Abstract-Effective demethylation of melanoma cells using terahertz radiation

Hwayeong Cheon, Hee-Jin Yang, Moran Choi, and Joo-Hiuk Son

 Schematic showing THz demethylation using resonant THz radiation system. High-power THz radiation was generated using a regenerative amplifier and LiNbO3 crystal. The THz filter limited the THz bandwidth to around the resonance frequency of the methyl-DNA bonds.

https://www.osapublishing.org/boe/abstract.cfm?uri=boe-10-10-4931

Terahertz (THz) demethylation is a photomedical technique applied to dissociate methyl-DNA bonds and reduce global DNA methylation using resonant THz radiation. We evaluated the performance of THz demethylation and investigated the DNA damage caused by THz irradiation. The demethylation rate in M-293T DNA increased linearly with the irradiation power up to 48%. The degree of demethylation increased with exposure to THz radiation, saturating after 10 min. Although THz demethylation occurred globally, most of the demethylation occurred within the partial genes in the CpG islands. Subsequently, we performed THz demethylation of melanoma cells. The degree of methylation in the melanoma cell pellets decreased by approximately 10–15%, inducing ∼5–8 abasic sites per 105 bp; this was considerably less than the damaged DNA irradiated by the high-power infrared laser beam used for generating THz pulses. These results provide initial data for THz demethylation and demonstrate the applicability of this technique in advanced cancer cell research. THz demethylation has the potential to develop into a therapeutic procedure for cancer, similar to that involving chemical demethylating agents.

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Abstract-Detection and manipulation of methylation in blood cancer DNA using terahertz radiation

Hwayeong Cheon, Jin Ho Paik, Moran Choi, Hee-Jin Yang,  Joo-Hiuk Son

https://www.nature.com/articles/s41598-019-42855-x

DNA methylation is a pivotal epigenetic modification of DNA that regulates gene expression. Abnormal regulation of gene expression is closely related to carcinogenesis, which is why the assessment of DNA methylation is a key factor in cancer research. Terahertz radiation may play an important role in active demethylation for cancer therapy because the characteristic frequency of the methylated DNA exists in the terahertz region. Here, we present a novel technique for the detection and manipulation of DNA methylation using terahertz radiation in blood cancer cell lines. We observed the degree of DNA methylation in blood cancer at the characteristic resonance of approximately 1.7 THz using terahertz time-domain spectroscopy. The terahertz results were cross-checked with global DNA methylation quantification using an enzyme-linked immunosorbent assay. We also achieved the demethylation of cancer DNA using high-power terahertz radiation at the 1.7-THz resonance. The demethylation degrees ranged from 10% to 70%, depending on the type of cancer cell line. Our results show the detection of DNA methylation based on the terahertz molecular resonance and the manipulation of global DNA methylation using high-power terahertz radiation. Terahertz radiation may have potential applications as an epigenetic inhibitor in cancer treatment, by virtue of its ability to induce DNA demethylation, similarly to decitabine.

Abstract-Toward clinical cancer imaging using terahertz spectroscopy

Hwayeong Cheon ; Hee-Jin Yang ;  Joo-Hiuk Son

http://ieeexplore.ieee.org/document/7929316/

Cancer imaging using terahertz (THz) electromagnetic waves has the potential to overcome the drawbacks of existing cancer imaging techniques because of the unique properties of THz radiation. It is non-ionizing, highly sensitive to water molecules, and suitable for the observation of many biomolecular characteristics based on low-energy vibrational modes. Consequently, it is advantageous to use THz cancer imaging for detection, especially of superficial carcinomas in soft tissues. However, there are three primary challenges facing this type of cancer imaging that must be addressed before it can be applied medically: the limited penetration depth in hydrated tissues, the difficulty of obtaining molecular resonance fingerprints of cancers, and the low image contrast between tissues. These challenges can be overcome by applying several state-of-the-art techniques; the penetration depth has been enhanced sufficiently to observe cancer lesions deep inside tissues by using freezing and penetration-enhancing agents: the biochemical modification of DNA can be utilized to track the resonance fingerprints of carcinogenesis at the genomic DNA level; and nanoparticles can increase the THz imaging contrast if they are employed similarly to how they are used in magnetic resonance imaging. These solutions are important to enable THz cancer imaging to be performed in clinical settings.

Abstract-Terahertz molecular resonance of cancer DNA

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• Hwayeong Cheon
• , Hee-jin Yang
• , Sang-Hun Lee
• , Young A Kim
•  & Joo-Hiuk Son

http://www.nature.com/articles/srep37103

Carcinogenesis involves the chemical and structural alteration of biomolecules in cells. Aberrant methylation of DNA is a well-known carcinogenic mechanism and a common chemical modification of DNA. Terahertz waves can directly observe changes in DNA because the characteristic energies lie in the same frequency region. In addition, terahertz energy levels are not high enough to damage DNA by ionization. Here, we present terahertz molecular resonance fingerprints of DNA methylation in cancer DNA. Methylated cytidine, a nucleoside, has terahertz characteristic energies that give rise to the molecular resonance of methylation in DNA. Molecular resonance is monitored in aqueous solutions of genomic DNA from cancer cell lines using a terahertz time-domain spectroscopic technique. Resonance signals can be quantified to identify the types of cancer cells with a certain degree of DNA methylation. These measurements reveal the existence of molecular resonance fingerprints of cancer DNAs in the terahertz region, which can be utilized for the early diagnosis of cancer cells at the molecular level.