Anti-Proliferative and Apoptosis-Inducing Effect of Theabrownin against Non-small Cell Lung Adenocarcinoma A549 Cells

Wu, Feifei; Zhou, Li; Jin, Wangdong; Yang, W.; Wáng, Ying; Yan, Bo; Du, Wei; Zhang, Qiang; Zhang, Lei; Guo, Yonghua; Zhang, Jin; Shan, Letian; Efferth, Thomas

doi:10.3389/fphar.2016.00465

Cited by 32 publications

(28 citation statements)

References 41 publications

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“…Apart from polyphenols, TB attracts increasing attention in recent years due to its bioactivities and therapeutic potential . In our previous studies, TB exerted strong pro‐apoptotic effects against non‐small cell lung cancer via the p53 signalling pathway . Using xenograft model and osteosarcoma cells, this study investigated the anti‐OS effects and molecular mechanism of TB.…”

Section: Discussionmentioning

confidence: 96%

“…TB comprises of a family of macromolecules transformed from polyphenols, and is considered superior to TF or TR in physicochemical and medicinal properties. Previously, we reported that TB possessed strong pro‐apoptotic and cell cycle arresting effects on human carcinoma cells, making it a promising candidate for cancer therapy . To determine its anti‐OS effect, this study employed U2OS cells and performed in vivo and in vitro assays.…”

Section: Introductionmentioning

confidence: 99%

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Theabrownin triggers DNA damage to suppress human osteosarcoma U2OS cells by activating p53 signalling pathway

Jin

Zhou

Yan

et al. 2018

J Cellular Molecular Medi

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Osteosarcoma becomes the second leading cause of cancer death in the younger population. Current outcomes of chemotherapy on osteosarcoma were unsatisfactory to date, demanding development of effective therapies. Tea is a commonly used beverage beneficial to human health. As a major component of tea, theabrownin has been reported to possess anti‐cancer activity. To evaluate its anti‐osteosarcoma effect, we established a xenograft model of zebrafish and employed U2OS cells for in vivo and in vitro assays. The animal data showed that TB significantly inhibited the tumour growth with stronger effect than that of chemotherapy. The cellular data confirmed that TB‐triggered DNA damage and induced apoptosis of U2OS cells by regulation of Mki67, PARP, caspase 3 and H2AX, and Western blot assay showed an activation of p53 signalling pathway. When P53 was knocked down by siRNA, the subsequent downstream signalling was blocked, indicating a p53‐dependent mechanism of TB on U2OS cells (p53 wt). Using osteosarcoma cell lines with p53 mutations (HOS, SAOS‐2 and MG63), we found that TB exerted stronger inhibitory effect on U2OS cells than that on p53‐mut cell lines, but it also exerted obvious effect on SAOS‐2 cells (p53 null), suggesting an activation of p53‐independent pathway in the p53‐null cells. Interestingly, theabrownin was found to have no toxicity on normal tissue in vivo and could even increase the viability of p53‐wt normal cells. In sum, theabrownin could trigger DNA damage and induce apoptosis on U2OS cells via a p53‐dependent mechanism, being a promising candidate for osteosarcoma therapy.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Theabrownin triggers DNA damage to suppress human osteosarcoma U2OS cells by activating p53 signalling pathway

Jin

Zhou

Yan

et al. 2018

J Cellular Molecular Medi

Self Cite

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“…In our previous studies, we have reported that DNA damage induction was associated with P53 pathway-mediated pro-apoptotic mechanism of theabrownin ( Wu et al, 2016 ; Jin et al, 2018 ). However, although both TF and theabrownin activated P53 pathway and induced tumor cell apoptosis, we did not find DNA damage induction with TF treatment in this study.…”

