Esculetin induces death of human colon cancer cells via the reactive oxygen species-mediated mitochondrial apoptosis pathway

Kim, Areum Daseul; Han, Xiaodong; Piao, Mei Jing; Hewage, Susara Ruwan Kumara Madduma; Hyun, Chang Lim; Cho, Suk Ju; Hyun, Jin Won

doi:10.1016/j.etap.2015.03.003

Cited by 46 publications

(39 citation statements)

References 28 publications

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“…Recently, we reported that esculetin reduces the viability of HT‐29 cells in a dose‐dependent manner and that the concentration of esculetin that yielded 50% growth inhibition (IC 50 ) was 55 µg ml −1 . Therefore, this dose was used for all experiments reported herein.…”

Section: Resultsmentioning

confidence: 99%

“…It has also been proven for cancer chemopreventive and anti‐tumour activities . Recently, we showed that esculetin induces apoptosis by reducing BCL2 levels, up‐regulating BCL2‐associated X protein (BAX) and disrupting the mitochondrial membrane potential in human colon cancer cells, leading to the activation of caspase‐9 and caspase‐3 . However, little is known about the involvement of ER stress in this process.…”

Section: Introductionmentioning

confidence: 99%

“…19 Recently, we showed that esculetin induces apoptosis by reducing BCL2 levels, up-regulating BCL2-associated X protein (BAX) and disrupting the mitochondrial membrane potential in human colon cancer cells, leading to the activation of caspase-9 and caspase-3. 20 However, little is known about the involvement of ER stress in this process. To address this issue, we investigated whether esculetin-induced apoptosis of human colon cancer cells is mediated via ER stress.…”

Section: Introductionmentioning

confidence: 99%

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Esculetin induces apoptosis in human colon cancer cells by inducing endoplasmic reticulum stress

Kim

Hewage

Piao

et al. 2015

Cell Biochemistry & Function

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Colorectal cancer has become more common in many regions of the world. Recently, we showed that esculetin, a natural coumarin, induces apoptosis in HT-29 colon cancer cells via the reactive oxygen species-mediated mitochondrial pathway. The present study examined whether esculetin induces apoptosis in HT-29 colon cancer cells by inducing endoplasmic reticulum (ER) stress. We found that esculetin induced characteristic signs of ER stress, confirmed by ER staining, mitochondrial calcium overload and expression of ER stress-related proteins (i.e. glucose regulated protein 78, phosphorylated ribonucleic acid-dependent protein kinase-like ER kinase, phosphorylated inositol requiring enzyme 1, phosphorylated eukaryotic initiation factor-2α, spliced X-box binding protein 1 and cleaved activating transcription factor 6). Esculetin also induced the expression of the CCAAT/enhancer-binding protein-homologous protein (CHOP) and pro-apoptotic factors caspase-12. Moreover, transfection of colon cancer cells with a small interfering ribonucleic acid targeting CHOP attenuated esculetin-induced apoptosis. Taken together, these results suggest that the ER stress response plays an important role in esculetin-induced apoptosis in human colon cancer cells.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Esculetin induces apoptosis in human colon cancer cells by inducing endoplasmic reticulum stress

Kim

Hewage

Piao

et al. 2015

Cell Biochemistry & Function

Self Cite

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“…The translocation of Bcl-2 proteins cause cytochrome c release into the cytoplasm, where it unites with Apaf-1 leading to activation of procaspase-9 by proteolytic cleavage. Activated caspase-9 in turn cleaves and activates procaspase-3 [28,55].…”

Section: Discussionmentioning

confidence: 99%

Turkish propolis supresses MCF-7 cell death induced by homocysteine

Tartik

Darendelioğlu

Aykutoğlu

et al. 2016

Biomedicine & Pharmacotherapy

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“…ESC is found in many medicinal plants, such as Artemisia capillaries , Citrus limonia , and Euphorbia lathyris . ESC has been reported to exhibit a wide range of biological and pharmacological properties including anti‐inflammatory, anti‐oxidant, anti‐edema, and anti‐tumor promoting properties . In addition, many previous studies have reported that ESC induces apoptosis in various cancer cells such as oral cancer, skin cancer, lung cancer, and gastric cancer .…”

Section: Introductionmentioning

confidence: 99%

Esculetin induces cell cycle arrest and apoptosis in human colon cancer LoVo cells

Choi

Lee

Park

et al. 2019

Environmental Toxicology

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We investigated the anti‐cancer effects of ESC in human colon cancer LoVo cells. Cell counting assay results showed that ESC inhibited the proliferation of LoVo cells. Cell cycle arrest results showed that cell cycle was arrested during the G0/G1 phase in the ESC‐treated LoVo cells. Western blot results showed that the cell cycle inhibitory proteins p53, p27, and p21 were increased, and cyclin D1, the cell cycle progressive protein, was decreased. Sp1 is a transcription factor regulating cell proliferation, was decreased in the ESC‐treated LoVo cells. Annexin V/propidium iodide staining results showed that ESC induces apoptosis in LoVo cells. Western blot results showed that Bax, cleaved caspase ‐3, ‐7, ‐9, and poly(ADP‐ribose) polymerase, which are proapoptotic proteins, were increased and the antiapoptotic protein Bcl‐2 was decreased. Taken together, ESC induced apoptosis and has an anti‐cancer effect in LoVo cells.

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Esculetin induces death of human colon cancer cells via the reactive oxygen species-mediated mitochondrial apoptosis pathway

Cited by 46 publications

References 28 publications

Esculetin induces apoptosis in human colon cancer cells by inducing endoplasmic reticulum stress

Esculetin induces apoptosis in human colon cancer cells by inducing endoplasmic reticulum stress

Turkish propolis supresses MCF-7 cell death induced by homocysteine

Esculetin induces cell cycle arrest and apoptosis in human colon cancer LoVo cells

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