hyperoside and Lung-Neoplasms

Acquired epidermal growth factor receptor (EGFR) T790M mutation is the most common mechanism that accounts for EGFR‑TKI (tyrosine kinase inhibitor) resistance of non‑small cell lung cancer (NSCLC). High expense and acquired resistance weaken support for the use of osimertinib for T790M‑positive NSCLC treatment, and limit the efficacy and application of this drug. Hyperoside, a flavonol glycoside compound, extracted from Hypericum perforatum, has been reported to inhibit the growth of a variety of tumors. The present study aimed to investigate the role of hyperoside in treating NSCLC with T790M mutations, and to elucidate the underlying molecular mechanisms. Cell viability assays, apoptosis analysis, reverse transcription‑quantitative PCR, western blot analysis, animal experiments and immunohistochemistry were performed to examine the anticancer activity of hyperoside. Hyperoside inhibited the proliferation and induced the apoptosis of T790M‑positive NSCLC cells. Hyperoside upregulated forkhead box protein O1 (FoxO1) expression and downregulated the level of long non‑coding RNA (lncRNA) colon cancer associated transcript 1 (CCAT1) in T790M‑positive NSCLC cells. In the in vivo study, hyperoside inhibited the growth of T790M‑positive NSCLC xenografts. In conclusion, hyperoside inhibited proliferation and induced apoptosis by upregulating FoxO1 via CCAT1 in T790M‑positive NSCLC both in vitro and in vivo, suggesting that hyperoside is a novel candidate for T790M‑positive NSCLC treatment.

Topics: Animals; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Cell Survival; Forkhead Box Protein O1; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Male; Mice; Mutation; Quercetin; RNA, Long Noncoding; Up-Regulation; Xenograft Model Antitumor Assays

Lung cancer remains one of the most aggressive human malignancies with a low survival rate. Hyperoside (quercetin-3-O-β-d-galactopyranoside) is a flavonol glycoside with an anti-cancer activity. The microRNA-let-7 was widely regarded as a tumor suppressor in human tumors. Here, we investigated the role of hyperoside and let-7a-5p on the lung cancer cell proliferation, cell cycle and apoptosis in A549 cells in vitro. Our results showed that hyperoside could inhibit the proliferation of A549 cells through inducing apoptosis and G1/S phase arrest. Let-7a-5p could inhibit the proliferation of A549 cells via inhibiting the process of G1/S phase. Additionally, hyperoside and let-7a-5p had a synergetic effect on suppressing the proliferation of A549 cells; microRNA-let-7a-5p directly regulated the expression of CCND1 in A549 cells. Our study illustrated that hyperoside and microRNA-let7a-5p might provide a synergistic effect on anti-cancer, which may provide a new idea for lung cancer treatment.

Topics: 3' Untranslated Regions; A549 Cells; Cell Proliferation; Cell Survival; Cyclin D1; G1 Phase Cell Cycle Checkpoints; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; MicroRNAs; Quercetin

Hyperoside (quercetin-3-O-β-D-galactopyranoside) is a flavonol glycoside found in plants of the genera Hypericum and Crataegus, which exhibits anticancer, anti-oxidant, and anti-inflammatory activities. In this study we investigated whether autophagy was involved in the anticancer mechanisms of hyperoside in human non-small cell lung cancer cells in vitro.. Human non-small cell lung cancer cell line A549 was tested, and human bronchial epithelial cell line BEAS-2B was used for comparison. The expression of LC3-II, apoptotic and signaling proteins was measured using Western blotting. Autophagosomes were observed with MDC staining, LC3 immunocytochemistry, and GFP-LC3 fusion protein techniques. Cell viability was assessed using MTT assay.. Hyperoside (0.5, 1, 2 mmol/L) dose-dependently increased the expression of LC3-II and autophagosome numbers in A549 cells, but had no such effects in BEAS-2B cells. Moreover, hyperoside dose-dependently inhibited the phosphorylation of Akt, mTOR, p70S6K and 4E-BP1, but increased the phosphorylation of ERK1/2 in A549 cells. Insulin (200 nmol/L) markedly enhanced the phosphorylation of Akt and decreased LC3-II expression in A549 cells, which were reversed by pretreatment with hyperoside, whereas the MEK1/2 inhibitor U0126 (20 μmol/L) did not blocked hyperoside-induced LC3-II expression. Finally, hyperoside dose-dependently suppressed the cell viability and induced apoptosis in A549 cells, which were significantly attenuated by pretreatment with the autophagy inhibitor 3-methyladenine (2.5 mmol/L).. Hyperoside induces both autophagy and apoptosis in human non-small cell lung cancer cells in vitro. The autophagy is induced through inhibiting the Akt/mTOR/p70S6K signal pathways, which contributes to anticancer actions of hyperoside.

