Shikonin-induced Apoptosis of Colon Cancer Cells Is Reduced by Peroxiredoxin V Expression

Chandimali, Nisansala; Sun, Haiyan; Kong, Ling-Zu; Xing, Zhen; Liu, Ren; Kwon, Taeho; Lee, Dong‐Sun

doi:10.21873/anticanres.13819

Cited by 19 publications

(25 citation statements)

References 29 publications

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“…Shikonin is a small-molecule compound extracted from the natural plant Arnebia euchroma and induces tumor cell apoptosis (23)(24)(25), inhibits DNA topoisomerase (26) and protein tyrosine kinase (26), represses human telomerase activity (27), suppresses tumor angiogenesis (28), alters tumor cell signal transduction and activates mitogen activated protein kinase (MAPK) through chemical protection and induces antimitotic effects (29). Furthermore, shikonin inf luences the metabolism, proliferation, differentiation, signal transmission, gene expression, cell growth, invasion and metastasis of tumor cells (30-32).…”

Section: Discussionmentioning

confidence: 99%

The compound 2‑benzylthio‑5,8‑dimethoxynaphthalene‑1,4‑dione leads to apoptotic cell death by increasing the cellular reactive oxygen species levels in Ras‑mutated liver cancer cells

Shen

Sun

et al. 2020

Exp Ther Med

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The aim of the present study was to verify the pro-apoptotic anticancer potential of several 5,8-dimethoxy-1,4-phthoquinone (DMNQ) derivatives in Ras-mediated tumorigenesis. MTT assays were used to detect cellular viability and flow cytometry was performed to assess intracellular reactive oxygen species (ROS) levels and apoptosis. The expression levels of proteins were detected via western blotting. Among the 12 newly synthesized DMNQ derivatives, 2-benzylthio-5,8-dimethoxynaphthalene-1,4-dione (BZNQ; component #1) significantly reduced cell viability both in mouse NIH3T3 embryonic fibroblasts cells (NC) and H-Ras G12V transfected mouse NIH3T3 embryonic fibroblasts cells (NR). Moreover, BZNQ resulted in increased cytotoxic sensitivity in Ras-mutant transfected cells. Furthermore, the reactive oxygen species (ROS) levels in H-Ras G12V transfected HepG2 liver cancer cells (HR) were significantly higher compared with the levels in HepG2 liver cancer cells (HC) following BZNQ treatment, which further resulted in increased cellular apoptosis. Eliminating cellular ROS using an ROS scavenger N-acetyl-L-cysteine markedly reversed BZNQ-induced cellular ROS accumulation and cell apoptosis in HC and HR cells. Western blotting results revealed that BZNQ significantly downregulated H-Ras protein expression and inhibited the Ras-mediated downstream signaling pathways such as protein kinase B, extracellular signal-related kinase and glycogen synthase kinase phosphorylation and β-catenin protein expression. These results indicated that the novel DMNQ derivative BZNQ may be a therapeutic drug for Ras-mediated liver tumorigenesis. The results of the current study suggest that BZNQ exerts its effect by downregulating H-Ras protein expression and Ras-mediated signaling pathways.

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Section: Discussionmentioning

confidence: 99%

The compound 2‑benzylthio‑5,8‑dimethoxynaphthalene‑1,4‑dione leads to apoptotic cell death by increasing the cellular reactive oxygen species levels in Ras‑mutated liver cancer cells

Shen

Sun

et al. 2020

Exp Ther Med

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“…Nuclei were stained for 15 min with 2-(4-amidinophenyl)-1H-indole-6-carboxamidine. Images were captured under an inverted microscope (14).…”

Section: -(45-dimethylthiazol-2-yl)-25-diphenyltetrazolium Bromidementioning

confidence: 99%

“…CD133 + Cal72 cells were seeded in 6-well plates in growth medium and treated with wogonin (0, 20, 40, 80 μM) with or without 5 mM NAC. After 24 h, cells were incubated with 20 μM DCF-DA in a dish at 37˚C for 20 min then fluorescence imaging and flow cytometry (BD Biosciences, San Jose, CA, USA) were performed (10,14).…”

Section: Ros Detection With 2'7'-dichlorofluorescin Diacetate (Dcf-da)mentioning

confidence: 99%

“…CD133 + Cal72 cells were seeded at 2×10 3 cells/well in 6-well Ultra Low Cluster plates (Corning, New York City, NY, USA). The cells were cultured with DMEM/F12 (Invitrogen) containing 2% B27 supplement (Invitrogen), 10 ng/ml hEGF, 20 ng/ml basic fibroblast growth factor (bFGF), and 1% antibiotics, and treated with wogonin (0, 20, 40, 80 μM) with or without 5 mM NAC for 7 days (10,14). The size of spheres was estimated under a microscope.…”

Section: Ros Detection With 2'7'-dichlorofluorescin Diacetate (Dcf-da)mentioning

confidence: 99%

“…CD133 + Cal72 cells were seeded at 5×10 4 cells/well in 96-well and allowed to grow to 98-100% confluence. Using a wound maker (Essen Bioscience, Ann Arbor, MI, USA), a linear scratch was made in the cell layer (10,14). Cells were washed with 1X phosphate-buffered saline and DMEM containing wogonin (0, 20, 40, 80 μM) and 0.5% FBS was added.…”

