Th1-Biased Immunomodulation and In Vivo Antitumor Effect of a Novel Piperine Analogue
| Autor: | José Maria Barbosa-Filho, Monalisa Taveira Brito, Tatyanna Kelvia Gomes de Sousa, Helivaldo Diógenes da Silva Souza, Jephesson Alex Floriano dos Santos, Rafael Carlos Ferreira, Hemerson Iury Ferreira Magalhães, Tatianne Mota Batista, Normando Alexandre da Silva Costa, Marianna Vieira Sobral, Fagner Carvalho Leite, Vivianne Mendes Mangueira, Ryldene Marques Duarte da Cruz, Bruno F. Lira, Giciane Carvalho Vieira, Petrônio Filgueiras de Athayde-Filho, Robson Cavalcante Veras, Ana Paula Gomes Moura |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Erythrocytes Cell Survival Polyunsaturated Alkamides Helper T lymphocyte Antineoplastic Agents Pharmacology Hemolysis Median lethal dose Article Catalysis Ehrlich ascites carcinoma Immunomodulation Inorganic Chemistry lcsh:Chemistry Mice 03 medical and health sciences chemistry.chemical_compound Alkaloids Piperidines In vivo Acetamides Animals cancer antitumor activity Benzodioxoles Physical and Theoretical Chemistry piperine analogue Carcinoma Ehrlich Tumor Th1-Th2 Balance Molecular Biology lcsh:QH301-705.5 Nitrobenzenes Spectroscopy RAW 264.7 Cells Chemistry Organic Chemistry toxicity General Medicine Acute toxicity Computer Science Applications 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Immune System Piperine Toxicity Female |
| Zdroj: | International Journal of Molecular Sciences, Vol 19, Iss 9, p 2594 (2018) International Journal of Molecular Sciences Volume 19 Issue 9 |
| ISSN: | 1422-0067 |
| Popis: | Natural products have an important role as prototypes in the synthesis of new anticancer drugs. Piperine is an alkaloid amide with antitumor activity and significant toxicity. Then, the N-(p-nitrophenyl)acetamide piperinoate (HE-02) was synthesized, and tested for toxicological and antitumor effects. The toxicity was evaluated in vitro (on RAW 264.7 cells and mice erythrocytes) and in vivo (acute toxicity in mice). The Ehrlich ascites carcinoma model was used to evaluate the antitumor activity of HE-02 (6.25, 12.5 or 25 mg/kg, intraperitoneally, i.p.), as well as toxicity. HE-02 induced only 5.01% of hemolysis, and reduced the viability of RAW 264.7 cells by 49.75% at 1000 µ g/mL. LD50 (lethal dose 50%) was estimated at around 2000 mg/kg (i.p.). HE-02 reduced Ehrlich tumor cell viability and peritumoral microvessels density. There was an increase of Th1 helper T lymphocytes cytokine profile levels (IL-1&beta TNF-&alpha IL-12) and a decrease of Th2 cytokine profile (IL-4, IL-10). Moreover, an increase was observed on reactive oxygen species and nitric oxide production. Weak in vivo toxicological effects were recorded. Our data provide evidence that the piperine analogue HE-02 present low toxicity, and its antitumor effect involves modulation of immune system to a cytotoxic Th1 profile. |
| Databáze: | OpenAIRE |
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