Thymoquinone inhibits microtubule polymerization by tubulin binding and causes mitotic arrest following apoptosis in A549 cells

Acharya, Bipul R.; Chatterjee, Arindam; Ganguli, Arnab; Bhattacharya, Surela; Chakrabarti, Gopal

doi:10.1016/j.biochi.2013.09.025

Cited by 38 publications

(21 citation statements)

References 39 publications

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“…Moreover, thymoquinone has been reported to possess antineoplastic activity against various cancers, including pancreatic (7), lung (8) and colon cancer (9) and leukemia (10). Studies have shown that thymoquinone inhibits the growth and induces cell apoptosis and cycle arrest, as well as represses metastasis and angiogenesis, which involves Akt (11), NF-κB signaling (12), mitogen-activated protein kinase (MAPK) (13) and STAT3 signaling pathways (14).…”

Section: Introductionmentioning

confidence: 99%

Thymoquinone inhibits epithelial-mesenchymal transition in prostate cancer cells by negatively regulating the TGF-β/Smad2/3 signaling pathway

et al. 2017

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Abstract. Thymoquinone, a major ingredient of black seed oil (Nigella sativa), has been shown to exhibit anticancer capacity in various types of cancers. However, there are few studies concerning the correlation between thymoquinone and epithelial-to-mesenchymal transition (EMT) in prostate cancer. In the present study, we firstly found that thymoquinone showed antimetastatic capacity in prostate cancer DU145 and PC3 cells. Additionally, thymoquinone reversed EMT by increasing E-cadherin expression and decreasing vimentin and Slug expression in a concentration-dependent manner. Recent studies have shown that the transforming growth factor-β (TGF-β) signaling pathway may be associated with EMT. Intriguingly, the expression of TGF-β, Smad2 and Smad3 at the mRNA and protein levels was notably reduced upon thymoquinone treatment in prostate cancer DU145 and PC3 cells. Subsequently, we confirmed that thymoquinone repressed metastasis and EMT of prostate cancer through downregulation of the TGF-β/Smad2/3 signaling pathway, which may be partially reversed by TGF-β overexpression. In summary, our findings demonstrated that thymoquinone suppressed the metastatic phenotype and reversed EMT of prostate cancer cells by negatively regulating the TGF-β/Smad2/3 signaling pathway. These findings suggest that thymoquinone is a potential therapeutic agent against prostate cancer which functions by targeting TGF-β.

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Section: Introductionmentioning

confidence: 99%

Thymoquinone inhibits epithelial-mesenchymal transition in prostate cancer cells by negatively regulating the TGF-β/Smad2/3 signaling pathway

et al. 2017

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“…In recent years, numerous reports have indicated that colchicine exhibits potent antitumor activity against various tumor cell lines, such as liver, colon, gastric and lung cancer cells (14)(15)(16)(17)(18)(19). In the present study, the inhibitory effect of colchicine on HT-29 colon cancer cells was investigated and the possible molecular mechanism involved was elucidated.…”

Section: Discussionmentioning

confidence: 82%

Colchicine induces apoptosis in HT-29 human colon cancer cells via the AKT and c-Jun N-terminal kinase signaling pathways

