Anti-Colon Cancer Effects of 6-Shogaol Through G2/M Cell Cycle Arrest by p53/p21-cdc2/cdc25A Crosstalk

Qi, Lian‐Wen; Zhang, Zhe; Zhang, Chunfeng; Anderson, Samantha; Li, Qun; Yuan, Chun‐Su; Wang, Chong‐Zhi

doi:10.1142/s0192415x15500469

Cited by 50 publications

(28 citation statements)

References 30 publications

(29 reference statements)

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“…Furthermore, by using HCT-116 and IEC-6 cells, we found that the impact of CELF1 on enterocyte proliferation is highly dependent on p53. Of note, a number of previous studies have revealed that ectopic overexpression of p53 induces G2 arrest in HCT-116 cells (42,43) and induces G1 arrest in IEC-6 cells (44,45). Likewise, our results indicated that ectopic overexpression of CELF1 exhibited the same impact on these cell lines as p53 did, and could be significantly by p53 silencing.…”

Section: Discussionsupporting

confidence: 80%

CELF1/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition

et al. 2018

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Intestinal villus atrophy is a major complication of total parenteral nutrition (TPN). Our previous study revealed that TPN‐induced villus atrophy is accompanied by elevated expression of CUGBP, Elav‐like family member 1 (CELF1); however, its mechanism of action has not been fully understood. Herein, we report a pivotal role of CELF1/p53 axis, which induces a sustained antiproliferative signal, leading to suppressed proliferation of intestinal epithelial cells (IECs). By using a rat model of TPN, we found synchronous upregulation of CELF1 and p53 in jejunum mucosa, accompanied by a 51% decrease in crypt cell proliferation rate. By using HCT‐116 cells as an IEC model in vitro, we found that the expression of CELF1 altered dynamically in parallel to proliferation rate, suggesting a self‐adaptive expression pattern in IECs in vitro. Furthermore, ectopic overexpression of CELF1 elicited a significant antiproliferative effect in HCT‐116, Caco‐2, and IEC‐6 cells, whereas knockdown of CELF1 elicited a significant proproliferative effect. Moreover, cell‐cycle assay revealed that ectopic overexpression of CELF1 induced sustained G2 arrest and G1 arrest in HCT‐116 and IEC‐6 cells, respectively, which could be abolished by p53 silencing. Mechanistically, polysomal profiling and nascent protein analysis revealed that regulation of p53 by CELF1 was mediated through accelerating its protein translation in polysomes. Taken together, our findings revealed a sustained suppression of IEC proliferation evoked by CELF1/p53 axis, which may be a potential therapeutic target for the treatment of TPN‐induced villus atrophy.—Yan, J.‐K., Zhang, T., Dai, L.‐N., Gu, B.‐L., Zhu, J., Yan, W.‐H., Cai, W., Wang, Y. CELF1/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition. FASEB J. 33, 3378–3391 (2019). http://www.fasebj.org

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Section: Discussionsupporting

confidence: 80%

CELF1/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition

et al. 2018

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“…The anti-cancer effect of ginger on patients with colon cancer and other gastrointestinal cancers was emphasized in other studies (39)(40)(41)(42).…”

Section: Discussionmentioning

confidence: 98%

Comparison of the Complications of Platinum-Based Adjuvant Chemotherapy With and Without Ginger in a Pilot Study on Ovarian Cancer Patients

