Biomol Ther.  2018 Jul;26(4):409-416. 10.4062/biomolther.2017.097.

Anti-Proliferative Activities of Vasicinone on Lung Carcinoma Cells Mediated via Activation of Both Mitochondria-Dependent and Independent Pathways

Affiliations
  • 1Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam. kalitajk74@gmail.com
  • 2Centre for Biotechnology and Bioinformatics, Dibrugarh University, Dibrugarh 786004, Assam.
  • 3Academy of Scientific and Innovative Research, CSIR-North East Institute of Science and Technology Campus, Jorhat 785006, Assam.
  • 4Biological Sciences, Assam Downtown University, Guwahati 781026, India.

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.

Keyword

Vasicinone; Antioxidant; Anti-proliferative; A549 cells

MeSH Terms

Apoptosis
Cell Membrane
Cell Survival
Cell-Free System
Cytochromes c
DNA Fragmentation
Down-Regulation
Justicia
Lung Neoplasms
Lung*
Oxidative Stress
Permeability
Receptors, Death Domain
Up-Regulation
Wound Healing
Cytochromes c
Receptors, Death Domain
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