Novel role of thiadiazolidine derivatives in inducing cell death through Myc-Max, Akt, FKHR, and FasL pathway

Pongali B. Raghavendra, Niteen Pathak, Sunil K. Manna

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    The 1,2,4-thiadiazolidine derivatives show anti-fungal and anti-inflammatory activities. We previously reported that these derivatives inhibit nuclear factor-kappaB (NF-κB), a transcription factor that induces tumorigenesis through activation of several genes. We have aimed to elucidate the mechanism of apoptosis mediated by these derivatives. In this study we provide evidence that dichlorophenyl form of thiadiazolidine (designated as P3-25) is a potential inducer of cell death by arresting cell cycle at G1 phase and decreases the amounts of cyclin D1 and cyclin E without interfering p16 and p27. It decreased c-Myc level and thereby inhibited DNA binding ability of Myc-Max complex. P3-25 dephosphorylated Rb and Akt facilitating nuclear translocation of FKHR that then expressed gene FasL. Activated FasL inhibited cell proliferation and induced cell death. Our results suggest that P3-25 derivative exerts anti-tumor activities by decreasing Myc-mediated response and increasing FasL expression, which may help in designing drugs for tumor therapy.

    Original languageEnglish
    Pages (from-to)495-503
    Number of pages9
    JournalBiochemical Pharmacology
    Volume78
    Issue number5
    DOIs
    Publication statusPublished - 01-09-2009

    Fingerprint

    Cell death
    Cell Death
    Derivatives
    Cyclin E
    Cyclin D1
    G1 Phase
    Helper-Inducer T-Lymphocytes
    Transcriptional Activation
    Tumors
    Neoplasms
    Cell Cycle
    Carcinogenesis
    Anti-Inflammatory Agents
    Transcription Factors
    Genes
    Cell Proliferation
    Apoptosis
    Drug Therapy
    DNA
    Cell proliferation

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Pharmacology

    Cite this

    Raghavendra, Pongali B. ; Pathak, Niteen ; Manna, Sunil K. / Novel role of thiadiazolidine derivatives in inducing cell death through Myc-Max, Akt, FKHR, and FasL pathway. In: Biochemical Pharmacology. 2009 ; Vol. 78, No. 5. pp. 495-503.
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    Novel role of thiadiazolidine derivatives in inducing cell death through Myc-Max, Akt, FKHR, and FasL pathway. / Raghavendra, Pongali B.; Pathak, Niteen; Manna, Sunil K.

    In: Biochemical Pharmacology, Vol. 78, No. 5, 01.09.2009, p. 495-503.

    Research output: Contribution to journalArticle

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