Benzamide riboside induced mitochondrial mediated apoptosis in human lung cancer H520 cells

MicroRNAs (miRNAs) are short ~21-nt non-coding RNA molecules that have been shown to regulate a number of biological processes. Previous reports have shown that overexpression of miR-128 in glioma cells inhibited cell proliferation. Literature also suggests that miR-128 negatively regulates prostate cancer cell invasion. Here, we show that overexpression of hsa-miR-128, a brain-enriched microRNA, induces apoptosis in HEK293T cells as elucidated by apoptosis assay, cell cycle changes, loss of mitochondrial membrane potential and multicaspase assay. By in silico analysis, we identified a putative target site within the 3' untranslated region (UTR) of Bax, a proapoptotic member of the apoptosis pathway. We found that ectopic expression of hsa-miR-128 suppressed a luciferase reporter containing the Bax-3' UTR and reduced the levels of Bax in HEK293T cells. Taken together, our study demonstrates that overexpression of hsa-miR-128 not only induces apoptosis in HEK293T cells but also is an endogenous regulator of Bax protein.

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“…These values were then normalized to b-actin. All experiments were repeated at least three times; representative results are presented [16].…”

Section: Western Blottingmentioning

confidence: 99%

MicroRNA-128 downregulates Bax and induces apoptosis in human embryonic kidney cells

Adlakha

Saini

2010

Cell. Mol. Life Sci.

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“…These signals include two pathways: a mitochondria-mediated pathway and a ligand-mediated death pathway (22). Upon triggering of either pathway, caspases, which are the final executioners of apoptosis, are activated and cause degradation of cellular proteins and disassembly of cells (23). Caspase-3 is responsible for the proteolytic cleavage of many key proteins, such as the nuclear enzyme poly polymerase (24).…”

Section: Discussionmentioning

confidence: 99%

Recombinant H2 relaxin inhibits apoptosis and induces cell proliferation in cultured leiomyoma cells without affecting those in cultured normal myometrial cells

Suzuki

Nakabayashi

Yamada

et al. 2012

Fertility and Sterility

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“…IMPDH inhibitor mycophenolate mofetil induces cell-cycle arrest and decreases T- and B-cell responses effectively, both in vitro and in vivo 7. IMPDH inhibitors tiazofurin, selenazofurin and benzamide riboside were previously tested for their antitumor properties8 and were found to induce differentiation and/or apoptosis in various cell systems, including leukemia HL-609,10 and K-562,11 melanoma12 and human lung cancer H520 13. Floryk et al .…”

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confidence: 99%

Antiproliferative effects of AVN944, a novel inosine 5‐monophosphate dehydrogenase inhibitor, in prostate cancer cells

Floryk

Thompson

2008

Intl Journal of Cancer

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Inosine 5-monophosphate dehydrogenase II, a key enzyme in the de novo synthesis of purine nucleotides, is expressed in prostate tumors and prostate cancer cells. AVN944 is a new, specific, noncompetitive IMPDH inhibitor. In this study, we investigated the effects of IMPDH inhibitor AVN944 on LNCaP, CWR22Rv1, DU145 and PC-3 human prostate cancer cells. AVN944 inhibited proliferation of these 4 prostate cancer cell lines and was associated with cell cycle G1 arrest of LNCaP cells and S-phase block of androgen-independent CWR22Rv1, DU145 and PC-3 cells. AVN944 induced caspase-dependent and caspase-independent cell death in LNCaP, CWR22Rv1, and DU145 cells. AVN944 induced expression of p53-target proteins Bok, Bax and Noxa in androgenresponsive cell lines and suppressed expression of survivin in prostate cancer cells regardless of their androgen sensitivity. AVN944 also induced differentiation of androgen-independent prostate cancer cells as indicated by morphological changes and increased expression of genes coding for prostasomal proteins, keratins and other proteins, including tumor suppressor genes MIG-6 and NDRG1. AVN944-differentiated androgen-independent DU145 and PC-3 cells are sensitized to TRAIL-induced apoptosis as demonstrated by induction of caspases and PARP cleavage. In summary, AVN944 inhibited the growth of human prostate cancer cells by inducing cell cycle arrest, cell death as well as differentiation. AVN944 is a novel, promising therapeutic agent that might be combined with other agents for treatment of human prostate cancer. ' 2008 Wiley-Liss, Inc.Key words: AVN944; IMPDH; prostate cancer; cell death; differentiation; TRAIL Prostate cancer is the most commonly diagnosed malignancy in men and is second only to lung cancer as the cause of cancer death in males. In 2008, it has been estimated that 186,320 men in the United States will be diagnosed with prostate cancer, and that 28,660 will die from the disease.1 Unfortunately, there is no cure for locally advanced or metastatic prostate cancer. Therefore, it is imperative that new strategies for the effective management and/ or treatment of this disease be found.Several lines of research have identified inosine 5-monophosphate dehydrogenase (IMPDH) as an attractive target for pharmacological intervention. IMPDH is a key enzyme in the de novo synthesis of purine nucleotides. Two isoforms of IMPDH were identified in humans, type I and type II.2 Each of the genes encodes a protein of 514 amino acids, with high homology between the isoforms (84% amino acid identity).Jackson et al. 3 and Weber 4 linked IMPDH with proliferation and malignancy and observed that the enzyme is upregulated in rapidly proliferating tumor cells. Elevated activity of IMPDH is primarily caused by upregulation of IMPDH II. Allison et al. 5 demonstrated that lymphocytes in particular are dependent on the de novo pathways of nucleotide biosynthesis, making IMPDH a target for immunosuppressive therapy. IMPDH I was also recently identified as an antiangiogenic drug target by Ch...

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Benzamide riboside induced mitochondrial mediated apoptosis in human lung cancer H520 cells

Cited by 24 publications

References 25 publications

MicroRNA-128 downregulates Bax and induces apoptosis in human embryonic kidney cells

MicroRNA-128 downregulates Bax and induces apoptosis in human embryonic kidney cells

Recombinant H2 relaxin inhibits apoptosis and induces cell proliferation in cultured leiomyoma cells without affecting those in cultured normal myometrial cells

Antiproliferative effects of AVN944, a novel inosine 5‐monophosphate dehydrogenase inhibitor, in prostate cancer cells

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