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Extraction, Characterization, and Evaluation of the Cytotoxic Activity of Piperine in Its Isolated form and in Combination with Chemotherapeutics against Gastric Cancer

Authors

Keywords:

piperine, extraction and purification, green extraction, cytotoxicity, gastric cancer

Abstract

Gastric cancer is one of the most frequent types of neoplasms worldwide, usually presenting as aggressive and difficult-to-manage tumors. The search for new structures with anticancer potential encompasses a vast research field in which natural products arise as promising alternatives. In this scenario, piperine, an alkaloid of the Piper species, has received attention due to its biological activity, including anticancer attributes. The present work proposes three heating-independent, reliable, low-cost, and selective methods for obtaining piperine from Piper nigrum L. (Black pepper). Electronic (SEM) and optical microscopies, X-ray diffraction, nuclear magnetic resonance spectroscopies (13C and 1H NMR), and optical spectroscopies (UV–Vis, photoluminescence, and FTIR) confirm the obtention of piperine crystals. The MTT assay reveals that the piperine samples exhibit good cytotoxic activity against primary and metastasis models of gastric cancer cell lines from the Brazilian Amazon. The samples showed selective cytotoxicity on the evaluated models, revealing higher effectiveness in cells bearing a higher degree of aggressiveness. Moreover, the investigated piperine crystals demonstrated the ability to act as a good cytotoxicity enhancer when combined with traditional chemotherapeutics (5-FU and GEM), allowing the drugs to achieve the same cytotoxic effect in cells employing lower concentrations. These results establish piperine as a promising molecule for therapy investigations in aggressive gastric cancer, both in its isolated form or as a bioenhancer. Keywords: piperine, extraction and purification, green extraction, cytotoxicity, gastric cancer

Author Biographies

Ingryd Ramos, Oncology Research Center, Federal University of Pará, Belém 66075-110, PA, Brazil; [email protected] (M.F.d.S.); [email protected] (P.P.d.A.); [email protected] (A.S.K.)

Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data curation, Writing – original draft, Writing – review & editing, Visualization

Davi Brasil, Institute of Technology, Federal University of Pará, Belém 66075-110, PA, Brazil; [email protected] (J.N.C.); [email protected] (D.d.S.B.B.)

Investigation, Resources, Supervision, Funding acquisition

Paulo Assumpção, Oncology Research Center, Federal University of Pará, Belém 66075-110, PA, Brazil; [email protected] (M.F.d.S.); [email protected] (P.P.d.A.); [email protected] (A.S.K.)

Investigation, Resources, Funding acquisition

Marcondes Costa, Institute of Geosciences, Federal University of Pará, Belém 66075-110, PA, Brazil; [email protected]

Methodology, Investigation, Resources

Fabrine Alves, Graduate Program in Pharmaceutical Innovation, Federal University of Pará, Belém 66075-110, PA, Brazil; [email protected]

Methodology, Investigation, Writing – original draft

Jefferson Lopes, Department of Physics, Federal University of Roraima, Boa Vista 69310-000, RR, Brazil; [email protected]

Methodology, Formal analysis, Investigation, Data curation, Writing – original draft, Writing – review & editing

André Khayat, Oncology Research Center, Federal University of Pará, Belém 66075-110, PA, Brazil; [email protected] (M.F.d.S.); [email protected] (P.P.d.A.); [email protected] (A.S.K.)

Validation, Formal analysis, Investigation, Resources, Writing – review & editing, Supervision, Project administration, Funding acquisition

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