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Int. J. Mol. Sci. 2018, 19(9), 2594; https://doi.org/10.3390/ijms19092594

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

1
Programa de Pós Graduação em Produtos Naturais e Sintéticos Bioativos, Universidade Federal da Paraíba, 58051-970 João Pessoa, Paraíba, Brazil
2
Departamento de Morfologia, Universidade Federal da Paraíba, 58051-970 João Pessoa, Paraíba, Brazil
3
Departamento de Química, Universidade Federal da Paraíba, 58051-970 João Pessoa, Paraíba, Brazil
4
Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, 58051-970 João Pessoa, Paraíba, Brazil
*
Author to whom correspondence should be addressed.
Received: 16 July 2018 / Revised: 10 August 2018 / Accepted: 14 August 2018 / Published: 1 September 2018
(This article belongs to the Special Issue Natural Bioactives and Phytochemicals in Cancer Prevention)
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Abstract

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. View Full-Text
Keywords: cancer; piperine analogue; antitumor activity; toxicity cancer; piperine analogue; antitumor activity; toxicity
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Santos, J.; Brito, M.; Ferreira, R.; Moura, A.P.; Sousa, T.; Batista, T.; Mangueira, V.; Leite, F.; Cruz, R.; Vieira, G.; Lira, B.; Athayde-Filho, P.; Souza, H.; Costa, N.; Veras, R.; Barbosa-Filho, J.M.; Magalhães, H.; Sobral, M. Th1-Biased Immunomodulation and In Vivo Antitumor Effect of a Novel Piperine Analogue. Int. J. Mol. Sci. 2018, 19, 2594.

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