Zoledronic acid significantly enhances radiation-induced apoptosis against human fibrosarcoma cells by inhibiting radioadaptive signaling

The effects of flavonoids from Korean Scutellaria baicalensis on fibrosarcoma HT1080 cells and their underlying molecular mechanism were investigated in this study. Flavonoids affected HT1080 cell proliferation by interrupting cell cycle progress, obviously augmenting the proportion of sub-G1 and diminishing that of G1 phase, and undergoing apoptosis at the tested dosage (100–400 μg/mL). In addition, the mediated apoptosis was mainly caused by total reactive oxygen species (ROS) generation and by up-regulating the ratio of Bax/Bcl-xL, triggering caspase cascades (caspase-3, -9 and -8), and inactivating PARP, dose-dependently. The proteomics results showed that AP-4, ARID 5B, HNRNP K, PLOG, Prdx6, and myosin-1, associated with cell growth, differentiation and development, and overexpressed in gastric cancer, colorectal cancer, pancreatic cancer, etc., were statistically down-regulated after the flavonoids treatment. Taken together, our data demonstrated that flavonoids from Korean S. baicalensis induced apoptosis in HT1080 cells, which involved a hierarchy of cellular pathways and multiple signal proteins, and might be a potential anticancer therapeutic agent.

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4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication

Scientific Reports ◽

10.1038/s41598-021-87850-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ryo Saga ◽

Yusuke Matsuya ◽

Rei Takahashi ◽

Kazuki Hasegawa ◽

Hiroyuki Date ◽

...

Keyword(s):

Intercellular Communication ◽

Dose Range ◽

Synthesis Inhibitor ◽

X Ray ◽

Tumour Control ◽

Synergetic Effects ◽

Fibrosarcoma Cells ◽

Oxidative Stress Level ◽

Human Fibrosarcoma Cells

AbstractHyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU) is a candidate of radiosensitizers which enables both anti-tumour and anti-metastasis effects in X-ray therapy. The curative effects under such 4-MU administration have been investigated in vitro; however, the radiosensitizing mechanisms remain unclear. Here, we investigated the radiosensitizing effects under 4-MU treatment from cell experiments and model estimations. We generated experimental surviving fractions of human fibrosarcoma cells (HT1080) after 4-MU treatment combined with X-ray irradiation. Meanwhilst, we also modelled the pharmacological effects of 4-MU treatment and theoretically analyzed the synergetic effects between 4-MU treatment and X-ray irradiation. The results show that the enhancement of cell killing by 4-MU treatment is the greatest in the intermediate dose range of around 4 Gy, which can be reproduced by considering intercellular communication (so called non-targeted effects) through the model analysis. As supposed to be the involvement of intercellular communication in radiosensitization, the oxidative stress level associated with reactive oxygen species (ROS), which leads to DNA damage induction, is significantly higher by the combination of 4-MU treatment and irradiation than only by X-ray irradiation, and the radiosensitization by 4-MU can be suppressed by the ROS inhibitors. These findings suggest that the synergetic effects between 4-MU treatment and irradiation are predominantly attributed to intercellular communication and provide more efficient tumour control than conventional X-ray therapy.

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