RESUMO
Lung cancer is the leading cause of cancer deaths and the overall 5-year survival rate is less than 17%. Hyperthermia is an alternative approach for the treatment of lung cancer and is associated with fewer side effects. We employed ironoxide nanoparticles in inducing localized hyperthermia in lung cancer cells using a pulsed electromagnetic field (PEMF). We synthesized, characterized and determined the uptake of dipeptide-coated iron oxide nanoparticles. Further, their ability in inducing localized hyperthermia in PEMF on lung cancer cells was assessed. Results showed nanoparticles are non-cytotoxic and showed enhanced cellular uptake in lung cancer cells. In vivo studies in nude mice lung tumor xenografts confirmed the presence in the tumors. Lung cancer cells pretreated with dipeptide-coated magnetic nanoparticles upon PEMF exposure induced cell death.
Assuntos
Campos Eletromagnéticos , Neoplasias Pulmonares/genética , Nanopartículas de Magnetita/uso terapêutico , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos NusRESUMO
BACKGROUND: Triple-negative breast cancers represent an important clinical challenge, as these cancers do not respond to conventional endocrine therapies or other available targeted agents. Phycocyanin (PC), a natural, water soluble and non-toxic molecule is shown to have potent anti-cancer property. METHODS: In this study, we determined the efficacy of PC as an anti-neoplastic agent in vitro on a series of breast cancer cell lines. We studied effects of PC in inducing DNA damage and apoptosis through western blot and qPCR. Also, anti-metastatic and anti-angiogenic properties were studied by classic wound healing and vasculogenic mimicry assays. RESULTS: We found that triple negative MDA-MB-231 cells were most sensitive to PC (IC50 : 5.98 ± 0.95 µM) as compared to other cells. They also showed decreased cell proliferation and reduced colony formation ability upon treatment with PC. Profile of Cell cycle analysis showed that PC caused G1 arrest which could be attributed to decreased mRNA levels of Cyclin E and CDK-2 and increased p21 levels. Mechanistic studies revealed that PC induced apoptosis as evident by increase in percentage of annexin positive cells, increase in γ-H2AX levels, and by changing the Bcl-2/Bax ratio followed by release of cytochrome C and increased Caspase 9 levels. MDA MB 231 cells treated with PC resulted in decreased cell migration and increased cell adhesive property and also showed anti-angiogenic effects. We also observed that PC suppressed cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) production. All these biological effects of phycocyanin on MDA MB 231 cells could be attributed to decreased MAPK signaling pathway. We also observed that PC is non-toxic to non-malignant cells, platelets and RBC's. CONCLUSION: Taken together, these findings demonstrate, for the first time, that PC may be a promising anti-neoplastic agent for treatment of triple negative breast cancers.