Tunicamycin inhibits colon carcinoma growth and aggressiveness via modulation of the ERK-JNK-mediated AKT/mTOR signaling pathway

Shang, You; Li, Weihong; Guan, Yun

doi:10.3892/mmr.2018.8444

Cited by 18 publications

(17 citation statements)

References 41 publications

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“…The animals were housed in laminar airflow cabinets under pathogen-free conditions with a 12-h light/dark cycle, and were fed autoclaved standard food and water ad libitum . The animal experiment protocol was approved by Peking University Animals Research Committee (Beijing, China) and was conducted in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals ( 10 ). Human MDA-MB-231 cells (4×10 6 ) were diluted in 0.1 ml RPMI-1640 medium, mixed at a 1:1 ratio with Matrigel (BD Biosciences, Franklin Lakes, NJ, USA) to make the percentage of Matrigel 50%.…”

Section: Methodsmentioning

confidence: 99%

Antitumor effects of Xi Huang pills on MDA‑MB‑231 cells in�vitro and in�vivo

et al. 2018

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The management of patients with triple-negative breast cancer is challenging due to the lack of effective therapeutic options, aggressive behavior and relatively poor prognosis. Xi Huang pills (XHP) are a well-known traditional Chinese medicine that demonstrate anticancer activities. The aim of the present study was to investigate the antitumor effects of XHP on MDA-MB-231 cells in vitro and in vivo, and its potential underlying molecular mechanisms. In the present study, an MTT assay was used to evaluate the antiproliferative activity of XHP on MDA-MB-231 cells. In order to investigate the effects further, cell cycle distribution, apoptosis and mitochondrial membrane potential assays were performed, as well as western blot analyses. In addition, a tumor xenograft model was employed to investigate the effects of XHP in vivo. The results of the MTT assay demonstrated that the viability of MDA-MB-231 cells was markedly inhibited by XHP in a dose- and time-dependent manner. The inhibitory effect of XHP on the viability of MDA-MB-231 cells was greater when compared with MCF-10A cells. An increase in apoptosis and loss of mitochondrial membrane potential was observed following 4, 8 and 12 mg/ml XHP treatment of MDA-MB-231 cells. The protein expression levels of cleaved caspase-3 were increased by 1.62-, 2.13- and 2.19-fold, respectively, when compared with the untreated controls, whereas no effects on the expression of B-cell lymphoma 2 (Bcl-2) or Bcl-2-associated X protein (Bax) were observed. The results of the cell cycle distribution assay analysis demonstrated that XHP treatment arrested cells at the G2/M phase. In addition, XHP treatment decreased the expression of cyclin A and increased the expression of p21Cip1. In vivo experiments revealed that XHP inhibited the growth of MDA-MB-231 xenograft tumors without body weight loss, and demonstrated similar effects on the protein expression levels of cleaved caspase 3, cyclin A and p21Cip1 as observed in vitro. In conclusion, the viability of MDA-MB-231 cells was inhibited by XHP in a dose-dependent, time-dependent and cell-selective manner in vitro, and the potential underlying mechanisms may involve apoptosis and cell cycle arrest at the G2/M phase. XHP may induce apoptosis in MDA-MB-231 cells via the intrinsic pathway, which does not involve the Bcl-2/Bax ratio. G2/M phase arrest may have been due to the integrated action of decreased cyclin A expression and increased p21Cip1 expression. In addition, XHP inhibited the growth of xenograft tumors in the absence of body weight loss in vivo.

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Section: Methodsmentioning

confidence: 99%

Antitumor effects of Xi Huang pills on MDA‑MB‑231 cells in�vitro and in�vivo

et al. 2018

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“…Its incidence is high in western countries as well as Iran ranked third among men and fourth in women [14,30]. Surgery, chemotherapy, and radiation therapy are among the main therapeutic modalities for the treatment of colon cancer, however, such treatments are frequently prohibited due to their numerous adverse side effects [3,6]. In most cases the majority of cancer cells might develop resistance to conventional therapeutic agents [4], therefore, targeting vital signaling pathways in colon cancer including those involved in growth signaling cascades, invasion, angiogenesis, and apoptosis is a prompt need which may exert selective cytotoxicity towards cancer cells [1].…”

Section: Discussionmentioning

confidence: 99%

“…Colon cancer, as a complex and multifactorial disease, is one of the most frequent gastrointestinal tract (GIT) malignancies [1] (the second most common cancer in women/ third in men) [2,3], and has the highest cancer-related death among patients affected [4,5], Various factors are involved in its incidence, although its onset is often without any obvious clinical manifestations [6], hence, these patients are detected at advanced stages [1]. The accumulation of mutations in oncogenes and tumor suppressor genes, as well as, lifestyle, dietary factors (high fat, low carbohydrate, red meat consumption, less fruit, and vegetable consumption and alcoholic beverages), environment and carcinogenic chemicals are among factors involved in colon cancer incidence [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…Surgery, chemotherapy, and radiotherapy are among conventional methods for colon cancer treatment [1,4,5,8], which in most cases have low success rates due to adverse side effects [8] and metastasis of chemotherapy-resistant cells [9]. Therefore, there is an urgent need for the development of novel and safe anti-cancer agents [5] based on mechanisms underlying colon cancer cell growth, metastasis and invasion [3].…”

