Radiosensitizing potential of Plumbagin in B16F1 Melanoma Tumor Cells Through Mitochondrial Mediated Programmed Cell Death

Rao, Satish BS and Rayabandla, Sunil Kumar Mandala and Das, Shubhankar and Aithal, Kiran and Udupa, N (2015) Radiosensitizing potential of Plumbagin in B16F1 Melanoma Tumor Cells Through Mitochondrial Mediated Programmed Cell Death. Journal of Applied Biomedicine, 13. pp. 279-288.

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Abstract

The radiosensitizing potential of Plumbagin (PLB) against chemo- and radioresistant B16F1 melanoma cells growing in vitro was investigated. Clonogenic assay revealed a sensitization enhancement ratio (SER) of 1.5 for PLB treatment in combination with radiation. PLB pretreatment for 1 h prior to radiation resulted in elevated intracellular ROS levels compared to the group treated with radiation alone. Alkaline comet assay analysis revealed PLB's potential to enhance the radiation induced DNA damage. Cell cycle studies have shown enhanced G2/M arrest for combination treatment of PLB with radiation. Cell death exerted by PLB combination was mainly through programmed cell death, involving the depletion of mitochondrial membrane potential, increase in the expression of p53, Bax, Cytochrome c,PARP and Caspase 3 cleavage. In conclusion, this study demonstrates the radiosensitizing potential of PLB to inhibit the growth of melanoma cells in vitro, which may be attributed to the oxidative stress and DNA damage leading to enhanced mitochondria-mediated programmed cell death. Also, this study demonstrate the ability of PLB to augment ionizing radiation induced tumor cell kill which further warrant the avenue for the development of a clinically useful radiosensitizer.

Item Type: Article
Uncontrolled Keywords: Cell cycle arrest; DNA damage; Membrane potential; Radiosensitizer; Reactive oxygen species; Abbreviations: DCFH-DA; 20,70-dicholorofluorescein diacetate Cm, mitochondrial membrane; Potential PARP; Poly (ADP-ribose) polymerase PI; Propidium iodide PLB; Plumbagin RIPA; Radioimmunoprecipitation assay ROS; Reactive oxygen species RT; Radiation SER; Sensitization enhancement ratio SF; Surviving fraction
Subjects: Life Sciences > MLSC Manipal
Research > Research Center - Health Sciences
Depositing User: KMC Library
Date Deposited: 07 Dec 2015 09:39
Last Modified: 07 Dec 2015 09:39
URI: http://eprints.manipal.edu/id/eprint/144709

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