Radiosensitization to X-ray radiation by telomerase inhibitor MST-312 in human hepatoma HepG2 cells

Wang, Yali; Sun, Chao; Mao, Aihong; Zhang, Xin; Zhou, Xin; Wang, Zhenhua; Zhang, Hong

doi:10.1016/j.lfs.2014.12.027

Cited by 11 publications

(3 citation statements)

References 35 publications

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“…37 Another study revealed that disturbances in telomerase function by the telomerase inhibitor MST-312 could enhance the radiosensitivity of HepG2 cells to x-ray irradiation by impairing HR (homologous recombination) repair processes. 38 For the first time, our study indicated that low doses of BIBR1532 significantly impaired the telomeres and destroyed the DNA damage-protecting roles of telomerase, thus enhancing IR-induced cell death.…”

Section: Discussionmentioning

confidence: 68%

BIBR1532, a Selective Telomerase Inhibitor, Enhances Radiosensitivity of Non-Small Cell Lung Cancer Through Increasing Telomere Dysfunction and ATM/CHK1 Inhibition

Ding

Cheng

Pang

et al. 2019

International Journal of Radiation Oncology*Biology*Physics

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This study demonstrated that low concentrations of BIBR1532 could induce disturbances in telomerase function and enhance radiosensitivity of non-small cell lung cancer cells without systemic toxicity in vitro and in vivo. Mechanistically, low concentrations of BIBR1532 enhanced Purpose: Telomerase is reactivated in non-small cell lung cancer (NSCLC), and it increases cell resistance to irradiation through protecting damaged telomeres and enhancing DNA damage repair. We investigated the radiosensitizing effect of BIBR1532, a highly selective telomerase inhibitor, and its corresponding mechanism in NSCLC. Methods and Materials: Cell proliferation, telomerase activity, and telomere dysfunction-induced foci were measured with CCK-8 assay, real-time fluorescent quantitative polymerase chain reaction, and immunofluorescence. The effect of BIBR1532 on the response of NSCLC cells to radiation was analyzed using clonogenic survival and xenograft tumor assays. Cell death and cell senescence induced by BIBR1532 or ionizing radiation (IR), or both, were detected with western blotting, flow cytometry, and senescence-association b-galactosidase staining assay.

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Section: Discussionmentioning

confidence: 68%

BIBR1532, a Selective Telomerase Inhibitor, Enhances Radiosensitivity of Non-Small Cell Lung Cancer Through Increasing Telomere Dysfunction and ATM/CHK1 Inhibition

Ding

Cheng

Pang

et al. 2019

International Journal of Radiation Oncology*Biology*Physics

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“…As discussed in the previous section for nontelomeric activities of telomerase, the role for telomerase in activities such a DNA damage response is potentially important to cellular immortalization and cancer development. Additionally, in line with other telomerase inhibitors, MST-312 was also found to sensitize cells to X-ray radiation (Wang et al 2015). This potential to exhibit short-term and longterm effects indicates that this telomerase inhibitor has significant promise for use as a molecular tool for studying and defining non-telomeric activities of telomerase.…”

Section: Mst-312mentioning

confidence: 61%

Telomerase: Much Understood, Much More Remains Ripe for Discovery

Steding

Verga²

2015

MRAJ

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Telomerase, the reverse transcriptase responsible for extending the ends of linear chromosomes, has been studied in depth for the past few decades. Its importance in processes from cellular lifespan to cancer has been well documented. More recently, it has been exploited as a potential therapeutic target for cancer. With the development of telomerase inhibitors deemed safe for human use, inhibition of telomerase has become a promising adjuvant therapy capable of improving the therapeutic outcomes of other drugs. It is within these studies that we now turn to find a new world of previously under-explored territory for telomerase. Telomerase inhibition has opened the door to new discoveries into how this enzyme functions and what additional effects it might be having in cellular activity and gene regulation. These new avenues of exploration have the potential to advance our understanding of molecular biology, cellular activity, and even cancer development and progression. This review will briefly highlight telomerase inhibitors in cancer therapeutics and the role they might be able to play in defining additional non-telomeric activities of telomerase.

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“…Currently, research on radiosensitizers has been conducted through the mechanisms of hypoxia, topoisomerases, microtubules and caspases. Numerous of these examinations have performed well in pre-clinical trials, but information needs to be provided on the safety and practicability of these approaches in clinical trials (25). from another point of view, DNA damage response is a determinant of cancer outcome after radiotherapy (26), and telomerase dysfunction in mice imparted a radiosensitivity syndrome correlated with accelerated mortality (19).…”

Section: Discussionmentioning

confidence: 99%

Zidovudine, abacavir and lamivudine increase the radiosensitivity of human esophageal squamous cancer cell lines

et al. 2016

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Telomerase is a type of reverse transcriptase that is overexpressed in almost all human tumor cells, but not in normal tissues, which provides an opportunity for radiosensitization targeting telomerase. Zidovudine, abacavir and lamivudine are reverse transcriptase inhibitors that have been applied in clinical practice for several years. We sought to explore the radiosensitization effect of these three drugs on human esophageal cancer cell lines. Eca109 and Eca9706 cells were treated with zidovudine, abacavir and lamivudine for 48 h before irradiation was administered. Samples were collected 1 h after irradiation. Clonal efficiency assay was used to evaluate the effect of the combination of these drugs with radiation doses of 2, 4, 6 and 8 Gy. DNA damage was measured by comet assay. Telomerase activity (TA) and relative telomere length (TL) were detected and evaluated by real-time PCR. Apoptosis rates were assessed by flow cytometric analysis. The results showed that all the drugs tested sensitized the esophageal squamous cell carcinoma (ESCC) cell lines to radiation through an increase in radiation-induced DNA damage and cell apoptosis, deregulation of TA and decreasing the shortened TL caused by radiation. Each of the drugs investigated (zidovudine, abacavir and lamivudine) could be used for sensitizing human esophageal cancer cell lines to radiation. Consequently, the present study supports the potential of these three drugs as therapeutic agents for the radiosensitization of esophageal squamous cell cancer.

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Radiosensitization to X-ray radiation by telomerase inhibitor MST-312 in human hepatoma HepG2 cells

Cited by 11 publications

References 35 publications

BIBR1532, a Selective Telomerase Inhibitor, Enhances Radiosensitivity of Non-Small Cell Lung Cancer Through Increasing Telomere Dysfunction and ATM/CHK1 Inhibition

BIBR1532, a Selective Telomerase Inhibitor, Enhances Radiosensitivity of Non-Small Cell Lung Cancer Through Increasing Telomere Dysfunction and ATM/CHK1 Inhibition

Telomerase: Much Understood, Much More Remains Ripe for Discovery

Zidovudine, abacavir and lamivudine increase the radiosensitivity of human esophageal squamous cancer cell lines

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