Par-4-dependent p53 up-regulation plays a critical role in thymoquinone-induced cellular senescence in human malignant glioma cells

Karthikeyan Subburayan, Faisal Thayyullathil, Siraj Pallichankandy, Anees Rahman, Sehamuddin Galadari

Research output: Contribution to journalArticle

Abstract

Thymoquinone (TQ), the predominant bioactive constituent present in black cumin (Nigella sativa), exerts tumor suppressive activity against a wide variety of cancer cells. Cellular senescence, characterized by stable and long term loss of proliferative capacity, acts as a potent tumor suppressive mechanism. Here, we provide evidence for the first time that TQ suppresses growth of glioma cells by potentially inducing the expression of prostate apoptosis response-4 (Par-4) tumor suppressor protein. In turn, TQ-induced Par-4 expression triggers cellular senescence, as evidenced by increasing cellular size, β-galactosidase staining, G1 phase arrest, and increased expression of senescence markers such as p53, p21, Rb, and decreased expression of lamin B1, cyclin E and cyclin depended kinase-2 (CDK-2). Further, overexpression of Par-4 significantly increases the expression of p53 and its downstream target p21, and increases β-galactosidase positive cells, while siRNA/shRNA mediated-knockdown of Par-4 reverses the TQ-induced effects. Altogether, we describe a novel mechanism of cross talk between Par-4 and p53, that plays a critical role in TQ-induced senescence in human malignant glioma cells.

Original languageEnglish (US)
Pages (from-to)80-97
Number of pages18
JournalCancer Letters
Volume426
DOIs
StatePublished - Jul 10 2018

Fingerprint

Cell Aging
Glioma
Prostate
Up-Regulation
Apoptosis
Nigella sativa
Galactosidases
Small Interfering RNA
Tumor Suppressor Proteins
Cyclin E
Neoplasms
Cyclins
G1 Phase
Phosphotransferases
thymoquinone
Staining and Labeling
Growth

Keywords

  • p53
  • Par-4
  • Senescence
  • Thymoquinone
  • β-galactosidase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Par-4-dependent p53 up-regulation plays a critical role in thymoquinone-induced cellular senescence in human malignant glioma cells. / Subburayan, Karthikeyan; Thayyullathil, Faisal; Pallichankandy, Siraj; Rahman, Anees; Galadari, Sehamuddin.

In: Cancer Letters, Vol. 426, 10.07.2018, p. 80-97.

Research output: Contribution to journalArticle

Subburayan, Karthikeyan ; Thayyullathil, Faisal ; Pallichankandy, Siraj ; Rahman, Anees ; Galadari, Sehamuddin. / Par-4-dependent p53 up-regulation plays a critical role in thymoquinone-induced cellular senescence in human malignant glioma cells. In: Cancer Letters. 2018 ; Vol. 426. pp. 80-97.
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