, Brazil

[2] Univ Fed Pernambuco, Dept Quim Fundamental, Av Jornalista Anibal Fernandes S-N, BR-50740560 Recife, PE, Brazil

[3] Univ Fed Sergipe, Dept Quim, Av Marechal Rondon S-N, BR-49100000 Aracaju, Sergipe, Brazil

[4] Univ Fed Pernambuco, Dept Ciencias Farmaceut, Lab Quim Teor Med LQTM, Av Prof Artur de Sa,Cidade Univ, BR-50740521 Recife, PE, Brazil

[5] Fundacao Oswaldo Cruz FIOCRUZ, Lab Ultraestrutura Inst Aggeu Magalhaes IAM, Recife, PE, Brazil

[6] Fundacao Oswaldo Cruz, Inst Ciencias & Tecnol Neuroimunomodulacao INCT N, Inst Oswaldo Cruz, Rio De Janeiro, RJ, Brazil

[7] Sorbonne Univ, Stn Biol Roscoff, Integrat Biol Marine Models Lab LBI2M, CNRS,UMR8227, F-29680 Roscoff, France

[8] Sorbonne Univ, CNRS, FR2424,Stn Biol, Kinase Inhibitor Specialized Screening Facil KISS, F-29688 Roscoff, France

[9] Univ Fed Pernambuco, Dept Bioquim, Rua Prof Moraes Rego SN, BR-50670420 Recife, PE, Brazil

[10] Univ Nantes, Cibles & Medicaments Infect & Canc, IICiMed, EA 1155, F-44000 Nantes, France

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 2021年 / 333卷

关键词：

Autophagy; Natural products; Nigericin; Protein kinases; Apoptosis; LUNG-CARCINOMA; JANUS KINASE; AUTOPHAGY; APOPTOSIS; ANTITUMOR; INHIBITION; CROSSTALK; GSK3-BETA; SURVIVAL; TARGETS;

D O I：

10.1016/j.cbi.2020.109316

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Streptomyces hygroscopicus UFPEDA 3370 was fermented in submerged cultivation and the biomass extract was partitioned, obtaining a fraction purified named EB1. After purification of EB1 fraction, nigericin free acid was obtained and identified. Nigericin presented cytotoxic activity against several cancer cell lines, being most active against HL-60 (human leukemia) and HCT-116 (human colon carcinoma) cell lines, presenting IC50 and (IS) values: 0.0014 mu M, (30.0) and 0.0138 mu M (3.0), respectively. On HCT-116, nigericin caused apoptosis and autophagy. In this study, nigericin was also screened both in vitro and in silico against a panel of cancer-related kinases. Nigericin was able to inhibit both JAK3 and GSK-3 beta kinases in vitro and its binding affinities were mapped through the intermolecular interactions with each target in silico.

引用

页数：11

共 69 条

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