Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent. (June 2020)

• Record Type: Journal Article
• Authors: Tripathi, Surya Kant; Biswal, Bijesh Kumar
• Is Part Of: Pharmacological research. Volume 156(2020)
• Publication Date: 2020-06
• Subjects: ROS reactive oxygen species -- PI3K phosphatidylino sitol-3-kinase -- AKT protein kinase B -- Gsk3β glycogen synthase kinase 3 beta -- mTOR mammalian target of rapamycin -- RAS rat sarcoma -- RAF v-raf murine sarcoma viral oncogene homolog B1 -- MEK mitogen- activated protein kinase -- ERK extracellular signal-regulated kinase -- Keap1 Kelch-like ECH-associated protein 1 -- Nrf- 2 nuclear factor erythroid 2 (NFE2)-related factor 2 -- TNFα tumor necrosis factor alpha -- IKKβ small molecule inhibitors of IκB kinase β -- IκBα nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells -- CDK cyclin-dependent kinase -- STAT3 signal transducer and activator of transcription 3 -- HK2 hexokinases2 -- SETDB1 SET domain bifurcated histone lysine methyltransferase 1 -- FosB FBJ murine osteosarcoma viral oncogene homolog B -- PARP poly ADP ribose polymerase -- JNK c-Jun N-terminal kinase -- Cyto C cytochrome C -- Bcl-2 B-cell lymphoma 2 -- Bax Bcl-2 associated X -- HO1 heme oxygenase -- CIAP-1/2 cellular inhibitor of apoptosis protein-1/2 -- VEGF vascular endothelial growth factor -- TWIST twist-related protein 1 -- MMP-9 matrix metallopeptidase 9 -- CXCR-4 C-X-C chemokine receptor type 4 -- IL-6 interleukin 6 -- ABCG1 ATP binding cassette subfamily G member 1 -- P-gp1 permeability glycoprotein 1 -- MRP1 multidrug resistance-associated protein 1 -- GSH glutathione; Piperlongumine -- Cancer -- Cytotoxicity -- Drug resistance -- Combination therapy -- Pharmaceutical relevance; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.104772
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Piperlongumine, a white to beige biologically active alkaloid/amide phytochemical, has high pharmacological relevance as an anticancer agent. Piperlongumine has several biological activities, including selective cytotoxicity against multiple cancer cells of different origins at a preclinical level. Several preclinical studies have documented the anticancer potential of piperlongumine through its targeting of multiple molecular mechanisms, such as cell cycle arrest, anti-angiogenesis, anti- invasive and anti-metastasis pathways, autophagy pathways, and intrinsic apoptotic pathways in vitro and in vivo . Mechanistically, piperlongumine inhibits cancer growth by resulting in the accumulation of intracellular reactive oxygen species, decreasing glutathione and chromosomal damage, or modulating key regulatory proteins, including PI3K, AKT, mTOR, NF-kβ, STATs, and cyclin D1. Furthermore, combined treatment with piperlongumine potentiates the anticancer activity of conventional chemotherapeutics and overcomes resistance to chemo- and radio- therapy. Nanoformulation of piperlongumine has been associated with increased aqueous solubility and bioavailability and lower toxicity, thus enhancing therapeutic efficacy in both preclinical and clinical settings. The current review highlights anticancer studies on the occurrence, chemical properties, chemopreventive mechanisms, toxicity, bioavailability, and pharmaceutical relevance of piperlongumine in vitro and in vivo.