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

Network pharmacology and molecular docking technology for exploring the effect and mechanism of Radix Bupleuri and Radix Paeoniae Alba herb-pair on anti-hepatitis: A review

“…Research has shown that piperine antimicrobial activity and cytotoxicity effects can be verified through molecular modeling. [ 33 , 34 ] Additionally, molecular modeling can also confirm the clinical therapeutic effects of different components such as geissoschizoline N4-methylchlorine and Eleutherine plicata by simulating molecular docking. [ 35 , 36 ] Consequently, in silico modeling offers the potential to develop new drug candidate ingredients with targeted effects.…”

Exploring the association between inflammatory biomarkers and gastric cancer development: A two-sample mendelian randomization analysis.

“…A comprehensive grasp of these mechanisms is vital for a holistic understanding of how inflammation influences gastric cancer pathogenesis. [ 42 – 44 ] The objective of the present study was to utilize a two-sample Mendelian randomization analysis, incorporating data from genome-wide association studies (GWAS), to probe the causal nexus between inflammatory biomarkers and the risk of gastric malignancy. By doing so, it seeks to uncover innovative avenues for the early prevention and management of GC, while also providing empirical guidance for the clinical treatment of gastric malignancy.…”

Molecular Aspects of Piperine in Signaling Pathways Associated with Inflammation in Head and Neck Cancer

“…The attention given to the study of this molecule is mainly due to its biological properties, such as: anti-inflammatory, antioxidant, immunomodulatory and anticancer, properties which allow this compound to chemically interact with various molecular targets. Specifically, in relation to piperine's anticancer activity, recent observations have shown that its mechanism of action is multiple and involves the activation of cell signaling pathways, such as cell proliferation, programmed cell death, decreased migration and invasion of cancer cells [7].…”