Sulphur alters NFκB-p300 cross-talk in favour of p53-p300 to induce apoptosis in non-small cell lung carcinoma

Saha,Shilpi; Bhattacharjee,Pushpak; Guha,Deblina; Kajal,Kirti; Khan,Poulami; Chakraborty,Sreeparna; Mukherjee,Shravanti; Paul,Shrutarshi; Manchanda,Rajkumar; Khurana,Anil; Nayak,Debadatta; Chakrabarty,Rathin; Sa,Gaurisankar; Das,Tanya

doi:10.3892/ijo.2015.3061

Sulphur alters NFκB-p300 cross-talk in favour of p53-p300 to induce apoptosis in non-small cell lung carcinoma

Authors:
- Shilpi Saha
- Pushpak Bhattacharjee
- Deblina Guha
- Kirti Kajal
- Poulami Khan
- Sreeparna Chakraborty
- Shravanti Mukherjee
- Shrutarshi Paul
- Rajkumar Manchanda
- Anil Khurana
- Debadatta Nayak
- Rathin Chakrabarty
- Gaurisankar Sa
- Tanya Das
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Affiliations: Division of Molecular Medicine, Bose Institute, P1/12, CIT Scheme VIIM, Kolkata-700054, India, Central Council for Research in Homeopathy, 61-65 Institutional Area, Janakpuri, New Delhi-110058, India, Bholanath Chakrabarty Trust, 5 Subol Koley Lane, Howrah 711101, India
Published online on: June 22, 2015 https://doi.org/10.3892/ijo.2015.3061
Pages: 573-582

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Abstract

Adverse side effects of chemotherapy during cancer treatment have shifted considerable focus towards therapies that are not only targeted but are also devoid of toxic side effects. We evaluated the antitumorigenic activity of sulphur, and delineated the molecular mechanisms underlying sulphur-induced apoptosis in non-small cell lung carcinoma (NSCLC) cells. A search for the underlying mechanism revealed that the choice between the two cellular processes, NFκBp65-mediated survival and p53-mediated apoptosis, was decided by the competition for a limited pool of transcriptional coactivator protein p300 in NSCLC cells. In contrast, sulphur inhibited otherwise upregulated survival signaling in NSCLC cells by perturbing the nuclear translocation of p65NFκB, its association with p300 histone acetylase, and subsequent transcription of Bcl-2. Under such anti-survival condition, induction of p53-p300 cross-talk enhanced the transcriptional activity of p53 and intrinsic mitochondrial death cascade. Overall, the findings of this preclinical study clearly delineated the molecular mechanism underlying the apoptogenic effect of the non-toxic homeopathic remedy, sulphur, in NSCLC cells.

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