Cytochalasin B inhibits the proliferation of human glioma U251 cells through cell cycle arrest and apoptosis

Zg, Tong; Liu, Nan; Hs, Song; Li, J-Q; Jiang, Jiuyang; Jy, Zhu; Jp, Qi

doi:10.4238/2014.december.19.2

Cited by 9 publications

(5 citation statements)

References 38 publications

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“…Then, the absorbance at 490 nm was measured using an ELX800 Micro Plate Reader (Bio-Tec Instruments, Inc.). Excel FORECAST (predict x based on known x and y values) was used to predict the drug IC5025. Three independent experiments were performed in triplicate.…”

Section: Methodsmentioning

confidence: 99%

Attenuation of STAT3 Phosphorylation Promotes Apoptosis and Chemosensitivity in Human Osteosarcoma Induced by Raddeanin A

Wang

Zuo

et al. 2019

Int. J. Biol. Sci.

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Osteosarcoma (OS) is the most common primary bone malignancy in adolescents. One major obstacle for current OS treatment is drug-resistance. Raddeanin A (RA), an oleanane-type triterpenoid saponin, exerts anti-tumor effects in several tumor models, but the effect of RA in human drug-resistant OS remained to be elucidated. In the present study, we investigated the anti-tumor effects of RA in both drug-sensitive and drug-resistant OS cells and its underlying mechanism. RA inhibited cell proliferation and colony formation and induced apoptotic cell death in a dose-dependent manner in both drug-sensitive and drug-resistant cells. Moreover, RA exposure resulted in the inhibition of interleukin-6 (IL-6)-induced JAK2/STAT3 signaling pathway activation and target gene expression in both drug-sensitive and drug-resistant cells. Meanwhile, we observed significantly increased MDR1 and STAT3 expression in drug-resistant OS cells compared with parental cells. STAT3 overexpression promoted chemo-resistance and MDR1 protein expression in both drug-sensitive OS cells and drug-resistant OS cells, while inhibiting STAT3 with siRNA sensitized OS cells to doxorubicin treatment. In addition, RA synergistically increased doxorubicin toxicity by increasing its cellular uptake, ablating efflux and downregulating MDR1 in drug-resistant cells with attenuation of STAT3 Phosphorylation. Finally, RA suppressed in vivo tumor growth and induced apoptosis in nude mouse using drug-resistant OS tibia orthotopic model. Taken together, RA is a promising potential therapeutic for the treatment of doxorubicin resistance in OS.

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Section: Methodsmentioning

confidence: 99%

Attenuation of STAT3 Phosphorylation Promotes Apoptosis and Chemosensitivity in Human Osteosarcoma Induced by Raddeanin A

Wang

Zuo

et al. 2019

Int. J. Biol. Sci.

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“…After that, the absorbance was then measured using a model ELX800 Micro Plate Reader (Bio-Tec Instruments, Inc., Bio-Tek Winooski, VT, USA) at 490 nm. EXCEL FOR-CAST (x, known-y 0 s known-x 0 s) was used to predict the drug IC50 level [20]. Three independent experiments were carried out in triplicate.…”

Section: Cck8 Cell Viability Assaymentioning

confidence: 99%

Alternol, a natural compound, exerts an anti‐tumour effect on osteosarcoma by modulating of STAT3 and ROS/MAPK signalling pathways

