Vitamin K4 inhibits the proliferation and induces apoptosis of U2OS osteosarcoma cells via mitochondrial dysfunction

Di,Weihua; Khan,Muhammad; Gao,Yong; Cui,Jing; Wang,Deqiang; Qu,Mingfen; Feng,Liangtao; Maryam,Amara; Gao,Hongwen

doi:10.3892/mmr.2016.6001

Vitamin K4 inhibits the proliferation and induces apoptosis of U2OS osteosarcoma cells via mitochondrial dysfunction

Authors:
- Weihua Di
- Muhammad Khan
- Yong Gao
- Jing Cui
- Deqiang Wang
- Mingfen Qu
- Liangtao Feng
- Amara Maryam
- Hongwen Gao
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Affiliations: Department of Pain Treatment, Binzhou Medical University Affiliated Hospital, Binzhou, Shandong 256600, P.R. China, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116041, P.R. China, Department of Pathology, Jilin University Bethune Second Hospital, Changchun, Jilin 130041, P.R. China
Published online on: December 7, 2016 https://doi.org/10.3892/mmr.2016.6001
Pages: 277-284

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Abstract

Vitamin K (VK) is a group of fat‑soluble vitamins, which serve important roles in blood coagulation and bone metabolism. A recent study reported that several VK subtypes possess antitumor properties, however the antitumor effects of VK in osteosarcoma are unknown. The present study aimed to identify the antitumor effects of VK in osteosarcoma and the possible underlying mechanism of action. The effect of VK4 on cell viability was determined using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay. Cellular and nuclear morphological changes were observed by phase contrast microscopy. Cell cycle analysis, apoptotic rate, mitochondrial membrane potential and levels of reactive oxygen species (ROS) were detected by flow cytometry. In vitro cancer cell migration activities were evaluated using a Wound healing assay and Transwell microplates. The results demonstrated that VK4 arrested the cells in S phase and induced apoptosis. Additional mechanistic studies indicated that the induction of apoptosis by VK4 was associated with the increased production of reactive oxygen species, dissipation of the mitochondrial membrane potential, decreased Bcl‑2 family protein expression levels and activation of caspase‑3. In conclusion, the results suggest that the sensitivity of U2OS osteosarcoma cells to VK4 may be as a result of mitochondrial dysfunction. As it is readily available for human consumption, VK4 may therefore present a novel therapeutic candidate for the treatment of patients with osteosarcoma.

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