Huang

Peng

2015

Molecular Medicine Reports

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Colchicine is a natural compound, which belongs to the botanical family Colchicaceae and prevents growth of cancer cells via antimitotic activity by interacting with microtubules. Although numerous studies have demonstrated that the effect of colchicine on cell apoptosis is mediated by the activation of caspase‑3, the signaling pathways involved in the process remain unknown. In the current study, evidence is presented regarding the missing information using HT‑29 human colon cancer cells. The effect of colchicine on apoptosis in HT‑29 cells and the apoptosis‑associated signaling pathways were determined using various methods, including cell viability assay, Annexin V/propidium idodide (PI) binding, PI staining, Hoechst 33342 staining, mitochondrial membrane potential (Δψm) assay, reactive oxygen species (ROS) assay and western blot analysis. Colchicine was observed to induce a dose‑dependent reduction in cell viability in HT‑29 cells and early apoptosis occurred when the cells were treated with 1 µg/ml colchicine. Furthermore, colchicine treatment induced a loss of Δψm, increased ROS production, activated caspase‑3, upregulated BAX expression and downregulated Bcl‑2 expression, which evidenced the colchicine activity on apoptosis, potentially by acting via the intrinsic apoptotic signaling pathway. Colchicine increased phosphorylation of p38, although not phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase, which indicates that colchicine activates the p38 signaling pathway in order to induce cell apoptosis. Therefore, colchicine exhibited significant growth inhibition of the HT‑29 colon cancer cell line and induced apoptosis in the cells via the mitochondrial pathway, which is regulated by p38 signaling pathways.

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“…Fig 1A shows a schematic representation of the chemical structure of KPU-300, a novel anti-microtubule agent that possesses a unique 2-pyridyl structure [ 16 ]. When cells were treated with 30 nM KPU-300, microtubule structures were disrupted and the mitotic spindle was not formed ( Fig 1B ), both characteristic consequences of treatment with inhibitors of microtubule polymerization [ 36 – 38 ]. We next examined the kinetics of Fucci fluorescence in HeLa-Fucci cells following treatment with various concentrations of KPU-300 ( Fig 1C , upper panel).…”

Section: Resultsmentioning

confidence: 99%

KPU-300, a Novel Benzophenone–Diketopiperazine–Type Anti-Microtubule Agent with a 2-Pyridyl Structure, Is a Potent Radiosensitizer That Synchronizes the Cell Cycle in Early M Phase

et al. 2015

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KPU-300 is a novel colchicine-type anti-microtubule agent derived from plinabulin (NPI-2358). We characterized the effects of KPU-300 on cell cycle kinetics and radiosensitization using HeLa cells expressing the fluorescent ubiquitination-based cell cycle indicator (Fucci). Cells treated with 30 nM KPU-300 for 24 h were efficiently synchronized in M phase and contained clearly detectable abnormal Fucci fluorescence. Two-dimensional flow-cytometric analysis revealed a fraction of cells distinct from the normal Fucci fluorescence pattern. Most of these cells were positive for an M phase marker, the phosphorylated form of histone H3. Cells growing in spheroids responded similarly to the drug, and the inner quiescent fraction also responded after recruitment to the growth fraction. When such drug-treated cells were irradiated in monolayer, a remarkable radiosensitization was observed. To determine whether this radiosensitization was truly due to the synchronization in M phase, we compared the radiosensitivity of cells synchronized by KPU-300 treatment and cells in early M phase isolated by a combined method that took advantage of shake-off and the properties of the Fucci system. Following normalization against the surviving fraction of cells treated with KPU-300 alone, the surviving fractions of cells irradiated in early M phase coincided. Taken together with potential vascular disrupting function in vivo, we propose a novel radiosensitizing strategy using KPU-300.

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Thymoquinone inhibits microtubule polymerization by tubulin binding and causes mitotic arrest following apoptosis in A549 cells

Cited by 38 publications

References 39 publications

Thymoquinone inhibits epithelial-mesenchymal transition in prostate cancer cells by negatively regulating the TGF-β/Smad2/3 signaling pathway

Thymoquinone inhibits epithelial-mesenchymal transition in prostate cancer cells by negatively regulating the TGF-β/Smad2/3 signaling pathway

Colchicine induces apoptosis in HT-29 human colon cancer cells via the AKT and c-Jun N-terminal kinase signaling pathways

KPU-300, a Novel Benzophenone–Diketopiperazine–Type Anti-Microtubule Agent with a 2-Pyridyl Structure, Is a Potent Radiosensitizer That Synchronizes the Cell Cycle in Early M Phase

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