CELLFOOD™ induces apoptosis in human mesothelioma and colorectal cancer cells by modulating p53, c-myc and pAkt signaling pathways

Nuvoli, Barbara; Santoro, Raffaela; Catalani, Simona; Battistelli, Serafina; Benedetti, Serena; Canestrari, Franco; Galati, Rossella

doi:10.1186/1756-9966-33-24

Cited by 17 publications

(12 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…c-myc is a transcription factor which governs cell proliferation and metastasis. Suppression of c-myc has been shown to have antiproliferative (33) and apoptotic (34) effect in mesothelioma. In addition, growth inhibition in APL by ATO was partially mediated through suppression of c-myc (35).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of thymidylate synthase and E2F1 by arsenic trioxide in mesothelioma

Lam¹,

Li²,

Zheng³

et al. 2014

International Journal of Oncology

View full text Add to dashboard Cite

Malignant pleural mesothelioma is a global health issue. Arsenic trioxide (ATO) has been shown to suppress thymidylate synthase (TYMS) in lung adenocarcinoma and colorectal cancer, and induce apoptosis in acute promyelocytic leukemia. With TYMS as a putative therapeutic target, the effect of ATO in mesothelioma was therefore studied. A panel of 5 mesothelioma cell lines was used to study the effect of ATO on cell viability, protein expression, mRNA expression and TYMS activity by MTT assay, western blot, qPCR and tritium-release assay, respectively. The knockdown of TYMS and E2F1 was performed with a specific siRNA. Phosphatidylserine externalization and mitochondrial membrane depolarization were measured by Annexin V and JC-1 staining respectively. The in vivo effect of ATO was studied using a nude mouse xenograft model. Application of ATO demonstrated anticancer effects in the cell line model with clinically achievable concentrations. Downregulation of TYMS protein (except H226 cells and 1.25 µM ATO in H2052 cells) and mRNA expression (H28 cells), pRB1 (H28 cells) and E2F1 and TYMS activity (except H226 cells) were also evident. E2F1 knockdown decreased cell viability more significantly than TYMS knockdown. In general, thymidine kinase 1, ribonucleotide reductase M1, c-myc and skp2 were downregulated by ATO. p-c-Jun was downregulated in H28 cells while upregulated in 211H cells. Phosphatidylserine externalization, mitochondrial membrane depolarization, downregulation of Bcl-2 and Bcl-xL, and upregulation of Bak and cleaved caspase-3 were observed. In the H226 xenograft model, the relative tumor growth was aborted, and E2F1 was downregulated while cleaved caspase-3 was elevated and localized to the nucleus in the ATO treatment group. ATO has potent antiproliferative and cytotoxic effects in mesothelioma in vitro and in vivo, partially mediated through E2F1 targeting (less effect through TYMS targeting). There is sound scientific evidence to support the clinical application of ATO in treatment of mesothelioma.

show abstract

Section: Discussionmentioning

confidence: 99%

Downregulation of thymidylate synthase and E2F1 by arsenic trioxide in mesothelioma

Lam¹,

Li²,

Zheng³

et al. 2014

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…However, for those with advanced/malignant CRC, the overall survival has not been remarkably prolonged [ 4 ]. Research groups are thus searching for novel and more efficient anti-CRC agents [ 1 , 2 , 5 – 7 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting sphingosine kinase 2 (SphK2) by ABC294640 inhibits colorectal cancer cell growth in vitro and in vivo

Cai

Chen

et al. 2015

J Exp Clin Cancer Res

View full text Add to dashboard Cite

BackgroundColorectal cancer (CRC) is a major health problem in China and around the world. It is one of the leading causes of cancer-related deaths. Research groups are thus searching for novel and more efficient anti-CRC agents.ResultsHere we demonstrated that ABC294640, a novel SphK2 inhibitor, induced growth inhibition and apoptosis in transformed and primary CRC cells. The SphK activity was remarkably inhibited by ABC294640, accompanied by sphingosine-1-phosphate (S1P) depletion and ceramide incensement in CRC cells. Exogenously-added S1P inhibited ABC294640-induced HT-29 cell lethality. While C6 ceramide and SphK1 inhibitor SKI-II facilitated ABC294640-induced cytotoxicity against HT-29 cells. ABC294640 inhibited AKT-S6K1, but activated JNK signaling in transformed and primary CRC cells. JNK inhibitors (SP600125 and JNKi-II) alleviated ABC294640-induced CRC cell apoptosis. Moreover, a low concentration of ABC294640 sensitized the activity of 5-FU and cisplatin in vitro. In vivo, ABC294640 oral administration dramatically inhibited HT-29 xenografts growth in nude mice.ConclusionsTargeting of SphK2 by ABC294640 potently inhibits CRC cell growth both in vitro and in vivo, ABC294640 could be developed as a novel therapeutic for the treatment of CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0205-y) contains supplementary material, which is available to authorized users.

show abstract

“…The involvement of this pathway in the development of colon cancer and metastasis, including cell proliferation, apoptosis and migration, has been extensively investigated (15)(16)(17)(18). Furthermore, the blockade of PI3K/Akt activity in colon cancer cells has shown promising anti-cancer effects (19)(20)(21)(22). Recent studies have demonstrated that the downstream factor of the PI3K/Akt pathway, the mammalian target of rapamycin (mTOR), is a potential therapeutic target in various types of cancer, including non-small cell lung cancer (23) (26), non-Hodgkin's lymphoma (27) and leukemia (28,29).…”

Section: Introductionmentioning

confidence: 99%

miR-218 inhibits the invasion and migration of colon cancer cells by targeting the PI3K/Akt/mTOR signaling pathway

Zhang

Shi

Tang

et al. 2015

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Abstract. Colon cancer is one of the most common and lethal malignancies worldwide. Despite major advances in the treatment of colon cancer, the prognosis remains very poor. Thus, novel and effective therapies for colon cancer are urgently needed. In the present study, the expression status of miR-218 and the role of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway were investigated in colon cancer samples. Firstly, we observed that miR-218 expression was significantly reduced, while PI3K/Akt/mTOR pathway activity was enhanced. The overexpression of miR-218 suppressed the proliferation, migration and invasion of LoVo colon cancer cells, whereas the inhibition of miR-218 promoted these processes. Furthermore, the PI3K/Akt/mTOR signaling pathway was identified as a direct target of miR-218. The upregulation of miR-218 inhibited the activation of the PI3K/Akt/mTOR signaling pathway, as well as the expression of matrix metalloproteinase (MMP)9. The downregulation of miR-218 activated the PI3K/Akt/mTOR signaling pathway and promoted MMP9 expression. Taken together, our results demonstrate that miR-218 suppresses the proliferation, migration and invasion of LoVo colon cancer cells by targeting the PI3K/Akt/mTOR signaling pathway and MMP9. Our data indicate that miR-218 is a potential target in the treatment of colon cancer.

show abstract

CELLFOOD™ induces apoptosis in human mesothelioma and colorectal cancer cells by modulating p53, c-myc and pAkt signaling pathways

Cited by 17 publications

References 57 publications

Downregulation of thymidylate synthase and E2F1 by arsenic trioxide in mesothelioma

Downregulation of thymidylate synthase and E2F1 by arsenic trioxide in mesothelioma

Targeting sphingosine kinase 2 (SphK2) by ABC294640 inhibits colorectal cancer cell growth in vitro and in vivo

miR-218 inhibits the invasion and migration of colon cancer cells by targeting the PI3K/Akt/mTOR signaling pathway

Contact Info

Product

Resources

About