lignans and Adenocarcinoma-of-Lung

α-Conidendrin is a lignan isolated from Taxus wallichiana and other species. In the present study, we demonstrated that α-conidendrin inhibited the cell-surface expression of intercellular adhesion molecule-1 (ICAM-1) induced by tumor necrosis factor-α (TNF-α) at an IC

Topics: A549 Cells; Adenocarcinoma of Lung; Cell Survival; Chromans; Cyclooxygenase 2; E-Selectin; Human Umbilical Vein Endothelial Cells; Humans; Intercellular Adhesion Molecule-1; Lignans; Lung Neoplasms; Promoter Regions, Genetic; Signal Transduction; Tetrahydronaphthalenes; Transcription Factor RelA; Tumor Necrosis Factor-alpha

TMEM16A plays critical roles in physiological process and may serve as drug targets for diverse diseases. Recently, TMEM16A has started to be regarded as potential primary lung adenocarcinoma targets. Here, we identified that arctigenin, a natural compound, is a novel TMEM16A inhibitor, and it can suppress lung adenocarcinoma growth through inhibiting TMEM16A both in vitro and in vivo. Our data also showed that the IC

Topics: Adenocarcinoma of Lung; Animals; Anoctamin-1; Antineoplastic Agents; Cell Line; Furans; Humans; Lignans; Lung Neoplasms; MAP Kinase Signaling System; Mice, Inbred BALB C

Honokiol, a biphenolic neolignan with inappreciable toxicity isolated from Magnolia officinalis, has been reported to have antiangiogenic and antitumor properties in several tumor cell lines and tumor xenograft models. In our previous study, structural modification by chemical synthesis has been carried out to develop novel honokiol derivatives to improve antitumor activity and clarify the structure-activity relationship. Honokiol analogs, especially 3,5'-diformylated honokiol HK-(CHO)2, have been found to moderately block the newly grown segmental vessels from the dorsal aorta in the transgenic zebrafish-based assay, show antiangiogenic property, and exert medium cytotoxicity against two lung cell lines (Lewis lung carcinoma LL/2 cells and human non-small-cell lung cancer A549 cells). However, the in-vitro and in-vivo antitumor effects of formylated honokiol derivatives against lung carcinoma remained poorly understood. In the study, two formylated honokiol derivatives also showed potent antitumor effects in the Lewis lung carcinoma cells, K-ras-dirived lung adenocarcinoma mice, and a mouse lung tumor xenograft model, with HK-(CHO)2 being most efficacious. The potential mechanism was inhibiting cell proliferation and inducing apoptosis in lung cancer by the regulation of vascular endothelial growth factor A expression. These results further suggested that HK-(CHO)2 might be potential candidates for the treatment of lung carcinoma.

Topics: Adenocarcinoma of Lung; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Biphenyl Compounds; Carcinoma, Lewis Lung; Cell Proliferation; Female; Formates; Humans; Lignans; Lung Neoplasms; Mice; Mice, Inbred C57BL; Mice, Nude; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

The lignan arctigenin (ARG) from the herb Arctium lappa L. possesses anti-cancer activity, however the mechanism of action of ARG has been found to vary among tissues and types of cancer cells. The current study aims to gain insight into the ARG mediated mechanism of action involved in inhibiting proliferation and inducing apoptosis in lung adenocarcinoma cells. This study also delineates the cancer cell specificity of ARG by comparison with its effects on various normal cell lines. ARG selectively arrested the proliferation of cancer cells at the G0/G1 phase through the down-regulation of NPAT protein expression. This down-regulation occurred via the suppression of either cyclin E/CDK2 or cyclin H/CDK7, while apoptosis was induced through the modulation of the Akt-1-related signaling pathway. Furthermore, a GSH synthase inhibitor specifically enhanced the cytotoxicity of ARG against cancer cells, suggesting that the intracellular GSH content was another factor influencing the susceptibility of cancer cells to ARG. These findings suggest that specific cytotoxicity of ARG against lung cancer cells was explained by its selective modulation of the expression of NPAT, which is involved in histone biosynthesis. The cytotoxicity of ARG appeared to be dependent on the intracellular GSH level.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Antineoplastic Agents, Phytogenic; Apoptosis; Arctium; Cell Cycle Proteins; Cell Line; Cyclin E; Cyclin-Dependent Kinase 2; Cyclins; Down-Regulation; Furans; Glutathione; Humans; Lignans; Lung Neoplasms; Nuclear Proteins; Oncogene Proteins; Phytotherapy; Plant Extracts; Proto-Oncogene Proteins c-akt; Signal Transduction