Targeting Telomerase and ATRX/DAXX Inducing Tumor Senescence and Apoptosis in the Malignant Glioma

Fan, Hueng-Chuen; Chen, Chuan-Mu; Chi, Ching-Shiang; Tsai, Jeng-Dau; Chiang, Kuo-Liang; Chang, Yu-Kang; Lin, Shinn-Zong; Harn, Horng-Jyh

doi:10.3390/ijms20010200

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Targeting Telomerase and ATRX/DAXX Inducing Tumor Senescence and Apoptosis in the Malignant Glioma

by

Hueng-Chuen Fan

^1,2,3

,

Chuan-Mu Chen

^2,4

,

Ching-Shiang Chi

¹,

Jeng-Dau Tsai

^5,6,

Kuo-Liang Chiang

^7,8,

Yu-Kang Chang

^1,2,3,

Shinn-Zong Lin

^9,10 and

Horng-Jyh Harn

^9,11,*

¹

Department of Pediatrics, Department of Medical research, Tungs’ Taichung Metroharbor Hospital, Wuchi, Taichung 435, Taiwan

²

Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan

³

Department of Rehabilitation, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 356, Taiwan

⁴

The iEGG and Animal Biotechnology Center, and Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan

⁵

School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan

⁶

Department of Pediatrics, Chung Shan Medical University Hospital, Taichung 402, Taiwan

⁷

Department of Pediatric Neurology, Kuang-Tien General Hospital, Taichung 433, Taiwan

⁸

Department of Nutrition, Hungkuang University, Taichung 433, Taiwan

⁹

Buddhist Tzu Chi Bioinnovation Center, Tzu Chi Foundation, Hualien 970, Taiwan

¹⁰

Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Hualien 970, Taiwan

¹¹

Department of Pathology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien 970, Taiwan

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Int. J. Mol. Sci. 2019, 20(1), 200; https://doi.org/10.3390/ijms20010200

Submission received: 12 December 2018 / Accepted: 2 January 2019 / Published: 8 January 2019

(This article belongs to the Special Issue Intracranial Malignancies: Molecular Insights and Therapeutic Advances)

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Abstract

Glioblastoma multiforme (GBM) is a type of brain tumor that is notorious for its aggressiveness and invasiveness, and the complete removal of GBM is still not possible, even with advanced diagnostic strategies and extensive therapeutic plans. Its dismal prognosis and short survival time after diagnosis make it a crucial public health issue. Understanding the molecular mechanisms underlying GBM may inspire novel and effective treatments against this type of cancer. At a molecular level, almost all tumor cells exhibit telomerase activity (TA), which is a major means by which they achieve immortalization. Further studies show that promoter mutations are associated with increased TA and stable telomere length. Moreover, some tumors and immortalized cells maintain their telomeres with a telomerase-independent mechanism termed the “alternative lengthening of telomeres” (ALT), which relates to the mutations of the α-thalassemia/mental retardation syndrome X-linked protein (ATRX), the death-domain associated protein (DAXX) and H3.3. By means of the mutations of the telomerase reverse transcriptase (TERT) promoter and ATRX/DAXX, cancers can immortalize and escape cell senescence and apoptosis. In this article, we review the evidence for triggering GBM cell death by targeting telomerase and the ALT pathway, with an extra focus on a plant-derived compound, butylidene phthalide (BP), which may be a promising novel anticancer compound with good potential for clinical applications.

Keywords: glioblastoma multiforme (GBM) 2; telomerase 3; alternative lengthening of telomeres 4; α-thalassemia/mental retardation syndrome X-linked protein (ATRX) 5; death-domain associated protein (DAXX) 5; butylidene phthalide (BP)

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MDPI and ACS Style

Fan, H.-C.; Chen, C.-M.; Chi, C.-S.; Tsai, J.-D.; Chiang, K.-L.; Chang, Y.-K.; Lin, S.-Z.; Harn, H.-J. Targeting Telomerase and ATRX/DAXX Inducing Tumor Senescence and Apoptosis in the Malignant Glioma. Int. J. Mol. Sci. 2019, 20, 200. https://doi.org/10.3390/ijms20010200

AMA Style

Fan H-C, Chen C-M, Chi C-S, Tsai J-D, Chiang K-L, Chang Y-K, Lin S-Z, Harn H-J. Targeting Telomerase and ATRX/DAXX Inducing Tumor Senescence and Apoptosis in the Malignant Glioma. International Journal of Molecular Sciences. 2019; 20(1):200. https://doi.org/10.3390/ijms20010200

Chicago/Turabian Style

Fan, Hueng-Chuen, Chuan-Mu Chen, Ching-Shiang Chi, Jeng-Dau Tsai, Kuo-Liang Chiang, Yu-Kang Chang, Shinn-Zong Lin, and Horng-Jyh Harn. 2019. "Targeting Telomerase and ATRX/DAXX Inducing Tumor Senescence and Apoptosis in the Malignant Glioma" International Journal of Molecular Sciences 20, no. 1: 200. https://doi.org/10.3390/ijms20010200

APA Style

Fan, H.-C., Chen, C.-M., Chi, C.-S., Tsai, J.-D., Chiang, K.-L., Chang, Y.-K., Lin, S.-Z., & Harn, H.-J. (2019). Targeting Telomerase and ATRX/DAXX Inducing Tumor Senescence and Apoptosis in the Malignant Glioma. International Journal of Molecular Sciences, 20(1), 200. https://doi.org/10.3390/ijms20010200

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Targeting Telomerase and ATRX/DAXX Inducing Tumor Senescence and Apoptosis in the Malignant Glioma

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