Deacetylisovaltratum disrupts microtubule dynamics and causes G2/M-phase arrest in human gastric cancer cells in vitro

Abstract

Aim:Deacetylisovaltratum (DI) is isolated from the traditional Chinese herbal medicine Patrinia heterophylla Bunge, which exhibits anti-cancer activity. Here, we investigated the effects of DI on human gastric carcinoma cell lines in vitro and elucidated its anti-cancer mechanisms.Methods:Human gastric carcinoma AGS and HGC-27 cell lines were treated with DI, and cell viability was detected with MTT assay. Cell cycle stages, apoptosis and mitochondrial membrane potential were measured using flow cytometry. Protein levels were analyzed by Western blotting. Tubulin polymerization assays and immunofluorescence were used to characterize the tubulin polymerization process.Results:DI inhibited the cell viability of AGS and HGC-27 cells in a dose- and time-dependent manner with IC50 values of 12.0 and 28.8 μmol/L, respectively, at 24 h of treatment. Treatment with DI (10–100 μmol/L) dose-dependently promoted tubulin polymerization, and induced significant G2/M cell cycle arrest in AGS and HGC-27 cells. Moreover, DI treatment disrupted mitochondrial membrane potential and induced caspase-dependent apoptosis in AGS and HGC-27 cells.Conclusion:DI induces G2/M-phase arrest by disrupting tubulin polymerization in human gastric cancer cells, which highlights its potent anti-cancer activity and potential application in gastric cancer therapy.

Bioinformatic analysis identifies potentially key differentially expressed genes in oncogenesis and progression of clear cell renal cell carcinoma

“…MELK is an oncogenic kinase essential for early recurrence of hepatocellular carcinoma (Xia et al, 2016). Studies have shown that MELK is a novel biomarker and a potential therapeutic target in cervical cancer (Lv et al, 2018), triple-negative breast cancer (Moreno, 2016) and gastric cancer (Zhang et al, 2016a). NDC80 (Nuclear division cycle 80) is also known as highly expressed in cancer 1 (HEC1).…”

Integrated Protein–Protein Interaction and Weighted Gene Co-expression Network Analysis Uncover Three Key Genes in Hepatoblastoma

“…The molecular function analysis revealed that genes in the blue module were enriched for the tubulin binding, microtubule binding, and microtubule motor activity pathways. Disrupted microtubule dynamics have previously been reported to modulate cell proliferation in several human tumors, including hepatocellular carcinoma (HCC) (Zhang et al, 2016;Aboubakr et al, 2017). The cellular component analysis revealed that genes in the blue module were predominantly associated with spindle, kinetochore, and mitotic spindle cellular components, which serve essential functions during mitosis (Sharp et al, 2000).…”

Emerging Potential of Naturally Occurring Molecules against Gastric Cancer: Insights Molecular Mechanism and Therapeutic Targets

“…Deacetylisovaltratum, extracted from Patrinia heterophylla Bunge. (Caprifoliaceae, was treated to AGS and HGC-27 human gastric cancer cell lines for 24 h at the dose of 4, 8, 16 μM/mL and 10, 20, 30 μM/mL, respectively [60]. Deacetylisovaltratum induced mitochondrial and caspase-dependent apoptosis.…”

“…(Gentianaceae) induced S phase cell cycle arrest [39,40,77,82]. Deacetylisovaltratum, Euphorbia lunulate (Euphorbiaceae) extract, phloretin, trifolirhizin, and tanshinone IIA triggered G2/M phase cell cycle arrest [44,46,55,60,76]. Jinlong Capsule halted the cell cycle in S and G2/M phase [89].…”