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Plant Species from the Atlantic Forest Biome and Their Bioactive Constituents
Published in Luzia Valentina Modolo, Mary Ann Foglio, Brazilian Medicinal Plants, 2019
Rebeca Previate Medina, Carolina Rabal Biasetto, Lidiane Gaspareto Felippe, Lilian Cherubin Correia, Marília Valli, Afif Felix Monteiro, Alberto José Cavalheiro, Ângela Regina Araújo, Ian Castro-Gamboa, Maysa Furlan, Vanderlan da Silva Bolzani, Dulce Helena Siqueira Silva
Since 2011, several studies have focused on piperlongumine due to the compound's selective antitumor properties, comprising about 80 articles published worldwide, including some aimed to encourage and guide clinical trials. However, no studies addressing piperlongumine metabolism in human organism were known, until de Lima Moreira et al. (2016) investigated the compound's in vitro oxidation by Cytochrome P450 (CYP450) enzyme, in addition to the enzymatic kinetic profile catalyzed by CYP enzymes and the prediction of in vivo pharmacokinetic parameters. The structures of four piperlongumine metabolic products were also proposed by employing liquid chromatography coupled to high-resolution mass spectrometry (HR-LC-ESI-MS) analyses in both negative and positive ion modes and were confirmed on the basis of their fragmentation patterns in LC-IT-MS spectra. Subsequent isolation through LC-SPE-NMR (liquid chromatography-solid phase extraction-nuclear magnetic resonance) allowed 1H NMR assignments for the metabolites' characterization, which corroborated their structures. Phenotypic studies and possible piperlongumine-drug interactions were reported as well. Altogether, these results propitiate a useful guide to further clinical studies aimed at a rational exploration of piperlongumine potential in the development of antitumor drugs.
The Natural Alkaloid Piperlongumine Inhibits Metastatic Activity and Epithelial-to-Mesenchymal Transition of Triple-Negative Mammary Carcinoma Cells
Published in Nutrition and Cancer, 2021
Leanne M. Delaney, Nathan Farias, Javad Ghassemi Rad, Wasundara Fernando, Henry Annan, David W. Hoskin
The pungent fruits of the long pepper plant (Piper longum) are widely consumed as a spice, as well as being used in traditional medicine to treat a variety of ailments (8). Long pepper plant fruits contain piperlongumine, a bioactive alkaloid that selectively kills breast cancer cells and other cancer cell types (9–12). The cytotoxic activity of piperlongumine has been attributed to oxidative stress caused by increased levels of hydrogen peroxide in piperlongumine-treated cancer cells (13). Cancer cells typically have a greater reactive oxygen species (ROS) burden and are therefore more sensitive than normal cells to oxidative stress (14). Piperlongumine also inhibits the JAK2-STAT3 (15), nuclear factor (NF) κB (16), and phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling pathways (17), reduces overall nuclear traffic (18), and activates pro-apoptotic C/EBP homologous protein (9), mitogen-activated protein kinase p38 and phospho-c-Jun N-terminal kinase (11). However, the effect of noncytotoxic low dose piperlongumine on metastasis-associated molecules and activities of TNBC cells has not been fully investigated.
Piperlongumine Induces Apoptosis in Human Melanoma Cells Via Reactive Oxygen Species Mediated Mitochondria Disruption
Published in Nutrition and Cancer, 2018
Xuejiao Song, Tiantao Gao, Qian Lei, Lidan Zhang, Yuqin Yao, Jingyuan Xiong
Piperlongumine (Figure 1) is a natural alkaloid compound isolated from the long pepper (Piper longum) commonly grown in southeastern Asia and southern India. Piperlongumine and its derivatives are valuable natural products possessing anti-platelet aggregation, anti-inflammatory, and anti-tumor properties (12–15). The pharmacokinetic profiles and therapeutic potential of piperlongumine have been particularly documented, while no obvious adverse effects or toxicities were reported in humans (16). Thus, the functions of piperlongumine were intensively investigated under a variety of pathological conditions including arthritis, lupus nephritis, hyperlipidemic, autoimmune encephalomyelitis, and neurodegenerative diseases (17–20). Piperlongumine was reported to increase the level of reactive oxygen species (ROS) and apoptotic cell deaths in bladder, colon, breast, pancreatic, osteosarcoma, and lung cancer cells (15). Recent studies have demonstrated that piperlongumine exerts anticancer activity in breast, colon, ovarian, and prostate cell lines (21–24). In addition, piperlongumine was able to induce selective cell death in head-and-neck cancer cells through ROS rand c-Jun N-terminal kinases (JNKs) pathways (25). However, the precise anti-tumor effects of piperlongumine on malignant melanoma have not been fully elucidated.