Topics: A549 Cells; Antineoplastic Agents; Apoptosis; Autophagy; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Quercetin; Signal Transduction

Though advanced surgical operation and chemotherapy have been under taken, lung cancer remains one of the most aggressive and fatal human malignancies with a low survival rate. Thus, novel therapeutic strategies for prevention and remedy are urgently needed in lung cancer. Hyperoside, known as quercetin-3-O-β-d-galactopyranoside, is a natural flavonol glycoside discovered in plants of genera Hypericum, displaying anti-oxidant, anticancer, and anti-inflammatory properties. In the study, we attempted to investigate whether hyperoside could inhibit lung cancer progression via Caspase-3- and P53-regulated cell death. In in vitro and in vivo experiments, we explored hyperoside at three different dosages on cell apoptosis, cell proliferation, cell migration, cell invasion, cell cycle distribution, the related signalling pathways, as well as xenograft tumor growth. Our data suggested that hyperoside exerted inhibitory role in lung cancer development. Inhibition of NF-κB transcriptional activity, Caspase-9/Caspase-3 activation, the cell cycle arrest, and suppression of cell proliferation-related signaling pathway led to the lung cancer inhibition. Further, via mice xenograft model in vivo, we indicated that hyperoside completely impeded tumor growth through angiogenesis inhibition. Our study illustrated that hyperoside might provide a synergistic anticancer effects that warrant further study and investigation due to its potential role in clinical applications.

Topics: A549 Cells; Animals; Antineoplastic Agents; Apoptosis; Caspase 3; Cell Cycle; Cell Movement; Cell Proliferation; Disease Progression; Humans; Lung Neoplasms; Male; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; NF-kappa B; Quercetin; Signal Transduction; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays

Lung cancer is one of the most common malignancies in the world and the most threatening cancer to human health. Effective therapies based on non-cytotoxic induction in cell inflammation- and apoptosis-responsive pathways are thought to represent a novel advance in treating lung cancer. However, many studies are still required for effective pharmaceutical to induce cancer cell death. Hyperoside (Hyp) is the chief component of some Chinese herbs with anticancer effect. Here, we investigated the role of hyperoside on the lung cancer cell migration, invasion, inflammation and apoptosis in A549 cells in vitro and xenografts of nude mice in vivo. A549 cells were injected in nude mice for establishing tumors. Our results showed that hyperoside suppressed the proliferation, migration and invasion. Additionally, apoptosis was induced by hyperoside via Bcl-2/Bax-regulated Caspase3 activation, suggesting that hyperoside might inhibit lung cancer progression through apoptotic induction. And also, hyperoside could prevent progression and development of lung cancer through inactivating NF-κB signaling pathway. Subsequently, inflammatory cytokines, including TNF-α, IL-6, IL-1β and IL-18, were down-regulated significantly. And animal experiments also illustrated that the tumor volume and weight were reduced after hyperoside administration, which was also through apoptosis induction and prevention of inflammation response by Caspase3 activation and NF-κB inactivation. To our knowledge, it was the first time to evaluate the effects of hyperoside on preventing progression and development of lung cancer in vivo and in vitro to assess the possible therapies of hyperoside as a future approach for preventing lung cancer progression and development.

Topics: A549 Cells; Apoptosis; Caspase 3; Cell Movement; Cell Shape; Cell Survival; Cytokines; Disease Progression; Humans; Inflammation; Lung Neoplasms; Neoplasm Invasiveness; NF-kappa B; Nitric Oxide; Quercetin; Signal Transduction