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 sulphurinduced 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.
