Pseudolaric acid B inhibits neuroglioma cell proliferation through DNA damage response

Abstract

Human neuroglioma is one of the most common malignant intracranial tumors in neurosurgery, and accounts for more than 50% of all brain cancer cases. Thus, a clinically effective drug with which to treat neuroglioma is urgently required. Pseudolaric acid B (PAB), a diterpene acid isolated from the root and trunk bark of Pseudolarix kaempferi Gordon (Pinaceae), was found to inhibit cell growth in a variety of cancer cell lines, but to date the effect of PAB on neuroglioma remains unclear. MTT analysis confirmed that PAB inhibited neuroglioma A172 cell growth in a time- and dose-dependent manner. In addition, PAB influenced the aggregation of tubulin in A172 cells. Meanwhile following PAB treatment, a higher percentage of cells accumulated in the G2/M phase from 12 to 48 h, while at 36 h, cell cycle slippage into the G0/G1 phase, and at 48 h, slippage into the S phase was observed using flow cytometric analysis. Corresponding protein expression was consistent with the cell cycle alteration as detected by western blotting, and it was speculated that cell cycle slippage was related to reduced effectiveness of PAB which warrants further investigation. Meanwhile PAB induced cell death by regulating p38, ERK and JNK expression and activating the DNA damage response. Therefore, PAB plays an antitumor role in A172 cells, and may be a candidate drug for neuroglioma therapy.

Regulation of host factor γ-H2AX level and location by enterovirus A71 for viral replication

“…Hence, in this study, we investigated the location of γ-H2AX in the nucleus after infection with EVA71. We selected pseudolaric acid B (a diterpene acid) as a positive control because it induces the DDR [ 36 ]; subsequently, we extracted nuclear and cytoplasmic proteins for Western blotting analysis. The results showed that levels of γ-H2AX protein were increased in the nucleus at 36 h after treatment with 4 µM pseudolaric acid in RD cells ( Figure 3a ).…”

Pseudolaric acid B induces apoptosis in human rhabdomyosarcoma RD cells

“…PAB has been reported to target tubulin ( 20 , 21 ). Therefore, the current study investigated the effects of PAB on the microtubule networks of RD cells by tubulin immunofluorescence staining.…”

Effect of ingredients from Chinese herbs on enterovirus D68 production

“…Then, it was investigated that G2/M phase‐related drugs inhibited EVD68 production, it was found that pseudolaric acid B (Song et al, ; Wang et al, ), oridonin (Zheng et al, ), and erianin (Wang et al, ) did not affect intracellar viral protein expression although they had the trend to decrease the expression, therefore, it was speculated that the decreased trend was due to decreased viral mRNA level by pseudolaric acid B, oridonin, and erianin, respectively. Meanwhile, only oridonin affected supernatant viral protein expression, but all of them decreased supernatant viral genome level, and the fold difference in the TCID50/ml and the supernatant viral genome level between the control‐treated and pseudolaric acid B‐treated cells was 2.34 × 10 2 and 11.31, oridonin was 5.10 × 10 3 and 54.05, and erianin was 1.23 × 10 3 and 108.70, therefore, pseudolaric acid, oridonin, and erianin inhibiting viral genome packaged into virions partly explained the decreased production.…”

“…Then, it was investigated that G2/M phase-related drugs inhibited EVD68 production, it was found that pseudolaric acid B (Song et al, 2017;Wang et al, 2018), oridonin (Zheng et al, 2017), and erianin (Wang et al, 2016) did not affect intracellar viral protein expression although they had the trend to decrease the expression, therefore, it was speculated that the decreased trend was due to decreased viral mRNA level by pseudolaric acid B, oridonin, and erianin, respectively.…”