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SRJ23, a potent inducer of cell cycle arrest and apoptosis in prostate cancer cells
Author(s) -
Wong Hui Chyn,
Sagineedu Sreenivasa Rao,
Loke Seng Cheong,
Lajis Nordin Haji,
Stanslas Johnson
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.851.9
Subject(s) - apoptosis , lncap , annexin , dna fragmentation , cell cycle , chemistry , flow cytometry , cyclin dependent kinase 1 , cyclin b1 , microbiology and biotechnology , programmed cell death , cell cycle checkpoint , cancer cell , cancer research , biology , biochemistry , cancer , genetics
SRJ23 exhibited selectivity against prostate cancer cells in the USA NCI in vitro anticancer screen (Jada et al., 2008. Br J Pharmacol 155: 641–654). MTT assay was used in assessing in vitro growth inhibition of compounds against PC‐3, DU‐145 and LNCaP cells. Flow cytometry was used to analyse cell cycle distribution whereas fluorescence microscopy was performed to determine morphological cell death. DNA fragmentation and annexin V‐FITC/PI flow cytometry were performed to confirm apoptosis induced by SRJ23. Quantitation of cell cycle and apoptotic proteins were determined by immunoblotting. SRJ23 exerted selectivity towards PC‐3 cells. Mechanistically, SRJ23‐treated PC‐3 cells down‐regulated CDK1 without affecting levels of CDK4 and cyclin D1 to induce G2/M arrest which led to apoptosis. Apoptosis was further confirmed by DNA fragmentation and annexin V‐FITC which displayed inhibition in the presence of caspase 8 inhibitor (Z‐IETD‐FMK). Apoptosis was associated with increase in caspase 8 expression and activation. This thought to have induced cleavage of Bid into t‐Bid. Additionally, expression and activation of caspase 9 and Bax proteins were apparent, with concomitant down‐regulation of Bcl‐2 protein. Taken together, these support the potential of SRJ23 as a new anti‐prostate cancer agent. This research project is supported by Universiti Putra Malaysia via RUGS grant scheme.