Cyclovirobuxine D inhibits cell proliferation and migration and induces apoptosis in human glioblastoma multiforme and low‑grade glioma

Abstract

Gliomas are the most common neoplasm of the human central nervous system. Glioblastoma multiforme (GBM) is one of the most serious types of gliomas. Although considerable progress has been made in the development of cancer therapeutic agents, several antineoplastic drugs fail to penetrate the blood-brain barrier (BBB), resulting in a low survival rate of glioma patients. Recent studies have revealed that the traditional Chinese medicine Buxus microphylla contains the main active component Cyclovirobuxine D (CVB-D), which can cross the BBB with a novel delivery system. However, it remains unclear whether CVB-D exerts anticancer effects against GBM and low-grade glioma (LGG). The aim of the present study was to explore the feasibility of CVB-D as a new effective agent in the treatment of GBM and LGG. The ability of CVB-D to inhibit GBM and LGG cell proliferation was detected by CCK8 assay. Flow cytometry was used to detect cell cycle progression and apoptosis induction by Annexin V-FITC/PI assay. The expression levels of the apoptosis-associated proteins, namely cleaved caspase-3 and Bax/Bcl-2, were detected by western blot analysis. The mitochondrial membrane potential (ΔΨm) was detected by Rh123 dyed fluorescence micrograph. Hoechst staining was used to observe the morphological characteristics of the apoptotic cells. The scratch test was used to evaluate the migration of GBM and LGG cells. The results indicated that CVB-D reduced cell viability of T98G and Hs683 cells. Flow cytometry demonstrated that CVB-D-treated cells were arrested at the S phase of their cell cycle. The expression levels of the apoptosis-associated proteins were increased in CVB-D-treated cells. Rh123 and Hoechst staining indicated morphological changes and mitochondrial membrane potential changes of the cells undergoing apoptosis. The data confirmed that CVB-D inhibited cell proliferation by arresting the cell cycle of GBM and LLG cells and that it promoted the induction of cell apoptosis by altering the mitochondrial membrane potential. The findings of the present study indicate the potential value of CVB-D in the treatment of glioma.

Cyclovirobuxine D, a cardiovascular drug from traditional Chinese medicine, alleviates inflammatory and neuropathic pain mainly via inhibition of voltage-gated Cav3.2 channels

“…Our study shows that CVB-D effectively and long-lastingly relieves PTX-induced thermal hypersensitivity ( Figure 8 ). This finding, in conjunction with recent reports of CVB-D’s promising in vitro and in vivo antiproliferative activities ( Wu et al, 2015 ; Jiang et al, 2020 ; Zhang et al, 2020 ; Zhou et al, 2020 ; Liu et al, 2021 ; Zeng et al, 2021 ), also raises the potential of an application of CVB-D in cancer treatment and chemotherapy: a combination of CVB-D and PTX may offer a promising opportunity to concurrently enhance the anticancer effect of PTX and reduce its unwanted neuropathic symptoms.…”

Identification of autophagic target RAB13 with small‐molecule inhibitor in low‐grade glioma via integrated multi‐omics approaches coupled with virtual screening of traditional Chinese medicine databases

“…However, the more detailed mechanism of cyclovirobuxine D to treat LGG has not been investigated. 52 In our study, we screened multi‐TCM databases and identified gallic acid as a novel potential RAB13 inhibitor, which was confirmed to negatively regulate autophagy as well as to induce cell death in SW1088 cells. Our study offers a new candidate TCM compound, gallic acid, to treat LGG with detailed mechanism—by inhibiting RAB13 and suppressing autophagy.…”

“…Recently, TCM cyclovirobuxine D, derived from Buxus microphylla, was reported to possess therapeutic potential on LGG through blocking cell cycle and activating apoptosis. However, the more detailed mechanism of cyclovirobuxine D to treat LGG has not been investigated 52 . In our study, we screened multi‐TCM databases and identified gallic acid as a novel potential RAB13 inhibitor, which was confirmed to negatively regulate autophagy as well as to induce cell death in SW1088 cells.…”

Pull the plug: Anti‐angiogenesis potential of natural products in gastrointestinal cancer therapy

“…Cyclovirobuxine D (CVB‐D) is the major active component of Buxus microphylla, which is mainly used in the treatment of cardiovascular and cerebrovascular diseases (Bian et al, 2021; Yu, Fang, Lü, Xu, & Lu, 2011). In recent years, more and more evidence has suggested that CVB‐D may have inhibitory effects on various tumors (Lu et al, 2014; Zeng et al, 2021; Zhou et al, 2020). Besides, CVB‐D inhibits CRC cell growth and decreases angiogenesis via the CTHRC1‐AKT/ERK‐Snail signaling pathway, especially microvasculature (Jiang et al, 2020).…”