Section: Introductionmentioning

confidence: 99%

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Prophylactic role of Lactobacillus Paracasei exopolysaccharides on colon cancer cells through apoptosis not ferroptosis

Saadat

Gargari

Shahabi

et al. 2020

Preprint

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Nowadays despite conventional methods in colon cancer treatment, targeting vital molecular pathways and induction of various forms of cell death by safe probiotic components like exopolysaccharides (EPSs) are of great importance and are considered as potential therapeutic agents. This study aimed to investigate the inhibitory effect of the EPS of L. paracasei on different colon cancer cell lines (SW-480, HT-29, and HCT-116). For this purpose, several cellular and molecular experiments including MTS assay, DAPI staining, Annexin V/PI assay, quantitative real-time PCR (qPCR) and some important ferroptosis-related assays were performed. Based on the findings, L. paracasei EPS can induce apoptosis confirmed by all apoptosis-related assays and could not act through ferroptosis pathways. L. paracasei EPS could hinder the Akt1, mTOR, and Jak-1 mRNAs, and induces apoptosis through down-regulation of the anti-apoptotic gene (Bcl-2), up-regulation of pro-apoptotic genes (BAX, caspase-3, 8). The exploited EPS of an indigenous probiotic strain with anticancer potential with low/insignificant cytotoxicity to normal cells is proposed for future applications in molecular-targeted therapy of colon cancer treatment. Furthermore, in vivo and clinical trials should be performed to evaluate the applicability of this component besides conventional methods to increase the survival rate of colon cancer patients.

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“…In CRC, tandutinib was reported to inhibit colon cancer growth by suppressing Akt/mTOR signaling pathway [7]. Tunicamycin was found to inhibit the growth and aggressiveness of colon cancer cells through down regulation mTOR expression [8]. Inositol-6 phosphate induces autophagy of HT29 colon cancer cells by inhibiting the Akt/mTOR pathway [9].…”

Section: Introductionmentioning

confidence: 99%

Natural compound rhein suppresses colorectal cancer cells growth through mTOR/p70S6 kinase pathway in vitro and in vivo

Zhang¹,

Park²,

Huang³

et al. 2020

Preprint

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Background: Rhein is a natural agent isolated from the traditional Chinese medicine rhubarb, which has been used as a medicine in China since ancient times. Although rhein was found to have significant anticancer effects in different cancer models, the effect and the underlying mechanisms of action of rhein in colorectal cancer (CRC) remain unclear. The mTOR/p70S6 kinase (p70S6K) pathway has been demonstrated as an attractive target for developing novel cancer therapeutics.Methods: The human CRC cell lines HCT116, HCT15, and DLD1 and xenograft mice were used in this study to investigate the effects of rhein. Assessments of cellular morphology, cell proliferation, and anchorage-independent colony formation were performed to examine the effects of rhein on cell growth. Wound healing assay and transwell migration and invasion assay were conducted to detect cell migration and invasion. Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. Tissue microarray was used to detect mTOR expression in patients with CRC. Gene overexpression and knockdown were implemented to analyze the function of mTOR in CRC. The in vivo effect of rhein was assessed in a xenograft mouse model.Results: Rhein significantly inhibited CRC cell growth by inducing S phase cell cycle arrest and apoptosis. It also inhibited CRC cell migration and invasion ability through EMT process. mTOR was highly expression in CRC cancer tissues and cells exhibited high mTOR expression. Overexpression of mTOR promoted cell growth, migration, and invasion ability, whereas mTOR knockdown diminished these phenomena of CRC cells in vitro. Moreover, rhein directly targeted mTOR and suppressed the mTOR/p70S6K signaling pathway in CRC cells. Intraperitoneal administration of rhein inhibited CRC cell HCT116 xenograft tumor growth through the mTOR/p70S6K pathway.Conclusions: Rhein exerted anticancer activity in vitro and in vivo through directly targeting mTOR and inhibiting mTOR/p70S6K signaling pathway. These data indicate that rhein is a potent anticancer agent that could be useful for the prevention or treatment of CRC.

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Tunicamycin inhibits colon carcinoma growth and aggressiveness via modulation of the ERK-JNK-mediated AKT/mTOR signaling pathway

Cited by 18 publications

References 41 publications

Antitumor effects of Xi Huang pills on MDA‑MB‑231 cells in�vitro and in�vivo

Antitumor effects of Xi Huang pills on MDA‑MB‑231 cells in�vitro and in�vivo

Prophylactic role of Lactobacillus Paracasei exopolysaccharides on colon cancer cells through apoptosis not ferroptosis

Natural compound rhein suppresses colorectal cancer cells growth through mTOR/p70S6 kinase pathway in vitro and in vivo

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