Eupatilin Impacts on the Progression of Colon Cancer by Mitochondria Dysfunction and Oxidative Stress

Lee, Minkyeong; Yang, Changwon; Song, Gwonhwa; Lim, Whasun

doi:10.3390/antiox10060957

Cited by 11 publications

(7 citation statements)

References 46 publications

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“…HCT116 and HT-29 cells were acquired from the Korean Cell Line Bank, and the former were cultured for at least 6 months to obtain cells resistant to 5-FU (5-FU-R), by adding progressively increasing 5-FU concentrations starting at 0.5 μM. In our prior experiment, the half-maximal inhibitory concentration (IC 50 ) of cell viability to 5-FU of 5-FU-R HCT116 cells was 16.1 μM, whereas, in parental HCT116 cells, it was 1.9 μM [ 15 ]. Experiments with 5-FU-R cells were conducted in triplicate.…”

Section: Methodsmentioning

confidence: 99%

Polydatin Counteracts 5-Fluorouracil Resistance by Enhancing Apoptosis via Calcium Influx in Colon Cancer

et al. 2021

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Colon cancer is a disease with a high prevalence rate worldwide, and for its treatment, a 5-fluorouracil (5-FU)-based chemotherapeutic strategy is generally used. However, conventional anticancer agents have some limitations, including the development of drug resistance. Therefore, there has recently been a demand for the improvement of antitumor agents using natural products with low side effects and high efficacy. Polydatin is a natural active compound extracted from an annual plant, and widely known for its anticancer effects in diverse types of cancer. However, it is still not clearly understood how polydatin ameliorates several drawbacks of standard anticancer drugs by reinforcing the chemosensitivity against 5-FU, and neither are the intrinsic mechanisms behind this process. In this study, we examined how polydatin produces anticancer effects in two types of colon cancer, called HCT116 and HT-29 cells. Polydatin has the ability to repress the progression of colon cancer, and causes a modification of distribution in the cell cycle by a flow cytometry analysis. It also induces mitochondrial dysfunctions through oxidative stress and the loss of mitochondrial membrane potential. The present study investigated the apoptosis caused by the disturbance of calcium regulation and the expression levels of related proteins through flow cytometry and immunoblotting analysis. It was revealed that polydatin suppresses the signaling pathways of the mitogen-activated protein kinase (MAPK) and PI3K/AKT. In addition, it was shown that polydatin combined with 5-FU counteracts drug resistance in 5-FU-resistant cells. Therefore, this study suggests that polydatin has the potential to be developed as an innovative medicinal drug for the treatment of colon cancer.

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Section: Methodsmentioning

confidence: 99%

Polydatin Counteracts 5-Fluorouracil Resistance by Enhancing Apoptosis via Calcium Influx in Colon Cancer

et al. 2021

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“…Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is a flavone derived from the plant genus Artemisia with different anti-oxidant (36,37), anti-ulcerative (38), anti-cancer (39,40) and antiinflammatory (41,42) properties (43). Eupatilin is prescribed clinically in South Korea for the treatment of gastritis and peptic ulcers under the name of Stillen TM (44).…”

Section: Discussionmentioning

confidence: 99%

Eupatilin improves cilia defects in human CEP290 ciliopathy models

Corral-Serrano¹,

Sladen²,

Ottaviani

et al. 2023

Preprint

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The photoreceptor outer segment is a highly specialized primary cilium essential for phototransduction and vision. Biallelic pathogenic variants in the cilia-associated gene CEP290 cause non-syndromic Leber congenital amaurosis 10 (LCA10) and syndromic diseases, where the retina is also affected. While RNA antisense oligonucleotides and gene editing are potential treatment options for the common deep intronic variant c.2991+1655A>G in CEP290, there is a need for variant-independent approaches that could be applied to a broader spectrum of ciliopathies. Here, we generated several distinct human models of CEP290-related retinal disease and investigated the effects of the flavonoid eupatilin as a potential treatment. Eupatilin improved cilium formation and length in CEP290 LCA10 patient-derived fibroblasts, in gene-edited CEP290 knockout (CEP290 KO) RPE1 cells, and in both CEP290 LCA10 and CEP290 KO iPSCs-derived retinal organoids. Furthermore, eupatilin reduced rhodopsin retention in the outer nuclear layer of CEP290 LCA10 retinal organoids. Eupatilin altered gene transcription in retinal organoids, by modulating the expression of rhodopsin, and by targeting cilia and synaptic plasticity pathways. This work sheds light into the mechanism of action of eupatilin, and supports its potential as a variant-independent approach for CEP290-associated ciliopathies.

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“…The induction of oxidative stress, representative of ROS generation, is a promising therapeutic strategy to promote cancer cell death. Cancer cells can be specifically targeted by taking advantage of the fact that ROS levels remain high in cancer cells, compared with that of normal cells, and inducing excessive intracellular ROS [ 30 , 31 , 32 , 33 ]. Quercetin was found to induce high levels of intracellular and mitochondrial-specific ROS in CRC cells, and this increase was independent of the status of p53.…”

Section: Discussionmentioning

confidence: 99%

Targeting Thymidylate Synthase and tRNA-Derived Non-Coding RNAs Improves Therapeutic Sensitivity in Colorectal Cancer

et al. 2022

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Some colorectal cancer (CRC) patients are resistant to 5-fluorouracil (5-FU), and high expression levels of thymidylate synthase (TS) contribute to this resistance. This study investigated whether quercetin, a representative polyphenol compound, could enhance the effect of 5-FU in CRC cells. Quercetin suppressed TS levels that were increased by 5-FU in CRC cells and promoted the expression of p53. Quercetin also induced intracellular and mitochondrial reactive oxygen species (ROS) production and Ca2+ dysregulation in a 5-FU-independent pathway in CRC cells. Furthermore, quercetin decreased mitochondrial membrane potential in CRC cells and inhibited mitochondrial respiration. Moreover, quercetin regulated the expression of specific tiRNAs, including tiRNAHisGTG, and transfection of a tiRNAHisGTG mimic further enhanced the apoptotic effect of quercetin in CRC cells. An enhanced sensitivity to 5-FU was also confirmed in colitis-associated CRC mice treated with quercetin. The treatment of quercetin decreased survival rates of the CRC mouse model, with reductions in the number of tumors and in the disease activity index. Also, quercetin suppressed TS and PCNA protein expression in the distal colon tissue of CRC mice. These results suggest that quercetin has the potential to be used as an adjuvant with 5-FU for the treatment of CRC.

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Eupatilin Impacts on the Progression of Colon Cancer by Mitochondria Dysfunction and Oxidative Stress

Cited by 11 publications

References 46 publications

Polydatin Counteracts 5-Fluorouracil Resistance by Enhancing Apoptosis via Calcium Influx in Colon Cancer

Polydatin Counteracts 5-Fluorouracil Resistance by Enhancing Apoptosis via Calcium Influx in Colon Cancer

Eupatilin improves cilia defects in human CEP290 ciliopathy models

Targeting Thymidylate Synthase and tRNA-Derived Non-Coding RNAs Improves Therapeutic Sensitivity in Colorectal Cancer

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