Anti-Proliferative Activities of Vasicinone on Lung Carcinoma Cells Mediated via Activation of Both Mitochondria-Dependent and Independent Pathways
Biomolecules & Therapeutics
; : 409-416, 2018.
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| ID: wpr-715613
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ABSTRACT
Vasicinone, a quinazoline alkaloid from Adhatoda vasica Nees. is well known for its bronchodilator activity. However its antiproliferative activities is yet to be elucidated. Here-in we investigated the anti-proliferative effect of vasicinone and its underlying mechanism against A549 lung carcinoma cells. The A549 cells upon treatment with various doses of vasicinone (10, 30, 50, 70 µM) for 72 h showed significant decrease in cell viability. Vasicinone treatment also showed DNA fragmentation, LDH leakage, and disruption of mitochondrial potential, and lower wound healing ability in A549 cells. The Annexin V/PI staining showed disrupted plasma membrane integrity and permeability of PI in treated cells. Moreover vasicinone treatment also lead to down regulation of Bcl-2, Fas death receptor and up regulation of PARP, BAD and cytochrome c, suggesting the anti-proliferative nature of vasicinone which mediated apoptosis through both Fas death receptors as well as Bcl-2 regulated signaling. Furthermore, our preliminary studies with vasicinone treatment also showed to lower the ROS levels in A549 cells and have potential free radical scavenging (DPPH, Hydroxyl) activity and ferric reducing power in cell free systems. Thus combining all, vasicinone may be used to develop a new therapeutic agent against oxidative stress induced lung cancer.
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WPRIM
Asunto principal:
Permeabilidad
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Justicia Social
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Cicatrización de Heridas
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Regulación hacia Abajo
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Regulación hacia Arriba
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Sistema Libre de Células
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Membrana Celular
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Supervivencia Celular
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Apoptosis
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Estrés Oxidativo
Idioma:
En
Revista:
Biomolecules & Therapeutics
Año:
2018
Tipo del documento:
Article