Section: Ros Detection With 2'7'-dichlorofluorescin Diacetate (Dcf-da)mentioning

confidence: 99%

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Wogonin Influences Osteosarcoma Stem Cell Stemness Through ROS-dependent Signaling

Koh

Sun

Xing

et al. 2020

In Vivo

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Backgorund/Aim: Wogonin, a flavonoid-like compound extracted from the root of Scutellaria baicalensis Georgi, has been shown to have anticancer effects against cancer cells. Osteosarcoma is the most malignant type of bone cancer and can appear in any bone, with a high propensity for relapse and metastasis. The present study aimed to assess the anticancer effects of wogonin on osteosarcoma stem cells. Materials and Methods: The cytotoxic effects of wogonin on CD133 + Cal72 osteosarcoma stem cells were assessed through in vitro experiments by MTT assay, transwell assay, sphere-formation assay, flow cytometry, immunocytochemistry and western blotting. Results: Wogonin suppressed stem cell characteristics and the expression of stem cell-related genes by regulating reactive oxygen species (ROS) levels and ROS-related signaling of CD133 + Cal72 cells, effects which were reversed by ROS scavenger N-acetylcysteine. Conclusion: Wogonin may be a promising candidate for successful clinical management of osteosarcoma by regulating ROSrelated mechanisms and stem cell-related genes. Osteosarcoma, the most common type of malignant bone tumor, is most prevalent among children and adolescents and accounts for 2.4% of pediatric cancer cases (1). It is most common among the ages of 10-16 years and the second most common among those aged over 40 years. The tumor is potentially present in bone marrow and then may grow into a mass of tumors and can occur in any bone (2). At present, the first-line treatment for most osteosarcoma involves surgery with intensive adjuvant chemotherapy (3). However, many patients still have poor survival due to relapse and metastasis of osteosarcoma (4). Cancer stem cells (CSCs) are cancer cells that have characteristics related to stem cells, such as self-renewal and differentiation abilities (5). Expression of CSC genes is known to induce cancer metastasis (6). In particular, it was reported that osteosarcoma stem cells have a high capacity for tumor metastasis (2). A pentaspan membrane glycoprotein, CD133, is one of the most well-known biomarkers used for the detection of CSCs. It plays an important role in tumor growth, metastasis, tumorigenesis and tumor relapse (7). Finding a drug candidate involved in down-regulating the expression of genes related to osteosarcoma stem cell behaviour is an urgent need. Reactive oxygen species (ROS) are forms of active oxygen and result from cellular metabolism (8). Some studies have revealed that an increased ROS level reduces the expression of stemness-related genes in CSCs and this effect can be reversed by ROS scavengers such as Nacetylcysteine (NAC) (9, 10). Wogonin (5,7-dihydroxy-8-methoxyflavone) is a flavonoid-like compound that extracted from the root of Scutellaria baicalensis Georgi (Figure 1A) (11). It is wellknown for diverse biological effects such as anti-1077 This article is freely accessible online.

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Epigallocatechin gallate triggers apoptosis by suppressing de novo lipogenesis in colorectal carcinoma cells

et al. 2022

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The de novo lipogenesis (DNL) pathway has been identified as a regulator of cancer progression and aggressiveness. Downregulation of key lipogenesis enzymes has been shown to activate apoptosis in cancerous cells. Epigallocatechin gallate (EGCG) inhibits cancer cell proliferation without causing cytotoxicity in healthy cells. The present study aimed to investigate the effects of EGCG on the promotion of apoptosis associated with the DNL pathway inhibition in cancer cells, both in vitro and in vivo. We observed that two colorectal cancer cell lines (HCT116 and HT‐29) had a higher cytotoxic response to EGCG treatment than hepatocellular carcinoma cells, including HepG2 and HuH‐7. EGCG treatment decreased cell viability and increased mitochondrial damage‐triggered apoptosis in both HCT116 and HT‐29 cancer cells. Additionally, we treated mice transplanted with HCT116 cells with 30 or 50 mg·kg−1 EGCG for 7 days to evaluate the apoptotic effects of EGCG treatment in a xenograft mouse model of cancer. We observed a decrease in intracellular fatty acid levels, which suggested that EGCG‐induced apoptosis was associated with a decrease in fatty acid levels in cancer. Suppression of ATP synthesis by EGCG indicated that cell death induction in cancer cells could be mediated by shared components of the DNL and energy metabolism pathways. In addition, EGCG‐induced apoptosis suppressed the expression of the phosphorylation protein kinase B and extracellular signal‐regulated kinase 1/2 signaling proteins in tumors from xenografted mice. Cytotoxic effects in unaffected organs and tissues of the mouse xenograft model were absent upon EGCG treatment.

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Shikonin-induced Apoptosis of Colon Cancer Cells Is Reduced by Peroxiredoxin V Expression

Cited by 19 publications

References 29 publications

The compound 2‑benzylthio‑5,8‑dimethoxynaphthalene‑1,4‑dione leads to apoptotic cell death by increasing the cellular reactive oxygen species levels in Ras‑mutated liver cancer cells

The compound 2‑benzylthio‑5,8‑dimethoxynaphthalene‑1,4‑dione leads to apoptotic cell death by increasing the cellular reactive oxygen species levels in Ras‑mutated liver cancer cells

Wogonin Influences Osteosarcoma Stem Cell Stemness Through ROS-dependent Signaling

Epigallocatechin gallate triggers apoptosis by suppressing de novo lipogenesis in colorectal carcinoma cells

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