Shokri¹,

Gharebaghi²,

Esfahani³

et al. 2016

International Journal of Women’s Health and Reproduction Scienc

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Introduction Of all the female malignancies, most clinical discussions focus on ovarian cancer. It has the highest case fatality ratio and it is the fifth most common cause of malignancyrelated death among women. The cancer is associated with low parity and infertility. Early menarche and late menopause increase the risk of ovarian cancer. Ovarian cancers include epithelial and non-epithelial tumors. More than 80% of epithelial ovarian cancers are seen in postmenopausal women. The peak incidence of epithelial ovarian cancer is between 55 to 60 years of age. Data show that feature of CA125 increases if the test is performed by transvaginal ultrasound. Its symptoms include complex pelvic mass such as solid pattern, heterogeneous component with irregular thick septum, bilateral masses, and size of lesions exceeding 8 cm. The effective factors in the prognosis of ovarian cancer are divided into the 3 categories of pathological, biological and clinical factors. The pathological factors include the structure and degree of lesion. The biological factors include ploidy and proto-oncogenes such as HER-2neu. The clinical factors include the stage of tumor, the extent of residual disease after primary surgery, volume of ascites, age of the patient, and functional status of patient. Ovarian cancer treatment includes primary cytoreductive and then chemotherapy (1). Chemotherapy may be associated with the complications such as nausea and vomiting, bone marrow depression, peripheral neuropathy, weight loss, hemolytic anemia, and transient cortical blindness (2). Ginger is a plant with anti-carcinogenic and antioxidative effects and modern studies have shown other treatment effects such as the ability to inhibit formation of inflammatory products, direct anti-inflammatory effects, and anti-tumoral effects. It has been proved that the active ingredient in ginger can kill cancer cells due to apoptosis and autophagocytosis. This has also been emphasized in ovarian cancers (2). On the other hand, although chemotherapy drugs suppress inflammatory markers, cancer cells may show resistance to them. It has been proved that ginger can

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“…Proliferation inhibition and apoptosis induction can be trigger by cell cycle arrest in cancer cells ( 26 ). Cdc2 and cyclin B1 are involved in controlling the G2/M checkpoint ( 27 ), and some anticancer-drugs induce G2/M arrest by deregulating the expression of cyclin B1 and Cdc2 ( 28 , 29 ). The results in the present study indicated that treatment of the prostate cancer cells with Scutellarin induced G2/M arrest which was mainly due to a decrease in cyclin B1 and Cdc2 expression.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic and chemosensitization effects of Scutellarin from traditional Chinese herb Scutellaria altissima L. in human prostate cancer cells

et al. 2017

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Scutellaria altissima L. is a common traditional Chinese medicine used to treat inflammation in some countries. Scutellarin, an active major flavone glycoside isolated from the traditional Chinese medicine Scutellaria altissima L., has been shown to offer various beneficial biochemical effects on cerebrovascular diseases and inflammation. However, the antiproliferative effects of Scutellarin in prostate cancer and the underlying mechanism are not fully elucidated. In the present study, we aimed to ascertain whether Scutellarin inhibits cancer cell growth and to further explore the molecular mechanism. Scutellarin enhanced the sensitivity of prostate cancer cells to cisplatin. MTT assays revealed that cell viability was significantly decreased in the prostate cancer cells treated with Scutellarin. Flow cytometric analysis indicated that Scutellarin suppressed cell proliferation by promoting G2/M arrest and inducing apoptosis. We employed western blotting to delineate the underlying mechanisms involved in the G2/M arrest and apoptosis. Comet assay and γH2AX immunocytochemistry were used to detect levels of DNA damage in PC3 cells exposed to Scutellarin and/or cisplatin. Our data revealed that Scutellarin significantly induced prostate cancer cell apoptosis by activating the caspase cascade. An increase in the Bax/Bcl-2 ratio, depolarization of mitochondrial membrane potential and cell cycle arrest at G2/M phase were accompanied by the apoptosis induction. Additionally, Scutellarin altered the protein expression of cell cycle and apoptosis regulatory genes by downregulating Cdc2, cyclin B1 and Bcl-2 and upregulating caspase-3, caspase-9 and Bax in prostate cancer cells. Furthermore, Scutellarin sensitized PC3 cells to cisplastin treatment in a dose-dependent manner. Taken together, our data confirmed the cytotoxicity of Scutellarin against prostate cancer PC3 cells and provide new findings in regards to Scutellarin sensitizing prostate cancer cells to chemotherapy. Our findings suggest that Scutellarin has potential to be used as a novel antineoplastic therapeutic candidate for prostate cancer patients.

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Anti-Colon Cancer Effects of 6-Shogaol Through G2/M Cell Cycle Arrest by p53/p21-cdc2/cdc25A Crosstalk

Cited by 50 publications

References 30 publications

CELF1/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition

CELF1/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition

Comparison of the Complications of Platinum-Based Adjuvant Chemotherapy With and Without Ginger in a Pilot Study on Ovarian Cancer Patients

Cytotoxic and chemosensitization effects of Scutellarin from traditional Chinese herb Scutellaria altissima L. in human prostate cancer cells

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