Kinetin riboside preferentially induces apoptosis by modulating Bcl-2 family proteins and caspase-3 in cancer cells

Choi, Bo-Hwa; Kim, Wanil; Wang, Chelsia Qiuxia; Kim, Dong-Chan; Tan, Swee Ngin; Yong, Jean Wan Hong; Kim, Kyong‐Tai; Yoon, Ho Sup

doi:10.1016/j.canlet.2007.11.014

Cited by 67 publications

(48 citation statements)

References 27 publications

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“…Apoptosis is an important method of maintaining the balance between cell division and cell death, 33 and the induction of apoptosis in tumor cells is an important focus of antitumor drug discovery. 34 This study demonstrates that morphological changes occur in the nucleus of SO-Rb 50 cells following treatment with CNPs for 24 hours. Flow analysis revealed a dose-dependent increase in apoptosis in CNP-treated SO-Rb 50 cells.…”

Section: Discussionmentioning

confidence: 60%

Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model

Li¹,

Wu²,

Li³

et al. 2012

IJN

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Background: Celastrol, a Chinese herbal medicine, has shown antitumor activity against various tumor cell lines. However, the effect of celastrol on retinoblastoma has not yet been analyzed. Additionally, the poor water solubility of celastrol restricts further therapeutic applications. The goal of this study was to evaluate the effect of celastrol nanoparticles (CNPs) on r etinoblastoma and to investigate the potential mechanisms involved. Methods: Celastrol-loaded poly(ethylene glycol)-block-poly(ε-caprolactone) nanopolymeric micelles were developed to improve the hydrophilicity of celastrol. The 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulf-ophenyl)-2H tetrazolium monosodium salt (WST-8) assay was used to determine the inhibitory effect of CNPs on SO-Rb 50 cell proliferation in vitro. Immunofluorescence was used to evaluate the apoptotic effect of CNPs on nuclear morphology, and flow cytometry was used to quantify cellular apoptosis. The expression of Bcl-2, Bax, NF-κB p65, and phospo-NF-κB p65 proteins was assessed by Western blotting. A human retinoblastoma xenograft model was used to evaluate the inhibitory effects of CNPs on retinoblastoma in NOD-SCID mice. Hematoxylin and eosin staining was used to assess the apoptotic effects of CNPs on retinoblastoma. Results: CNPs inhibit the proliferation of SO-Rb 50 cells in a dose-and time-dependent manner with an IC 50 of 17.733 µg/mL (celastrol-loading content: 7.36%) after exposure to CNPs for 48 hours. CNPs induce apoptosis in SO-Rb 50 cells in a dose-dependent manner. The expression of Bcl-2, NF-κB p65, and phospo-NF-κB p65 proteins decreased after exposure to CNPs 54.4 µg/mL for 48 hours. Additionally, the Bax/Bcl-2 ratio increased, whereas the expression of Bax itself was not significantly altered. CNPs inhibit the growth of retinoblastoma and induce apoptosis in retinoblastoma cells in mice. Conclusion: CNPs inhibit the growth of retinoblastoma in mouse xenograft model by inducing apoptosis in SO-Rb 50 cells, which may be related to the increased Bax/Bcl-2 ratio and the inhibition of NF-κB. CNPs may represent a potential alternative treatment for retinoblastoma.

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Section: Discussionmentioning

confidence: 60%

Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model

Li¹,

Wu²,

Li³

et al. 2012

IJN

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“…Cell viability was assessed by measuring the activity of metabolizing 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide (Choi et al, 2008). A total of 1.0 Â 10 4 cells were seeded onto a 96-well plate and cultured up to a confluency of 90%.…”

Section: Cell Viability Assaymentioning

confidence: 99%

Obtusilactone B from Machilus Thunbergii Targets Barrier-to-Autointegration Factor to Treat Cancer

et al. 2012

Self Cite

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Targeting specific molecules is a promising cancer treatment because certain types of cancer cells are dependent on specific oncogenes. This strategy led to the development of therapeutics that use monoclonal antibodies or small-molecule inhibitors. However, the continued development of novel molecular targeting inhibitors is required to target the various oncogenes associated with the diverse types and stages of cancer. Obtusilactone B is a butanolide derivative purified from Machilus thunbergii. In this study, we show that obtusilactone B functions as a small-molecule inhibitor that causes abnormal nuclear envelope dynamics and inhibits growth by suppressing vaccinia-related kinase 1 (VRK1)-mediated phosphorylation of barrier-to-autointegration factor (BAF). BAF is important in maintaining lamin integrity, which is closely associated with diseases that include cancer. Specific binding of obtusilactone B to BAF suppressed VRK1-mediated BAF phosphorylation and the subsequent dissociation of the nuclear envelope from DNA that allows cells to progress through the cell cycle. Obtusilactone B potently induced tumor cell death in vitro, indicating that specific targeting of BAF to block cell cycle progression can be an effective anticancer strategy. Our results demonstrate that targeting a major constituent of the nuclear envelope may be a novel and promising alternative approach to cancer treatment.

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“…Caspase-3 activation is considered the central and final apoptotic marker enzyme for both mitochondrial intrinsic and death-domain receptor-dependent extrinsic pathways. Poly(ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair, is a substrate for caspase-3 (19). Therefore, we investigated the protein levels and activity of caspase-3.…”

Section: Effects Of 7-pec On Caspase-3 Activitymentioning

confidence: 99%

Induction of apoptosis by 7-piperazinethylchrysin in HCT-116 human colon cancer cells

et al. 2012

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Abstract. The antitumor activity of 7-piperazinethylchrysin (7-PEC) was investigated in HCT-116 human colon cancer cells. MTT assay revealed that the IC 50 of 7-PEC in HCT-116 cells was 1.5 µM after 72 h of treatment, much lower than that of chrysin (>100 µM). The data showed that 7-PEC was able to inhibit the growth of HCT-116 cells in a concentration-and time-dependent manner. Topical morphological changes of apoptotic body formation after 7-PEC treatment were observed by Hoechst 33258 staining. 7-PEC reduced mitochondrial membrane potential (∆Ψm) of cells in a concentration-dependent manner and increased the production of intracellular reactive oxygen species (ROS). After treatment with 7-PEC, a significant increase of Bax protein expression and decrease of Bcl-2 protein expression were observed at the same time. These events paralleled with activation of p53, caspase-3 and -9 and the release of cytochrome c (cyt-c), as well as poly(ADPribose) polymerase-1 (PARP1) cleavage and downregulation of p-Akt. However, the apoptosis induced by 7-PEC was blocked by Ac-DEVD-CHO, a caspase-3 inhibitor. These results demonstrate that 7-PEC-induced mitochondrial dysfunction in HCT-116 human colon cancer cells triggers events responsible for caspase-dependent apoptosis pathways, and the elevated ratio of Bax/Bcl-2 is likely involved in this effect.

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Kinetin riboside preferentially induces apoptosis by modulating Bcl-2 family proteins and caspase-3 in cancer cells

Cited by 67 publications

References 27 publications

Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model

Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model

Obtusilactone B from Machilus Thunbergii Targets Barrier-to-Autointegration Factor to Treat Cancer

Induction of apoptosis by 7-piperazinethylchrysin in HCT-116 human colon cancer cells

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