Th1-Biased Immunomodulation and In Vivo Antitumor Effect of a Novel Piperine Analogue

International Journal of Molecular Sciences

Giciane Vieira¹  Normando Costa²  Petrônio Athayde-Filho²  Helivaldo Souza²  Bruno Lira²  Ryldene Cruz³  Robson Veras³  JoséMaria Barbosa-Filho³  Tatyanna Sousa³  Jephesson Santos³  Marianna Sobral³  Tatianne Batista³  Fagner Leite³  AnaPaula Moura³  Vivianne Mangueira³  Monalisa Brito³  Hemerson Magalhães³  Rafael Ferreira³ 

[1] Departamento de Morfologia, Universidade Federal da Paraíba, 58051-970 João Pessoa, Paraíba, Brazil;Departamento de Química, Universidade Federal da Paraíba, 58051-970 João Pessoa, Paraíba, Brazil;Programa de Pós Graduação em Produtos Naturais e Sintéticos Bioativos, Universidade Federal da Paraíba, 58051-970 João Pessoa, Paraíba, Brazil;

关键词: cancer;    piperine analogue;    antitumor activity;    toxicity;   

DOI  :  10.3390/ijms19092594

来源: DOAJ

【 摘 要 】

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 µg/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-1β, TNF-α, 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.

【 授权许可】

Unknown