Oncology Research Center, Federal University of Pará, Belém 66075-110, PA, Brazil.
Department of Physics, Federal University of Roraima, Boa Vista 69310-000, RR, Brazil.
Molecules. 2023 Jul 22;28(14):5587. doi: 10.3390/molecules28145587.
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 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 L. (Black pepper). Electronic (SEM) and optical microscopies, X-ray diffraction, nuclear magnetic resonance spectroscopies (C and H 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.
胃癌是全球最常见的肿瘤类型之一，通常表现为侵袭性和难以治疗的肿瘤。寻找具有抗癌潜力的新结构涵盖了一个广阔的研究领域，其中天然产物作为有前途的替代品出现。在这种情况下，胡椒碱作为 物种的一种生物碱，因其生物活性而受到关注，包括抗癌特性。本工作提出了三种从 L.（黑胡椒）中获得胡椒碱的不依赖加热、可靠、低成本和选择性方法。电子（SEM）和光学显微镜、X 射线衍射、核磁共振谱（C 和 H NMR）和光学光谱（UV-Vis、光致发光和 FTIR）证实了胡椒碱晶体的获得。MTT 测定表明，胡椒碱样品对来自巴西亚马逊的原发性和转移性胃癌细胞系模型表现出良好的细胞毒性。样品对评估模型表现出选择性细胞毒性，对具有更高侵袭性的细胞显示出更高的有效性。此外，研究的胡椒碱晶体表现出作为良好细胞毒性增强剂的能力，当与传统化疗药物（5-FU 和 GEM）联合使用时，允许药物在使用较低浓度的情况下在细胞中达到相同的细胞毒性效果。这些结果确立了胡椒碱作为治疗侵袭性胃癌的有前途的分子，无论是在其分离形式还是作为生物增强剂。
