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

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.

SUBMITTER: Santos J

PROVIDER: S-EPMC6165130 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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

Santos Jephesson J Brito Monalisa M Ferreira Rafael R Moura Ana Paula AP Sousa Tatyanna T Batista Tatianne T Mangueira Vivianne V Leite Fagner F Cruz Ryldene R Vieira Giciane G Lira Bruno B Athayde-Filho Petrônio P Souza Helivaldo H Costa Normando N Veras Robson R Barbosa-Filho José Maria JM Magalhães Hemerson H Sobral Marianna M

International journal of molecular sciences 20180901 9

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 <i>N</i>-(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 act ...[more]

PMID: 30200386

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

Publications

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

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