Biological and physical approaches on the role of piplartine (piperlongumine) in cancer

Abstract

Chronic inflammation provides a favorable microenvironment for tumorigenesis, which opens opportunities for targeting cancer development and progression. Piplartine (PL) is a biologically active alkaloid from long peppers that exhibits anti-inflammatory and antitumor activity. In the present study, we investigated the physical and chemical interactions of PL with anti-inflammatory compounds and their effects on cell proliferation and migration and on the gene expression of inflammatory mediators. Molecular docking data and physicochemical analysis suggested that PL shows potential interactions with a peptide of annexin A1 (ANXA1), an endogenous anti-inflammatory mediator with therapeutic potential in cancer. Treatment of neoplastic cells with PL alone or with annexin A1 mimic peptide reduced cell proliferation and viability and modulated the expression of MCP-1 chemokine, IL-8 cytokine and genes involved in inflammatory processes. The results also suggested an inhibitory effect of PL on tubulin expression. In addition, PL apparently had no influence on cell migration and invasion at the concentration tested. Considering the role of inflammation in the context of promoting tumor initiation, the present study shows the potential of piplartine as a therapeutic immunomodulator for cancer prevention and progression.

Nobiletin and Xanthohumol Sensitize Colorectal Cancer Stem Cells to Standard Chemotherapy

“…Compounds 6, Before assessing the effects of the Nobiletin-containing fraction (NCF), the Xanthohumolcontaining fraction (XCF), and their combination (Mix) on tumor cells, we studied their impact on the viability of two healthy cell lines. The human stromal cells, HS-5, and the human umbilical vein endothelial cells, HUVEC, have been extensively described as reliable models to estimate and predict the side effects of anti-cancer drugs on healthy cells [44][45][46]. The two cell lines were treated with increasing concentrations of the two fractions for 24 and 48 h and only mild effects on cell viability were observed, supporting the absence of significant toxicity of Nobiletin and Xanthohumol (Figure S1A,B).…”

Annexin A1 Mimetic Peptide and Piperlongumine: Anti-Inflammatory Profiles in Endotoxin-Induced Uveitis

“…Our investigations indicated that PL attenuated systemic and pulmonary inflammatory changes, partially by modulating the expression of the endogenous AnxA1, in lung inflammation induced by cigarette smoke [42]. The potential of PL as a therapeutic immunomodulator for cancer prevention and progression was reinforced by analyzing PL administration in human cancer cells from an epidermoid carcinoma of the larynx (Hep-2) and umbilical vein endothelial cells (HUVEC), in which PL modulated the expression of genes involved in inflammatory processes [36]. Although there are several publications related to PL, few studies have focused on its anti-inflammatory role, and the actions of PL in ocular inflammation are not known.…”

“…In recent years, another potent anti-inflammatory mediator, piperlongumine (PL) (5,6-dihydro-1-[(2E)-1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)pyridinone), a biologically active component of Piper species (Piperaceae), has attracted the attention of our research group for its possible interaction with AnxA1 [36]. In particular, PL is the main alkaloid of long pepper (Piper longum L.), and its pharmacological actions include cytotoxic, antitumor, antiangiogenic, antiplatelet, antibacterial, antidiabetic, antianxiolytic, antiatherosclerotic, and antifungal effects [36][37][38][39][40][41][42][43]. PL induces apoptosis by interfering with redox and reactive oxygen species (ROS) homeostatic regulators, such as glutathione S-transferase pi 1 (GSTP1) and carbonyl reductase (CBR1) [44].…”

“…Ac2-26 and PL interaction has been explored by our group through different molecular or computational screening techniques, such as phage display and molecular docking [36]. In silico analyses showed that, among other PL molecules, there was a terpene that appeared to interact with lysine 9 from AnxA1 in the region corresponding to the N-terminal peptide Ac2-26 [36].…”

“…Ac2-26 and PL interaction has been explored by our group through different molecular or computational screening techniques, such as phage display and molecular docking [36]. In silico analyses showed that, among other PL molecules, there was a terpene that appeared to interact with lysine 9 from AnxA1 in the region corresponding to the N-terminal peptide Ac2-26 [36]. However, the physiological reason for this interaction, whether positive or negative in vivo, with regard to the anti-inflammatory effects of AnxA1 is not yet understood, which opens up a new and stimulating field for research.…”