piplartine and Carcinoma--Non-Small-Cell-Lung

Non-small cell lung cancer is a common type of lung cancer. Piperlongumine (PL), which is extracted from the roots of piperaceae plant, long pepper, and peppercorn, is an alkaloid amide that inhibits tumor growth and metastasis. However, whether it affects lung cancer cells remains unclear.. We assessed the effects of PL on the proliferation and apoptosis of A549 and H1299 NSCLC cell lines.. PL was mildly toxic to normal human bronchial epithelial cells and significantly suppressed growth and facilitated apoptosis of A549 and H1299 cells. It also upregulated microRNA (miR)-34b-3p and downregulated the transforming growth factor beta type I receptor (TGFBR1). The dual-luciferase reporter assay showed that TGFBR1 is a target gene of miR-34b-3p. Silencing of miR-34b-3p or overexpression of TGFBR1 partially attenuated the effects of PL on A549 and H1299 cells.. PL inhibits proliferation and induces apoptosis of A549 and H1299 cells by upregulating miR-34b-3p and modulating TGFBR1 signaling pathway.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Cell Proliferation; Dioxolanes; Female; Gene Expression Regulation, Neoplastic; Humans; Mice; Mice, Inbred BALB C; MicroRNAs; Receptor, Transforming Growth Factor-beta Type I; Signal Transduction; Up-Regulation; Xenograft Model Antitumor Assays

Cancers are one of the leading causes of deaths nowadays. The development of new treatment schemes for oncological diseases is an interesting direction in experimental medicine. Therefore, the evaluation of the influence of two alkaloids-piperlongumine (PL), sanguinarine (SAN) and their combination-on the basic life processes of the A549 cell line was considered reasonable.. The aim was achieved by analyzing the cytotoxic effects of PL and SAN and their combination in the ratio of 4:1 on the induction of cell death, changes in the distribution of cell cycle phases, reorganization of cytoskeleton and metastatic potential of A549 cells. The versatility of the applied concentration ratio was evaluated in terms of other cancer cell lines: MCF-7, H1299 and HepG2.. The results obtained from the MTT assay indicated that the interaction between the alkaloids depends on the concentration and type of cells. Additionally, the compounds and their combination did not exhibit a cytotoxic effect against normal cells. The combined effects of PL and SAN increased apoptosis and favored metastasis inhibition.. Selected alkaloids exhibit a cytotoxic effect on A549 cells. In turn, treatment with the combination of PL and SAN in a 4:1 ratio indicates a synergistic effect and is associated with an increase in the level of reactive oxygen species (ROS).

Topics: Anti-Infective Agents; Apoptosis; Benzophenanthridines; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Cell Movement; Cell Proliferation; Dioxolanes; Drug Synergism; Humans; Isoquinolines; Lung Neoplasms; Neoplasm Invasiveness; Reactive Oxygen Species; Tumor Cells, Cultured

Natural products with potent activity and less toxicity provide major sources for development of novel anti-cancer drugs. Herein, we evaluated the effects and the underlying mechanisms of a novel piperlongumine (PL) analogue L50377 on non-small-cell lung cancer (NSCLC) cells. The results revealed that L50377 displayed greater potentials of suppressing cell growth than PL. In addition, L50377 promoted cell apoptosis and pyroptosis via stimulating reactive oxygen species (ROS) generation in NSCLC cells. More interestingly, ROS mediated NF-κB suppression might be implicated in the mechanisms of L50377-induced pyroptosis in NSCLC cells. Taken together, our results suggested that L50377 served as a novel chemical agent might have great potentials for NSCLC treatment.

Topics: Antineoplastic Agents, Phytogenic; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Dioxolanes; Humans; Lung Neoplasms; NF-kappa B; Pyroptosis; Reactive Oxygen Species

Deregulation of glycolysis is a common phenomenon in human non-small cell lung cancer (NSCLC). In the present study, we reported the natural compound, piperlongumine, has a profound anti-tumor effect on NSCLC via regulation of glycolysis. Piperlongumine suppressed the proliferation, colony formation and HK2-mediated glycolysis in NSCLC cells. We demonstrated that exposure to piperlongumine disrupted the interaction between HK2 and VDAC1, induced the activation of the intrinsic apoptosis signaling pathway. Moreover, our results revealed that piperlongumine down-regulated the Akt signaling, exogenous overexpression of constitutively activated Akt1 in HCC827 and H1975 cells significantly rescued piperlongumine-induced glycolysis suppression and apoptosis. The xenograft mouse model data demonstrated the pivotal role of suppression of Akt activation and HK2-mediated glycolysis in mediating the

Topics: Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Dioxolanes; Flow Cytometry; Gene Expression Regulation, Neoplastic; Glycolysis; Humans; Immunoblotting; Immunohistochemistry; Immunoprecipitation; Lung Neoplasms; Signal Transduction

Piperlongumine has anti-cancer activity in numerous cancer cell lines via various signaling pathways. But there has been no study regarding the mechanisms of PL on the lung cancer yet. Thus, we evaluated the anti-cancer effects and possible mechanisms of PL on non-small cell lung cancer (NSCLC) cells in vivo and in vitro. Our findings showed that PL induced apoptotic cell death and suppressed the DNA binding activity of NF-κB in a concentration dependent manner (0-15 μM) in NSCLC cells. Docking model and pull down assay showed that PL directly binds to the DNA binding site of nuclear factor-κB (NF-κB) p50 subunit, and surface plasmon resonance (SPR) analysis showed that PL binds to p50 concentration-dependently. Moreover, co-treatment of PL with NF-κB inhibitor phenylarsine oxide (0.1 μM) or p50 siRNA (100 nM) augmented PL-induced inhibitory effect on cell growth and activation of Fas and DR4. Notably, co-treatment of PL with p50 mutant plasmid (C62S) partially abolished PL-induced cell growth inhibition and decreased the enhanced expression of Fas and DR4. In xenograft mice model, PL (2.5-5 mg/kg) suppressed tumor growth of NSCLC dose-dependently. Therefore, these results indicated that PL could inhibit lung cancer cell growth via inhibition of NF-κB signaling pathway in vitro and in vivo.

Topics: A549 Cells; Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dioxolanes; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Models, Molecular; Molecular Docking Simulation; NF-kappa B; Protein Binding; Signal Transduction; Xenograft Model Antitumor Assays