MPT0B169 and MPT0B002, New Tubulin Inhibitors, Induce Growth Inhibition, G2/M Cell Cycle Arrest, and Apoptosis in Human Colorectal Cancer Cells

Lee, Chih Hsin; Lin, Yuan; Chen, Yen Chou; Wong, Shuit Mun; Juan, Shu Hui; Huang, Huei Mei

doi:10.1159/000492494

Cited by 6 publications

(4 citation statements)

References 19 publications

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“…Interfering with α-tubulin or β-tubulin expression causes G2-M cell cycle arrest due to disrupted microtubule dynamics [19][20] . The same results were obtained after disruption of tubulin polymerization by the addition of speci c chemical agents to the animal cell culture medium, which was accompanied by apoptosis [21][22] . Overexpression of tubulin-associated RITA decreased the levels of cyclin D1, cyclin E, CDK2, HES-1, and NF-kappaB p65, resulting in growth inhibition and inducing G0-G1 phase arrest in SMMC7721 and HepG2 cells [23] .…”

Section: Discussionsupporting

confidence: 66%

Tubulin beta 4B chain is involved in the cell cycle process of mouse spermatogonia through CDK2

Mao

Zeng

Kuang

et al. 2022

Preprint

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Tubb4b (tubulin beta-4b chain) is essential for spermatogonia cell growth and development as a microtubule network protein, and its regulatory mechanism remains to be studied. To deeply understand the role of Tubb4b in spermatogonia cell proliferation and the cell cycle, we studied the role of spermatogonia in the control and TUBB4B-KO groups in different cell cycle phases by flow cytometry. We detected the crucial protein CDK2 in each stage by qRT–PCR and Western blotting. The results showed that under the induction of serum starvation, thymidine, and nocodazole under different conditions, mouse spermatogonia remained in the G0-G1 phase, S phase, and G2-M phase, respectively, and the change in the spermatogonia cycle in the Tubb4b-KO group was slower than that in the control group. In the study of cycle synchronization, it was found that the mRNA level of Cdk2 in the G2-M phase increased significantly (P < 0.001), accompanied by the accumulation of CDK2 protein. In the Tubb4b-KO group, the mRNA level of Cdk2 increased significantly in the G0-G1 phase (P < 0.05), decreased significantly in the S phase (P < 0.05) and was accompanied by the fluctuation of CDK2 protein. These data suggest that Tubb4b has the potential to play an important role during the spermatogonial cell cycle by affecting the fluctuating expression of CDK2.

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Section: Discussionsupporting

confidence: 66%

Tubulin beta 4B chain is involved in the cell cycle process of mouse spermatogonia through CDK2

Mao

Zeng

Kuang

et al. 2022

Preprint

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“…The biological functions of normal cells experience major changes during carcinogenesis to promote the progression of cancer, including invasion and metastasis (31,32). Various tissue cells in an organism maintain a quantitative balance through proliferation and apoptosis, however, disturbing this balance leads to diseases such as cancer (33,34). Apoptosis is the main mechanism of cell death induced by various anticancer drugs, thus, the role of apoptosis in cancer therapy has become a focus in antitumor research (35,36).…”

Section: Discussionmentioning

confidence: 99%

miR-217 inhibits the migration and invasion of HeLa cells through modulating MAPK1

Zhu

Yang

Wang³

2019

Int J Mol Med

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MicroRNA (miR)-217 serves a pivotal role in the progression of colorectal cancer, renal cell carcinoma and glioma, however, the role of miR-217 in cervical cancer (CC) remains unclear. In the present study, the mechanism of miR-217 in cervical cancer was explored. The mRNA expression of miR-217 and mitogen-activated protein kinase 1 (MAPK1) were assessed using reverse transcription-quantitative polymerase chain reaction analysis. Cell Counting-Kit 8, wound-healing and Transwell assays were performed to detect cell viability, migration and invasion, respectively. Apoptosis and cell cycle were determined by flow cytometry. TargetScan 7.2 and dual-luciferase reporter assays were respectively used to determine miR-217 target genes and their binding capacities. The protein expression levels of MAPK1, phosphorylated (p)-extracellular signal-regulated kinase 1/2 (ERK1/2)/ERK1/2, Bcl-2, Bax and cleaved caspase-3 were quantified by western blotting. It was found that miR-217 was downregulated in patients with CC and in CC cells. The viability, migration and invasion of cells were suppressed by a miR-217 mimic. It was also found that apoptosis was increased and cell cycle was inhibited by the miR-217mimic, which was supported by changes in Bcl-2, Bax and cleaved caspase-3. MAPK1 was upregulated in patients with CC and was a target gene of miR-217. MAPK1 reversed the inhibition of miR-217 on cell viability, migration, invasion and apoptosis. The protein levels of MAPK1 and p-ERK1/2, which were higher in the mimic MAPK1 group than those in the control or mimic groups, were ameliorated by PD98059. The results of the present study demonstrated that miR-217 had an anti-CC effect and may be effectively used in the treatment of CC.

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“…The results obtained clearly showed that PTC‐028 induced the accumulation of cells at the G2/M phase (Figure 4A). The disruption of tubulin assembly was previously shown to induce cell cycle arrest at the G2/M phase in cancer cells 24‐26 …”

Section: Resultsmentioning

confidence: 99%

Efficacy of the novel tubulin polymerization inhibitor PTC‐028 for myelodysplastic syndrome

et al. 2020

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Monomer tubulin polymerize into microtubules, which are highly dynamic and play a critical role in mitosis. Therefore, microtubule dynamics are an important target for anticancer drugs. The inhibition of tubulin polymerization or depolymerization was previously targeted and exhibited efficacy against solid tumors. The novel small molecule PTC596 directly binds tubulin, inhibits microtubule polymerization, downregulates MCL‐1, and induces p53‐independent apoptosis in acute myeloid leukemia cells. We herein investigated the efficacy of PTC‐028, a structural analog of PTC596, for myelodysplastic syndrome (MDS). PTC‐028 suppressed growth and induced apoptosis in MDS cell lines. The efficacy of PTC028 in primary MDS samples was confirmed using cell proliferation assays. PTC‐028 synergized with hypomethylating agents, such as decitabine and azacitidine, to inhibit growth and induce apoptosis in MDS cells. Mechanistically, a treatment with PTC‐028 induced G2/M arrest followed by apoptotic cell death. We also assessed the efficacy of PTC‐028 in a xenograft mouse model of MDS using the MDS cell line, MDS‐L, and the AkaBLI bioluminescence imaging system, which is composed of AkaLumine‐HCl and Akaluc. PTC‐028 prolonged the survival of mice in xenograft models. The present results suggest a chemotherapeutic strategy for MDS through the disruption of microtubule dynamics in combination with DNA hypomethylating agents.

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MPT0B169 and MPT0B002, New Tubulin Inhibitors, Induce Growth Inhibition, G2/M Cell Cycle Arrest, and Apoptosis in Human Colorectal Cancer Cells

Cited by 6 publications

References 19 publications

Tubulin beta 4B chain is involved in the cell cycle process of mouse spermatogonia through CDK2

Tubulin beta 4B chain is involved in the cell cycle process of mouse spermatogonia through CDK2

miR-217 inhibits the migration and invasion of HeLa cells through modulating MAPK1

Efficacy of the novel tubulin polymerization inhibitor PTC‐028 for myelodysplastic syndrome

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