Abstract Title:

Dimethoxycurcumin, a metabolically stable analogue of curcumin enhances the radiosensitivity of cancer cells: Possible involvement of ROS and thioredoxin reductase.

Abstract Source:

Biochem Biophys Res Commun. 2016 Jul 2. Epub 2016 Jul 2. PMID: 27381867

Abstract Author(s):

Sundarraj Jayakumar, R S Patwardhan, Debojyoti Pal, Deepak Sharma, Santosh K Sandur

Article Affiliation:

Sundarraj Jayakumar

Abstract:

Dimethoxycurcumin (DIMC), a structural analogue of curcumin has been shown to have more stability, bioavailability, and effectiveness than its parent molecule curcumin. In this paper the radiosensitizing effect of DIMC has been investigated in A549 lung cancer cells. As compared to its parent molecule curcumin, DIMC showed a very potent radiosensitizing effect as seen by clonogenic survival assay. DIMC in combination with radiation significantly increased the apoptosis and mitotic death. This combinatorial treatment also leads to effective elimination of cancer stem cells. Further, there was a significant increase in cellular ROS, thereby decrease in GSH to GSSG ratio and also significant slowdown in DNA repair when DIMC was combined with radiation. In silico docking studies and in vitro studies showed inhibition of thioredoxin reductase enzyme by DIMC. Overexpression of thioredoxin leads to the abrogation of radiosensitizing effect of DIMC underscoring the role of thioredoxin reductase in radiosensitization. Our results clearly demonstrate that DIMC can synergistically enhance the cancer cell killing when combined with radiation by targeting thioredoxin system.

Study Type : In Vitro Study

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Sayer Ji
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