Section: Discussionmentioning

confidence: 97%

Theaflavin Induces Apoptosis of A375 Human Melanoma Cells and Inhibits Tumor Growth in Xenograft Zebrafishes Through P53- and JNK-Related Mechanism

et al. 2020

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Theaflavin (TF) is a major active pigment and polyphenol of tea, possessing anti-cancer activities. However, little is known about its activity and mechanism on melanoma cells. To fill this gap, we conducted in vitro experiments (cell viability assay, morphology observation, DAPI staining, and flow cytometry) and in vivo experiment by using a xenograft model of larval zebrafishes. Real-time PCR (qPCR) and Western blot (WB) analyses were conducted to explore the mechanism of TF. The in vitro data showed that TF exerted significant anti-proliferative and pro-apoptotic effects on A375 cells in a concentration-dependent manner. In vivo , TF significantly inhibited A375 tumor growth in larval zebrafishes at 0.67 and 2.0 μg/ml (1.3 to 3.9 μM). qPCR and WB data showed that TF significantly activated the P53 pathway-related proteins (ATM, CHK1/2, P53, and CASP8/3) and the JNK pathway-related proteins (ASK1, JNK, and C-JUN) through phosphorylation and cleavage, followed by activation of pro-apoptotic molecules (PARP, BAX , BIM , PUMA , and P53 ). In sum, TF possessed cytotoxic pro-apoptotic and tumor-inhibitory effects on A375 cells through activations of P53 and JNK pathways. This is the first report on TF regarding its effects and mechanism on A375 cells, making it a promising candidate of natural products for clinical treatment of melanoma.

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“…Several research groups have indicated that cell growth encourages cell survival and decreases the opportunity for cell death or apoptosis (47)(48)(49)(50)(51)(52). Based on differences in G1 and S between HCC 1806 and L133 TK1-/-, we propose that TK1 may be influencing cell cycle transitions, specifically S to G2.…”

Section: Exploring Factors In Invasion Apoptosis and Progressionmentioning

confidence: 93%

TK1 in Cancer Progression: elucidating its influence on cellular invasion and survival

Bitter

Townsend

Tsai

et al. 2019

Preprint

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1. Background: The salvage pathway enzyme thymidine kinase 1 (TK1) is elevated in the serum of several different cancer types and higher expression is associated with more aggressive tumor grade. As a result, it has potential as a biomarker for diagnosis and prognosis. Recent studies indicate that TK1 may be involved in cancer pathogenesis; however, its direct involvement has not been identified. We propose to evaluate the effects of TK1 on cancer progression in vitro through measuring cellular invasion and survival of breast cancer cells.2.Methods: Breast cancer cells MDA-MB-231, HCC 1806, and MCF7 were cultured according to standard techniques. We employed the use of TK1 target siRNA and a CRISPR-Cas9 TK1 knockout plasmid to compare transfected cell lines to wild type cell lines. Protein factors in survival and invasive pathways were also tested for correlations to TK1 in BRCA RNA-seq patient data (n=1095) using the TIMER program. Cellular invasion was quantified in cell index (factor of impedance) over a 24-hour period. Cell survival was measured by apoptosis under metabolic and DNA stress using flow cytometry. All results were statistically assessed using an ANOVA or t-test in GraphPad PRISM®.3.Results: Cellular invasion assays assessing wild type and TK1 knockdown/knockout (TK1-/-) cell types showed TK1-/- cell lines had increased invasion potential (p= 0.0001). Bioinformatically, we saw a strong overall negative correlation between apoptotic factors and TK1 (p ≤ 0.05). When testing TK1 effects on cell survival we saw a protective affect under DNA stress (p ≤ 0.05), but not under metabolic stress (p= 0.0001).4.Conclusion From cell cycle analysis, we observed a shift towards S phase in TK1-/- cells. This shift to S phase would promote growth and account for the increased cellular invasion and decrease in metabolic induced stress in TK1-/- cells. We propose that cancer cells still may elicit a cancer progressive phenotype based on effects of TK1, but that a system which isolates TK1 is not effective to understand the effects. Instead, identifying protein networks inclusive of TK1 will help to elucidate its effects on cancer progression.

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Anti-Proliferative and Apoptosis-Inducing Effect of Theabrownin against Non-small Cell Lung Adenocarcinoma A549 Cells

Cited by 32 publications

References 41 publications

Theabrownin triggers DNA damage to suppress human osteosarcoma U2OS cells by activating p53 signalling pathway

Theabrownin triggers DNA damage to suppress human osteosarcoma U2OS cells by activating p53 signalling pathway

Theaflavin Induces Apoptosis of A375 Human Melanoma Cells and Inhibits Tumor Growth in Xenograft Zebrafishes Through P53- and JNK-Related Mechanism

TK1 in Cancer Progression: elucidating its influence on cellular invasion and survival

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