cucurbitacin-d and Lung-Neoplasms

Lung cancer is one of the most common malignancies worldwide. To treat lung cancer, various anticancer drugs were developed and tested, but they failed because of drug resistance. In the present study, we tested herbal medicines, such as TK and CuD, as anticancer drugs to decrease side effects and resistance.. Cell viability was measured by an MTT assay. Analysis of cell cycle arrest was performed by flow cytometry. Induction of apoptosis by cucurbitacin D was measured by an annexin V-FITC/PI assay. We performed RTK kit analysis. Levels of p-ErbB3, p-STAT3, p-NF-κB, and caspases were measured by western blot analysis. Nuclear staining of ErbB3 was measured by immunocytochemistry. Transcriptional activity of STAT3 and NF-κB was detected by STAT3 and NF-κB luciferase reporter gene assays.. We found a synergistic effect of TK with CDDP and PXD in primary culture of human NSCLC tumor cells. The combination of CDDP/PXD and TK or CuD inhibited the proliferation of H1299 cells. The combination of CDDP/PXD and TK or CuD induced sub-G1 and G2/M cell cycle arrest in H1299 cells. The combination of CDDP/PXD and TK or CuD induced apoptosis, regulated apoptotic molecules, caused morphological changes and inhibited colony formation in H1299 cells. We found that TK suppresses p-ErbB3 expression and signaling. The combination of CDDP/PXD and TK or CuD inhibited p-AKT, p-Erk, and p-JNK signaling and suppressed Stat3 and NF-κB transcriptional activity in H1299 cells. More importantly, the combination of CDDP/PXD and TK or CuD inhibited p-ErbB3 and downstream molecules in H1299 cells. The combination of CDDP/PXD and TK or CuD inhibited ErbB2/ErbB3 dimerization. Our results clearly demonstrate that the synergistic effect of CDDP/PXD and TK or CuD inhibits cell growth and induces apoptosis by inhibiting ErbB3 signaling.. The combination of CDDP/PXD and TK or CuD decreases cell proliferation and induces apoptosis by inhibiting ErbB3 signaling in H1299 lung cancer cells. TK or CuD could be useful as a compound to treat lung cancer. Additionally, targeting ErbB3 may also be useful for treating lung cancer.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Caspases; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cisplatin; Drug Synergism; Drugs, Chinese Herbal; Humans; Lung Neoplasms; Pemetrexed; Receptor, ErbB-3; Signal Transduction; Trichosanthes; Triterpenes

Despite progress in chemotherapeutic agents, non-small cell lung cancers (NSCLC) still have a poor survival rate. Thus, development of new therapeutic strategies, specifically against cancer cells is still required. For this purpose, we treated the non-small cell lung cancer cell line NSCLC-N6 with the natural product cucurbitacin D (CucD) - extracted from the plant Ecballium elaterium in order first to assess its in vitro cytotoxicity, but also to study the genetic changes that it could bring out. CucD has shown a blocking in the G1 phase of the cell cycle in NSCLC-N6 cells prior to apoptotic cell death. The reverse transcriptase-polymerase chain reaction-differential display (RT-PCR-DD) technique was also applied on treated cells to elucidate the genetic mechanisms involved. We revealed an overexpression of Cyclin-dependent kinase 1 (CDK1) mRNA after treatment and, with the use of antisense oligonucleotides, an effective role in the proliferation arrest of NSCLC-N6 cells. The present study provides new insights about the mechanisms of proliferation arrest in tumor cells and open new ways of treatment to target tumor growth.

Topics: Antineoplastic Agents, Phytogenic; Carcinoma, Non-Small-Cell Lung; CDC2 Protein Kinase; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; RNA, Messenger; Triterpenes; Up-Regulation

A new cucurbitacin D analogue, 2-deoxycucurbitacin D (1), as well as cucurbitacin D (2) and 25-acetylcucurbitacin F (3) were isolated from Sloanea zuliaensis. Compound 1 was found only in the young leaves of the plant and not in the mature leaves, and its structure was established using spectroscopic means. Compounds 1-3 demonstrated potent cytotoxic activity against breast (MCF-7), lung (H-460), and central nervous system (SF-268) human cancer cell lines.

Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Central Nervous System Neoplasms; Drug Screening Assays, Antitumor; Elaeocarpaceae; Female; Humans; Lung Neoplasms; Molecular Structure; Panama; Plant Leaves; Plants, Medicinal; Triterpenes; Tumor Cells, Cultured