Zuo

Zhou

Wang

et al. 2016

J Cellular Molecular Medi

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Osteosarcoma (OS) is the most frequent primary malignant bone tumour. Alternol, a novel compound purified from microbial fermentation products exerts anti‐tumour effects across several cancer types. The effect of alternol on human OS remains to be elucidated. We first evaluated the anti‐tumour effect of alternol in several human OS cell lines in vitro and investigated its underlying mechanism. Alternol inhibited OS cell proliferation, migration and induced caspase‐dependent apoptosis, G2/M cell cycle arrest in a dose and time‐dependent manner. Moreover, alternol treatment inhibited signal transducer and activator of transcription‐3 (STAT3) phosphorylation in 143B and MG63 human OS cells, as evaluated using a STAT3‐dependent dual luciferase reporter system. Exposure to alternol resulted in excessive reactive oxygen species (ROS) generation and Jun amino‐terminal kinases (JNK), extracellular signal‐regulated kinases (ERK1/2) and p38 activation. Furthermore, alternol‐induced cell death was significantly restored in the presence of the ROS scavenger, N‐acetyl‐l‐cysteine (NAC) or a caspase inhibitor Z‐VAD‐FMK. NAC also prevented G2/M phase arrest and phosphorylation of mitogen‐activated protein kinases (MAPK), but did not reverse STAT3 inactivation. Finally, alternol suppressed tumour growth in vivo in the nude mouse OS tibia orthotopic model. Immunohistochemistry revealed that alternol treatment resulted in down‐regulation of phosph‐STAT3 Tyr705 and up‐regulation of cleaved caspase‐3 and phosph‐SAPK (Stress‐activated protein kinases)/JNK expression. Taken together, our results reveal that alternol suppresses cell proliferation, migration and induces apoptosis, cell cycle arrest by modulating of ROS‐dependent MAPK and STAT3 signalling pathways in human OS cells. Therefore, alternol is a promising candidate for developing anti‐tumour drugs target OS.

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“…We propose that actin filaments function not only in the structure support, mobility, and contraction of cells but also as a signaling organizer and mediator to coordinate cellular signaling. By disrupting actin, cucurbitacin I, as well as other actin disruptors, altered JAK/STAT signaling and possibly caused cell cycle arrest and cell death [60,61] .…”

Section: Discussionmentioning

confidence: 99%

Cucurbitacin I inhibits STAT3, but enhances STAT1 signaling in human cancer cells in vitro through disrupting actin filaments

et al. 2017

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STAT1 and STAT3 are two important members of the STAT (signal transducers and activators of transcription) protein family and play opposing roles in regulating cancer cell growth. Suppressing STAT3 and/or enhancing STAT1 signaling are considered to be attractive anticancer strategies. Cucurbitacin I (CuI) isolated from the cucurbitacin family was reported to be an inhibitor of STAT3 signaling and a disruptor of actin cytoskeleton. In this study we investigated the function and mechanisms of CuI in regulating STAT signaling in human cancer cells in vitro. CuI (0.1-10 mmol/L) dose-dependently inhibited the phosphorylation of STAT3, and enhanced the phosphorylation of STAT1 in lung adenocarcinoma A549 cells possibly through disrupting actin filaments. We further demonstrated that actin filaments physically associated with JAK2 and STAT3 in A549 cells and regulated their phosphorylation through two signaling complexes, the IL-6 receptor complex and the focal adhesion complex. Actin filaments also interacted with STAT1 in A549 cells and regulated its dephosphorylation. Taken together, this study reveals the molecular mechanisms of CuI in the regulation of STAT signaling and in a possible inhibition of human cancer cell growth. More importantly, this study uncovers a novel role of actin and actin-associated signaling complexes in regulating STAT signaling.

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Cytochalasin B inhibits the proliferation of human glioma U251 cells through cell cycle arrest and apoptosis

Cited by 9 publications

References 38 publications

Attenuation of STAT3 Phosphorylation Promotes Apoptosis and Chemosensitivity in Human Osteosarcoma Induced by Raddeanin A

Attenuation of STAT3 Phosphorylation Promotes Apoptosis and Chemosensitivity in Human Osteosarcoma Induced by Raddeanin A

Alternol, a natural compound, exerts an anti‐tumour effect on osteosarcoma by modulating of STAT3 and ROS/MAPK signalling pathways

Cucurbitacin I inhibits STAT3, but enhances STAT1 signaling in human cancer cells in vitro through disrupting actin filaments

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