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

Santos, Jephesson A.F.; Brito, Monalisa Taveira; Ferreira, Rafael Carlos; Moura, Ana Paula Gomes e; Sousa, Tatyanna Kélvia Gomes de; Batista, Tatianne Mota; Mangueira, Vivianne Mendes; Leite, Fagner Carvalho; Cruz, Ryldene Marques Duarte da; Vieira, Giciane Carvalho; Lira, Bruno Freitas; Athayde-Filho, Petrônio Filgueiras de; Souza, Helivaldo Diógenes da Silva; Costa, Normando; Veras, Robson Cavalcante; Barbosa-Filho, José Maria; Magalhães, Hemerson Iury Ferreira; Sobral, Marianna Vieira

doi:10.3390/ijms19092594

Cited by 22 publications

(19 citation statements)

References 60 publications

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“…Similarly, piperine exhibited positive effects against cadmium‐induced oxidative stress in cultured human peripheral blood lymphocytes (Verma, Bal, Gupta, Aggarwal, & Yadav, 2018). Furthermore, research by Santos and coworkers showed that the piperine analogue, N‐( p ‐nitrophenyl)acetamide piperinoate, exhibits low toxicity and shows antitumor effects by Th1‐based immunomodulation (Santos et al, 2018). Moreover, Kumar et al (2015) indicated that piperine enhances antioxidant function by prevention of glutathione depletion and restoration of cytokine levels.…”

Section: Health Perspectivesmentioning

confidence: 99%

Piperine: A review of its biological effects

Haq

Imran

Nadeem

et al. 2020

Phytotherapy Research

232

106

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Medicinal plants have been used for years as a source of food, spices, and, in traditional medicine, as a remedy to numerous diseases. Piper nigrum, belonging to the family Piperaceae is one of the most widely used spices all over the world. It has a distinct sharp flavor attributed to the presence of the phytochemical, piperine. Apart from its use as a spice, P. nigrum is frequently used for medicinal, preservation, and perfumery purposes. Black pepper contains 2–7.4% of piperine, varying in content is associated with the pepper plant. Piperine displays numerous pharmacological effects such as antiproliferative, antitumor, antiangiogenesis, antioxidant, antidiabetic, anti‐obesity, cardioprotective, antimicrobial, antiaging, and immunomodulatory effects in various in vitro and in vivo experimental trials. Furthermore, piperine has also been documented for its hepatoprotective, anti‐allergic, anti‐inflammatory, and neuroprotective properties. This review highlights and discusses the medicinal and health‐promoting effects of piperine, along with possible mechanisms of its action in health promotion and disease prevention. In addition, the present review summarizes the recent literature related to piperine as a therapeutic agent against several diseases.

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Section: Health Perspectivesmentioning

confidence: 99%

Piperine: A review of its biological effects

Haq

Imran

Nadeem

et al. 2020

Phytotherapy Research

232

106

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“…Then, the AMTAC-17 effect on microvessels density may be dependent on IL-12 antiangiogenic action. Additionally, IL-12, IL-1β, and TNF-α represent the Th1 cytokines profile, which is known for the cytotoxic effect against cancer cells [22,23]. This effect involves macrophage activation to secrete proinflammatory cytokines and produce reactive oxygen species and nitric oxide [24].…”

Section: Biological Evaluationmentioning

confidence: 99%

“…Cells from ascitic fluid (1 × 10 6 cells) of the tumor control, 12.5 mg/kg AMTAC-17, and 25 mg/kg 5-FU groups were harvested, gently fixed by using 70% ice-cold ethanol, and frozen overnight (−20 • C). Samples were harvested by centrifugation (400× g, 10 min), and then incubated with RNAse (0.1 mg/mL) and propidium iodide (PI) (0.05 mg/mL) (Sigma Aldrich, St. Louis, MO, USA) (37 • C, 30 min) [22] with modifications. The DNA content was analyzed by flow cytometry (BD FACSCantoTM II, Woburn, MA, USA) and 10,000 events were acquired.…”

