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

Abstract

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.

The Double Role of p53 in Cancer and Autoimmunity and Its Potential as Therapeutic Target

“…This strategy leads to the activation of p53, which in turns competes with NF-κB for the binding to p300. The favored p53–p300 complex antagonizes the anti-apoptotic activity of NF-κB-p300 complex by the activation of apoptosis-inducing Bax factor [66]. …”

Homeopathy: Curative, Concurrent and Supportive Cancer Treatment Potential

“…Sulphur is apoptotic to oral cancer, immortalized oral keratinocytes, and neuroblastoma cells [22]. Sulphur 6C, 30C, and 200C showed dose dependent apoptosis against the A549 non-small cell lung adenocarcinoma (NSCLC) cell line, with 20 μl/ml of Sulphur 30C being most cytotoxic, p<0.001 [22]. Sulphur disturbs p65NF-κβ nuclear translocation, association with p300 histone acetylase, and Bcl-2 transcription [22].…”

“…Sulphur 6C, 30C, and 200C showed dose dependent apoptosis against the A549 non-small cell lung adenocarcinoma (NSCLC) cell line, with 20 μl/ml of Sulphur 30C being most cytotoxic, p<0.001 [22]. Sulphur disturbs p65NF-κβ nuclear translocation, association with p300 histone acetylase, and Bcl-2 transcription [22]. Sulphur induces p53-p300 cross-talk, increasing p53 transcription and intrinsic mitochondrial death cascade [22].…”

“…Sulphur disturbs p65NF-κβ nuclear translocation, association with p300 histone acetylase, and Bcl-2 transcription [22]. Sulphur induces p53-p300 cross-talk, increasing p53 transcription and intrinsic mitochondrial death cascade [22].…”

Inflammatory cytokine IL6 cooperates with CUDR to aggravate hepatocyte-like stem cells malignant transformation through NF-κB signaling

“…In particular, m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation22. NF-κB is a key transcriptional regulator involved in inflammation and cell proliferation, survival, and transformation2324. For example, Metformin suppresses pancreatic tumor growth with inhibition of NFκB/STAT3 inflammatory signaling25.…”