Anti-cancer effects of the aqueous extract of Orostachys japonica A. Berger on 5-fluorouracil-resistant colorectal cancer via MAPK signalling pathways in vitro and in vivo

Kim, Jung Ho; Kim, Sang Hee; Mariappan, Ramesh; Moon, Daeun; Kim, Jinu

doi:10.1016/j.jep.2021.114412

Cited by 6 publications

(6 citation statements)

References 45 publications

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“…SNU-C5 (IC 50 against 5-FU = 5 µM) cell line was purchased from the Korean Cell Line Bank (Seoul, Republic of Korea), and 5-FU-resistant SNU-C5 (SNU-C5/ 5-FUR; IC 50 against 5-FU = 140 µM) cell line was obtained from the Research Center for Resistant Cells (Chosun University, Gwangju, Republic of Korea). Cells were cultured in RPMI-1640 medium (Welgene, Gyeongsan, Republic of Korea) supplemented with 10 % fetal bovine serum (FBS) and 1 % penicillin-streptomycin at 37 ºC in a 5 % CO 2 incubator as previously described (Moon et al, 2020;Kim et al, 2021).…”

Section: Methodsmentioning

confidence: 99%

Protective Autophagy in 5-Fluorouracil-Resistant Colorectal Cancer Cells and ERK-RSK-ABCG2 Linkage

Yoon

2023

Int. J. Morphol.

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To evaluate the anti-cancer effects of yeast extract on resistant cells, autophagy and necroptosis were investigated in 5-fluorouracil (5-FU)-resistant colorectal cancer cells. Further underlying characteristics on drug resistance were evaluated, focused on ERK-RSK-ABCG2 linkage. SNU-C5 and 5-FU resistant SNU-C5 (SNU-C5/5-FUR) colorectal cancer cells were adopted for cell viability assay and Western blotting to examine the anti-cancer effects of yeast extract. Yeast extract induced autophagy in SNU-C5 cells with increased Atg7, Atg12-5 complex, Atg16L1, and LC3 activation (LC3-II/LC3-I), but little effects in SNU-C5/5-FUR cells with increased Atg12-5 complex and Atg16L1. Both colorectal cancer cells did not show necroptosis after yeast extract treatment. Based on increased ABCG2 and RSK expression after yeast extract treatment, drug resistance mechanisms were further evaluated. As compared to wild type, SNU-C5/5-FUR cells showed more ABCG2 expression, less RSK expression, and less phosphorylation of ERK. ABCG2 inhibitor, Ko143, treatment induces following changes: 1) more sensitivity at 500 mM 5-FU, 2) augmented proliferation, and 3) less phosphorylation of ERK. These results suggest that protective autophagy in SNU-C5/5-FUR cells with increased ABCG2 expression might be candidate mechanisms for drug resistance. As the ERK responses were different from each stimulus, the feasible mechanisms among ERK-RSK-ABCG2 should be further investigated in 5-FU-resistant CRC cells.

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Section: Methodsmentioning

confidence: 99%

Protective Autophagy in 5-Fluorouracil-Resistant Colorectal Cancer Cells and ERK-RSK-ABCG2 Linkage

Yoon

2023

Int. J. Morphol.

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“…SNU-C5 (IC 50 against 5-FU = 5 μM) and the 5-fluorouracil-resistant SNU-C5 (SNU-C5/5-FUR; IC 50 against 5-FU = 140 μM) cell lines were cultured as previously described [ 19 , 32 ].…”

Section: Methodsmentioning

confidence: 99%

“…Cells were treated with or without fenbendazole (0.5 and 5.0 μM for SNU-C5 and SNU-C5/5-FUR cells, respectively) for 3 days, followed by flow cytometry using the FACSCalibur system (BD Biosciences, San Jose, CA, USA) and BD FACStation software version 6.0 (BD Biosciences) as described previously [ 19 , 32 ].…”

Section: Methodsmentioning

confidence: 99%

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Anti-cancer effects of fenbendazole on 5-fluorouracil-resistant colorectal cancer cells

