Blue LED causes cell death in human hepatoma by inducing DNA damage

Abstract Phototherapies, including sunlight, infrared, ultraviolet, visible and laser, parts of which present high curative effect, small invasion, and negligible adverse reactions in cancer treatment. Here we aimed to explore the potential therapeutical effects of blue LED in hepatoma cell and decipher the underlying cellular/molecular mechanisms. We demonstrated that the irradiation of blue LED light in hepatoma cell could lead to cell proliferation reduction along with the cell apoptosis increase. Simultaneously, blue LED irradiation also markedly suppressed the migration and invasion ability of hepatoma cells. Sphere formation analysis further revealed the decreased stemness of hepatoma cell under the treatment of blue LED irradiation. In addition, blue LED irradiation significantly promoted the expression of γ-H2AX, a sensitive molecular marker of DNA damage. Collectively, we demonstrated that blue LED irradiation exhibited anti-tumor effects on liver cancer by inducing DNA damage, representing a potential approach for human hepatoma treatment.

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Antioxidant supplements promote tumor formation and growth and confer drug resistance in hepatocellular carcinoma by reducing intracellular ROS and induction of TMBIM1

Cell & Bioscience ◽

10.1186/s13578-021-00731-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Vanilla Xin Zhang ◽

Karen Man-Fong Sze ◽

Lo-Kong Chan ◽

Daniel Wai-Hung Ho ◽

Yu-Man Tsui ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatoma Cell ◽

Tumor Formation ◽

In Vitro Assays ◽

Migration And Invasion ◽

Intracellular Ros ◽

Antioxidant Supplements ◽

Sphere Formation

Abstract Background Controversy over the benefits of antioxidants supplements in cancers persists for long. Using hepatocellular carcinoma (HCC) as a model, we investigated the effects of exogenous antioxidants N-acetylcysteine (NAC) and glutathione (GSH) on tumor formation and growth. Methods Multiple mouse models, including diethylnitrosamine (DEN)-induced and Trp53KO/C-MycOE-induced HCC models, mouse hepatoma cell and human HCC cell xenograft models with subcutaneous or orthotopic injection were used. In vitro assays including ROS assay, colony formation, sphere formation, proliferation, migration and invasion, apoptosis, cell cycle assays were conducted. Western blot was performed for protein expression and RNA-sequencing to identify potential gene targets. Results In these multiple different mouse and cell line models, we observed that NAC and GSH promoted HCC tumor formation and growth, accompanied with significant reduction of intracellular reactive oxygen species (ROS) levels. Moreover, NAC and GSH promoted cancer stemness, and abrogated the tumor-suppressive effects of Sorafenib both in vitro and in vivo. Exogenous supplementation of NAC or GSH reduced the expression of NRF2 and GCLC, suggesting the NRF2/GCLC-related antioxidant production pathway might be desensitized. Using transcriptomic analysis to identify potential gene targets, we found that TMBIM1 was significantly upregulated upon NAC and GSH treatment. Both TCGA and in-house RNA-sequence databases showed that TMBIM1 was overexpressed in HCC tumors. Stable knockdown of TMBIM1 increased the intracellular ROS; it also abolished the promoting effects of the antioxidants in HCC cells. On the other hand, BSO and SSA, inhibitors targeting NAC and GSH metabolism respectively, partially abrogated the pro-oncogenic effects induced by NAC and GSH in vitro and in vivo. Conclusions Our data implicate that exogenous antioxidants NAC and GSH, by reducing the intracellular ROS levels and inducing TMBIM expression, promoted HCC formation and tumor growth, and counteracted the therapeutic effect of Sorafenib. Our study provides scientific insight regarding the use of exogenous antioxidant supplements in cancers.

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A standardized extract from Paeonia lactiflora and Astragalus membranaceus induces apoptosis and inhibits the proliferation, migration and invasion of human hepatoma cell lines

International Journal of Oncology ◽

10.3892/ijo.2013.2085 ◽

2013 ◽

Vol 43 (5) ◽

pp. 1643-1651 ◽

Cited By ~ 16

Author(s):

JING-JING WU ◽

WU-YI SUN ◽

SHAN-SHAN HU ◽

SEN ZHANG ◽

WEI WEI

Keyword(s):

Cell Lines ◽

Hepatoma Cell ◽

Astragalus Membranaceus ◽

Migration And Invasion ◽

Human Hepatoma ◽

Paeonia Lactiflora ◽

Human Hepatoma Cell ◽

Hepatoma Cell Lines

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Performance of high-throughput CometChip assay using primary human hepatocytes: a comparison of DNA damage responses with in vitro human hepatoma cell lines

Archives of Toxicology ◽

10.1007/s00204-020-02736-z ◽

2020 ◽

Vol 94 (6) ◽

pp. 2207-2224 ◽

Cited By ~ 3

Author(s):

Ji-Eun Seo ◽

Qiangen Wu ◽

Matthew Bryant ◽

Lijun Ren ◽

Qiang Shi ◽

...

