vicenin-ii and Lung-Neoplasms

Non-small cell lung cancer (NSCLC) has a very high rate of incidence and is resistant to chemo- and radiotherapy. Vicenin-2 (VCN-2) is a flavonoid obtained from Ocimum sanctum L. and it has been reported to have radioprotective, anticancer, and radiosensitizing properties. We have conducted this study to check the effect of VCN-2 on the cell viability and the effect on PTEN (Phosphatase and tensin homolog), PI3KCA (Phosphatidylinositol 4, 5-biphosphate 3-kinase catalytic subunit alpha isoform/PI3K 110α subunit), and Akt1 when VCN-2 was used alone and in combination with radiation in the NSCLC cell line NCI-H23 (H23). We have also checked the effect of VCN-2 on various pro- and anti-apoptotic genes and the ultra-morphological changes that occurred in the cells when VCN-2 is used alone and in combination with radiation. VCN-2 was able to lower cancer cell survival and phosphorylated Akt while promoting the expression of pro-apoptotic genes and down-regulating anti-apoptotic genes. We also observed the apoptosis-associated ultra-morphological changes in the VCN-2-treated cells. Our study have demonstrated that VCN-2 can be a potential chemotherapeutic and radiosensitizing agent in NSCLC. © 2018 BioFactors, 45(2):200-210, 2019.

Topics: Apigenin; Apoptosis; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Survival; Chromones; Glucosides; Humans; Lung Neoplasms; Morpholines; Nuclear Proteins; Ocimum sanctum; Protein Carbonylation; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Radiation-Sensitizing Agents; Reactive Oxygen Species; Transcription Factors

Topics: Antineoplastic Agents; Apigenin; Benzamides; Cell Line, Tumor; Cell Movement; Cell Survival; Chromones; Dendrobium; Dioxoles; Drug Screening Assays, Antitumor; Drug Therapy, Combination; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Glucosides; Humans; Lung Neoplasms; Molecular Structure; Morpholines; Phosphatidylinositol 3-Kinases; Plant Extracts; Plant Leaves; Proto-Oncogene Proteins c-akt; Signal Transduction; Structure-Activity Relationship; TOR Serine-Threonine Kinases; Transforming Growth Factor beta1

Non-small cell lung cancer (NSCLC) is a major form of cancer and is resistant to chemo- and radio-therapy. Vicenin-2 (VCN-2) is a flavonoid obtained from Ocimum sanctum L. and it has been reported to have radioprotective and anti-cancer properties. This study was conducted to check for the radiosensitizing potential of VCN-2 in the NSCLC cell line, NCI-H23. NCI-H23 cells were exposed to VCN-2 singularly, and to X-rays with and without prior VCN-2 treatment. Cytotoxicity assay, cell proliferation assay, caspase-3 activity assay, DNA fragmentation assay and Western blotting for Rad50, MMP-2 and p21 were performed to investigate the radiosensitizing properties of VCN-2. Fibroblast survival assay was performed using HEK293T cells to check for any adverse effects of VCN-2 on normal fibroblast cell line. VCN-2 singularly and in combination with radiation reduced the surviving cancer cells, increased caspase-3 activity, increased DNA fragmentation, increased the levels of Rad50 and lowered levels of MMP-2 and p21 proteins while being non-toxic and radioprotective to the fibroblast cells. VCN-2 showed a potent radiosensitizing property while also showing a chemotherapeutic property against NSCLC cell line NCI-H23.

Topics: Acid Anhydride Hydrolases; Apigenin; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclin-Dependent Kinase Inhibitor p21; DNA Repair Enzymes; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Glucosides; HEK293 Cells; Humans; Lung Neoplasms; Matrix Metalloproteinase 2; Radiation-Sensitizing Agents