Park

Lee

Yoon

2022

Korean J Physiol Pharmacol

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Benzimidazole anthelmintic agents have been recently repurposed to overcome cancers resistant to conventional therapies. To evaluate the anti-cancer effects of benzimidazole on resistant cells, various cell death pathways were investigated in 5-fluorouracil-resistant colorectal cancer cells. The viability of wild-type and 5-fluorouracil-resistant SNU-C5 colorectal cancer cells was assayed, followed by Western blotting. Flow cytometry assays for cell death and cell cycle was also performed to analyze the anti-cancer effects of benzimidazole. When compared with albendazole, fenbendazole showed higher susceptibility to 5-fluorouracil-resistant SNU-C5 cells and was used in subsequent experiments. Flow cytometry revealed that fenbendazole significantly induces apoptosis as well as cell cycle arrest at G2/M phase on both cells. When compared with wild-type SNU-C5 cells, 5-fluorouracil-resistant SNU-C5 cells showed reduced autophagy, increased ferroptosis and ferroptosis-augmented apoptosis, and less activation of caspase-8 and p53. These results suggest that fenbendazole may be a potential alternative treatment in 5-fluorouracil-resistant cancer cells, and the anticancer activity of fenbendazole does not require p53 in 5-fluorouracil-resistant SNU-C5 cells.

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“…The differential activation of extracellular signal-regulated protein kinase (ERK) between wild type and 5-FU-resistant CRC cells after yeast extract treatment has been previously suggested by the authors ( 8 ). It has also been reported that SNU-C5/5-FUR cells are more susceptible to an aqueous extract of Orostachys japonica A. Berger than wild type SNU-C5 cells via the activation of mitogen-activated protein kinase signaling pathways including ERK and p38 ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Increased soluble E‑cadherin of spheroid formation supplemented with fetal bovine serum in colorectal cancer cells

Chang

Yoon

2023

Oncol Lett

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Cancer stem cells (CSCs) are known to be a major cause of metastasis, resistance and recurrence. Spheroid formation is one of the methods used to recruit CSCs utilizing an anchorage-independent environment in vitro. It was aimed to investigate the availability of spheroid formation culture methods in the research field of CSCs and resistance using 5-fluorouracil (5-FU)-resistant colorectal cancer cells. The wild type SNU-C5 and 5-FU-resistant SNU-C5 (SNU-C5/5-FUR) cells were cultured as usual (monolayer), and in 3-dimensional non-adhesive environments supplemented with fetal bovine serum (FBS) or growth factors, respectively. The characteristics of the spheroids were evaluated by morphometry, cell viability assay, western blotting, immunocytochemistry and enzyme-linked immunosorbent assay. Spheroid formation was induced in an environment supplemented with FBS, while SNU-C5/5-FUR cells only formed spheres in media supplemented with GFs. Sphere-formed cells showed slower cell proliferation than cells from monolayer, which coincided with an increased level of p21 and a decreased level of β-catenin. Markers for CSCs and drug resistance were not significantly changed after spheroid formation. Sphere-formed cells showed significantly increased levels of soluble E-cadherin, particularly in the environment supplemented with FBS. These results suggested that spheroid formation may be related to soluble E-cadherin, but is not related to CSCs or resistance markers.

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Anti-cancer effects of the aqueous extract of Orostachys japonica A. Berger on 5-fluorouracil-resistant colorectal cancer via MAPK signalling pathways in vitro and in vivo

Cited by 6 publications

References 45 publications

Protective Autophagy in 5-Fluorouracil-Resistant Colorectal Cancer Cells and ERK-RSK-ABCG2 Linkage

Protective Autophagy in 5-Fluorouracil-Resistant Colorectal Cancer Cells and ERK-RSK-ABCG2 Linkage

Anti-cancer effects of fenbendazole on 5-fluorouracil-resistant colorectal cancer cells

Increased soluble E‑cadherin of spheroid formation supplemented with fetal bovine serum in colorectal cancer cells

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