Section: Cell Cycle Analysesmentioning

confidence: 99%

Antitumor Effect of a Novel Spiro-Acridine Compound is Associated with Up-Regulation of Th1-Type Responses and Antiangiogenic Action

et al. 2019

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Tumor cells have specific features, including angiogenesis induction, cell cycle dysregulation, and immune destruction evasion. By inducing a T helper type 2 (Th2) immune response, tumor cells may favor immune tolerance within the tumor, which allows progression of cancer growth. Drugs with potential antitumor activity are the spiro-acridines, which is a promising new class of acridine compounds. Herein, the novel spiro-acridine (E)-5 -oxo-1 -((3,4,5-trimethoxybenzylidene)amino)-1 ,5 -dihydro-10H-spiro[acridine-9,2 -pyrrole]-4 -carbonitrile (AMTAC-17) was synthesized and tested for antitumor effects. Toxicity evaluation was performed in mice after acute treatment (2000 mg/kg, intraperitoneally, i.p.). The Ehrlich ascites carcinoma model was used to investigate the antitumor activity of AMTAC-17 (12.5, 25, or 50 mg/kg, i.p.) after seven days of treatment. Effects on the cell cycle, angiogenesis, and inflammatory responses were investigated. LD 50 (lethal dose 50%) was estimated to be higher than 5000 mg/kg. AMTAC-17 reduced the Ehrlich tumor's total viable cancer cells count and peritumoral micro-vessels density, and induced an increase in the sub-G1 peak. Additionally, there was an increase of Th1 cytokine profile levels (IL-1β, TNF-α, and IL-12). In conclusion, the spiro-acridine compound AMTAC-17 presents low toxicity, and its in vivo antitumor effect involves modulation of the immune system to a cytotoxic Th1 profile and a reduction of tumor angiogenesis.

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“…The volume of ascitic fluid was collected from the peritoneal cavity to determine the tumor volume (mL). Trypan blue assay was used to evaluate the cell viability [51].…”

Section: Evaluation Of In Vivo Antitumor Activity In the Ehrlich Ascimentioning

confidence: 99%

“…Concentrations of nitrite were calculated from a standard curve previously established with known molar concentrations of sodium nitrite. The tests were done in quadruplicate and the values expressed in µM [51].…”

Section: Quantification Of Nitrite Levels In the Ehrlich Ascites Carcmentioning

confidence: 99%

Toxicity and Antitumor Activity of a Thiophene–Acridine Hybrid

et al. 2019

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The antitumor effects of thiophene and acridine compounds have been described; however, the clinical usefulness of these compounds is limited due to the risk of high toxicity and drug resistance. The strategy of molecular hybridization presents the opportunity to develop new drugs which may display better target affinity and less serious side effects. Herein, 2-((6-Chloro-2-methoxy-acridin-9-yl)amino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]-thiophene-3-carbonitrile (ACS03), a hybrid thiophene–acridine compound with antileishmanial activity, was tested for toxicity and antitumor activity. The toxicity was evaluated in vitro (on HaCat and peripheral blood mononuclear cells) and in vivo (zebrafish embryos and acute toxicity in mice). Antitumor activity was also assessed in vitro in HCT-116 (human colon carcinoma cell line), K562 (chronic myeloid leukemic cell line), HL-60 (human promyelocytic leukemia cell line), HeLa (human cervical cancer cell line), and MCF-7 (breast cancer cell line) and in vivo (Ehrlich ascites carcinoma model). ACS03 exhibited selectivity toward HCT-116 cells (Half maximal inhibitory concentration, IC50 = 23.11 ± 1.03 µM). In zebrafish embryos, ACS03 induced an increase in lactate dehydrogenase, glutathione S-transferase, and acetylcholinesterase activities. The LD50 (lethal dose 50%) value in mice was estimated to be higher than 5000 mg/kg (intraperitoneally). In vivo, ACS03 (12.5 mg/kg) induced a significant reduction in tumor volume and cell viability. In vivo antitumor activity was associated with the nitric oxide cytotoxic effect. In conclusion, significant antitumor activity and weak toxicity were recorded for this hybrid compound, characterizing it as a potential anticancer compound.

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

Cited by 22 publications

References 60 publications

Piperine: A review of its biological effects

Piperine: A review of its biological effects

Antitumor Effect of a Novel Spiro-Acridine Compound is Associated with Up-Regulation of Th1-Type Responses and Antiangiogenic Action

Toxicity and Antitumor Activity of a Thiophene–Acridine Hybrid

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