In vitro induction of mitotic catastrophe as a therapeutic approach for oral cancer using the ethanolic extract of Juniperus squamata

Abstract

Mitotic catastrophe, a cell death mechanism characterized by abnormal mitosis, has been regarded as a therapeutic approach for the development of anti-cancer drug candidates. The aim of the present study was to investigate the potential effect of the ethanolic extract of Juniperus squamata (EEJS) on the occurrence of mitotic catastrophe in human oral cancer cell lines. The effect of EEJS on the occurrence of mitotic catastrophe was evaluated by measuring cytotoxicity, observing phase-contrast or transmission electron microscope findings, evaluating the appearance of microtubule or chromosome abnormalities, and detecting the phosphorylation of histone H3 (Ser 10 ). The apoptotic effect of EEJS was assessed by detecting cleaved PARP, analyzing the sub-G 1 population, Annexin V-FITC/PI double staining, western blot analysis, and the transient transfection of myeloid cell leukemia-1 (Mcl-1) overexpression vectors. EEJS treatment was effective in inhibiting cell proliferation in human oral cancer cell lines. EEJS resulted in the enrichment of enlarged multinucleated cells, the disturbance of microtubule formation, and increased phosphorylation of histone H3 (Ser 10 ), which demonstrates the occurrence of mitotic catastrophe. Additionally, the multinucleated cells underwent apoptotic cell death in a cell context-dependent manner, which was associated with the reduction of Mcl-1 protein levels. Findings of the present study indicate that EEJS could be effective for treating human oral cancer by promoting mitotic catastrophe linked to apoptotic cell death.

Myeloid cell leukemia-1 expression in cancers of the oral cavity: a scoping review

“…Lycorine hydrochloride induced the mitochondria-mediated apoptosis pathway through the downregulation of Mcl-1 [75]. Treatment with Juniperus squamata induced a mitotic catastrophe, leading to apoptosis via Mcl-1 reduction in OSCC cell lines [76].…”

Podophyllotoxin reduces the aggressiveness of human oral squamous cell carcinoma through myeloid cell leukemia‑1

“…To identify the potent anticancer mechanism of action of PPT in OSCC, apoptosis associated with the Bcl-2 family of proteins, particularly myeloid cell leukemia-1 (Mcl-1) was assessed. In OSCC, the Mcl-1 gene is commonly amplified and upregulated, which affects the clinical course and survival of patients with this disease (21)(22)(23)(24). Mcl-1 is also upregulated and is associated with poor outcomes in other malignant tumors, such as hematologic malignancies (25), breast cancer (26,27), lung (28), and gastric cancer (29).…”

Podophyllotoxin enfeebles human oral squamous cell carcinoma through Myeloid cell leukemia-1

“…To identify the potent anticancer mechanism of action of PPT in OSCC, we examined apoptosis associated with the Bcl-2 family, particularly myeloid cell leukemia-1 (Mcl-1). In OSCC, the Mcl-1 gene is commonly ampli ed and upregulated, which affects the clinical course and patient survival [20][21][22][23].…”