title: Sulphur alters NFκB-p300 cross-talk in favour of p53-p300 to induce apoptosis in non-small cell lung carcinoma.
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.
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, CIT Scheme VIIM, Kolkata-700054, India.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Saha
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, CIT Scheme VIIM, Kolkata-700054, India.
authors.forename: Pushpak
authors.initials: P
authors.lastname: Bhattacharjee
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, CIT Scheme VIIM, Kolkata-700054, India.
authors.forename: Deblina
authors.initials: D
authors.lastname: Guha
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, CIT Scheme VIIM, Kolkata-700054, India.
authors.forename: Kirti
authors.initials: K
authors.lastname: Kajal
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, CIT Scheme VIIM, Kolkata-700054, India.
authors.forename: Poulami
authors.initials: P
authors.lastname: Khan
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, CIT Scheme VIIM, Kolkata-700054, India.
authors.forename: Sreeparna
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, CIT Scheme VIIM, Kolkata-700054, India.
authors.forename: Shravanti
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, CIT Scheme VIIM, Kolkata-700054, India.
authors.forename: Shrutarshi
authors.initials: S
authors.lastname: Paul
authors.affiliation: Central Council for Research in Homeopathy, 61-65 Institutional Area, Janakpuri, New Delhi-110058, India.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Manchanda
authors.affiliation: Central Council for Research in Homeopathy, 61-65 Institutional Area, Janakpuri, New Delhi-110058, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Khurana
authors.affiliation: Central Council for Research in Homeopathy, 61-65 Institutional Area, Janakpuri, New Delhi-110058, India.
authors.forename: Debadatta
authors.initials: D
authors.lastname: Nayak
authors.affiliation: Bholanath Chakrabarty Trust, 5 Subol Koley Lane, Howrah 711101, India.
authors.forename: Rathin
authors.initials: R
authors.lastname: Chakrabarty
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, CIT Scheme VIIM, Kolkata-700054, India.
authors.forename: Gaurisankar
authors.initials: G
authors.lastname: Sa
authors.affiliation: Division of Molecular Medicine, Bose Institute, P1/12, CIT Scheme VIIM, Kolkata-700054, India.
authors.forename: Tanya
authors.initials: T
authors.lastname: Das
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013455:Sulfur / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D013455:Sulfur; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human