Keyword(s):

Dna Damage ◽

Cell Lines ◽

High Throughput ◽

Hepatoma Cell ◽

Human Hepatocytes ◽

Human Hepatoma ◽

Human Hepatoma Cell ◽

Hepatoma Cell Lines ◽

Dna Damage Responses

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The Different Induction Mechanisms of Growth Arrest DNA Damage Inducible Gene 45 ß in Human Hepatoma Cell Lines

Chemotherapy ◽

10.1159/000338386 ◽

2012 ◽

Vol 58 (2) ◽

pp. 165-174 ◽

Cited By ~ 5

Author(s):

Varun Seewoo ◽

Weiping Yang ◽

Hailei Du ◽

Jiayu Wang ◽

Andy Lin ◽

...

Keyword(s):

Dna Damage ◽

Cell Lines ◽

Hepatoma Cell ◽

Growth Arrest ◽

Human Hepatoma ◽

Human Hepatoma Cell ◽

Hepatoma Cell Lines ◽

Inducible Gene

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Hedgehog Signal Inhibitor GANT61 Inhibits the Malignant Behavior of Undifferentiated Hepatocellular Carcinoma Cells by Targeting Non-Canonical GLI Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms21093126 ◽

2020 ◽

Vol 21 (9) ◽

pp. 3126

Author(s):

Kensuke Harada ◽

Ryuya Ohashi ◽

Kyoko Naito ◽

Keita Kanki

Keyword(s):

Hepatocellular Carcinoma ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Hepatoma Cell ◽

Mek Inhibitor ◽

Specific Expression ◽

Mesenchymal Transition ◽

Hepatoma Cell Lines ◽

And Migration ◽

Sphere Formation

The Hedgehog (HH)–GLI pathway plays an important role in cell dedifferentiation and is therefore pivotally involved in the malignant transformation of cancer cells. GANT61, a selective inhibitor of GLI1 and GLI2, was reported as a promising treatment for cancer in various tissues; however, the biological impact of GANT61 in hepatocellular carcinoma (HCC), especially in undifferentiated HCC cells, remains unclear. In this study, we investigated the antitumor effect of GANT61 using two undifferentiated hepatoma cell lines: HLE and HLF. Quantitative PCR and RT-PCR analyses revealed that these cells express GLI transcripts, showing mesenchymal phenotypes characterized by the loss of epithelial and hepatic markers and specific expression of epithelial–mesenchymal transition (EMT)-related genes. GANT61 significantly reduced the proliferation and cell viability after drug treatment using 5-FU and Mitomycin C. We showed that GLI transcript levels were down-regulated by the MEK inhibitor U0126 and the Raf inhibitor sorafenib, suggesting that non-canonical signaling including the Ras–Raf–MEK–ERK pathway is involved. Sphere formation and migration were significantly decreased by GANT61 treatment, and it is suggested that the underlying molecular mechanisms are the down-regulation of stemness-related genes (Oct4, Bmi1, CD44, and ALDH) and the EMT-related gene Snail1. The data presented here showed that direct inhibition of GLI might be beneficial for the treatment of dedifferentiated HCC.

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Nobiletin Inhibits Cell Growth, Migration and Invasion, and Enhances the Anti-Cancer Effect of Gemcitabine on Pancreatic Cancer Cells

Natural Product Communications ◽

10.1177/1934578x211004062 ◽

2021 ◽

Vol 16 (4) ◽

pp. 1934578X2110040

Author(s):

Xiang Ren ◽

Yuran Ma ◽

Xiao Wang ◽

Xuetao Xu ◽

Panpan Wu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Biological Activities ◽

Inhibitory Effect ◽

Migration And Invasion ◽

Pancreatic Cancer Cells ◽

Underlying Mechanisms ◽

Sphere Formation

Natural products are very promising adjuvants with a variety of biological activities. Nobiletin, a citrus polymethoxyflavone, has been shown to exert an anticancer effect in various cell lines. In this study, we investigated the effects of nobiletin on cell viability, sphere formation, migration and invasion of pancreatic cancer cells, and the underlying mechanisms. Our results demonstrate that nobiletin significantly inhibited PANC-1 cell migration and invasion, and these effects were associated with downregulation of MMP-2. We also found that nobiletin, in a low concentration, exhibited a strong inhibitory effect on sphere formation. The potential molecular mechanisms were related to significant downregulation of p-mTOR and p-STAT3. Furthermore, we found that nobiletin combined with gemcitabine synergistically inhibited PANC-1 cell viability and sphere formation. The underlying mechanisms of the synergistic inhibition on growth were associated with decreases in p-STAT3 expression. Overall, our results suggest that nobiletin may be a promising candidate for pancreatic cancer adjuvant treatment.

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