Dataset Information

VERU-111 suppresses tumor growth and metastatic phenotypes of cervical cancer cells through the activation of p53 signaling pathway.

ABSTRACT: In this study, we investigated the therapeutic efficacy of VERU-111 in vitro and in vivo model systems of cervical cancer. VERU-111 treatment inhibited cell proliferation and, clonogenic potential, induce accumulation of p53 and down regulated the expression of HPV E6/E7 expression in cervical cancer cells. In addition, VERU-111 treatment also decreased the phosphorylation of Jak2^{(Tyr1007/1008)} and STAT3 at Tyr705 and Ser727. VERU-111 treatment arrested cell cycle in the G2/M phase and modulated cell cycle regulatory proteins (cyclin B1, p21, p34^cdc2 and pcdk1). Moreover, VERU-111 treatment induced apoptosis and modulated the expression of Bid, Bcl-xl, Survivin, Bax, Bcl2 and cleavage in PARP. In functional assays, VERU-111 markedly reduced the migratory and invasive potential of cervical cancer cells via modulations of MMPs. VERU-111 treatment also showed significant (P < 0.05) inhibition of orthotopic xenograft tumor growth in athymic nude mice. Taken together, our results demonstrate the potent anti-cancer efficacy of VERU-111 in experimental cervical cancer models.Thus, VERU-111 can be explored as a promising therapeutic agent for the treatment of cervical cancer.

SUBMITTER: Kashyap VK

PROVIDER: S-EPMC8059100 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

VERU-111 suppresses tumor growth and metastatic phenotypes of cervical cancer cells through the activation of p53 signaling pathway.

Kashyap Vivek K VK Dan Nirnoy N Chauhan Neeraj N Wang Qinghui Q Setua Saini S Nagesh Prashanth K B PKB Malik Shabnam S Batra Vivek V Yallapu Murali M MM Miller Duane D DD Li Wei W Hafeez Bilal B BB Jaggi Meena M Chauhan Subhash C SC

Cancer letters 20191203

In this study, we investigated the therapeutic efficacy of VERU-111 in vitro and in vivo model systems of cervical cancer. VERU-111 treatment inhibited cell proliferation and, clonogenic potential, induce accumulation of p53 and down regulated the expression of HPV E6/E7 expression in cervical cancer cells. In addition, VERU-111 treatment also decreased the phosphorylation of Jak2<sup>(Tyr1007/1008)</sup> and STAT3 at Tyr705 and Ser727. VERU-111 treatment arrested cell cycle in the G2/M phase an ...[more]

PMID: 31809801

Similar Datasets

Project description:Triple-negative breast cancer (TNBC) accounts for approximately 15% of breast cancer cases in the United States. TNBC has poorer overall prognosis relative to other molecular subtypes due to rapid onset of drug resistance to conventional chemotherapies and increased risk of visceral metastases. Taxanes like paclitaxel are standard chemotherapies that stabilize microtubules, but their clinical efficacy is often limited by drug resistance and neurotoxicities. We evaluated the preclinical efficacy of a novel, potent, and orally bioavailable tubulin inhibitor, VERU-111, in TNBC models. VERU-111 showed potent cytotoxicity against TNBC cell lines, inducing apoptosis and cell-cycle arrest in a concentration-dependent manner. VERU-111 also efficiently inhibited colony formation, cell migration, and invasion. Orally administered VERU-111 inhibited MDA-MB-231 xenograft growth in a dose-dependent manner, with similar efficacies to paclitaxel, but without acute toxicity. VERU-111 significantly reduced metastases originating from the mammary fat pad into lung, liver, and kidney metastasis in an experimental metastasis model. Moreover, VERU-111, but not paclitaxel, suppressed growth of luciferase-labeled, taxane-resistant, patient-derived metastatic TNBC tumors. In this model, VERU-111 repressed growth of preestablished axillary lymph node metastases and lung, bone, and liver metastases at study endpoint, whereas paclitaxel enhanced liver metastases relative to vehicle controls. Collectively, these studies strongly suggest that VERU-111 is not only a potent inhibitor of aggressive TNBC phenotypes, but it is also efficacious in a taxane-resistant model of metastatic TNBC. Thus, VERU-111 is a promising new generation of tubulin inhibitor for the treatment of TNBC and may be effective in patients who progress on taxanes.Results presented in this study demonstrate the efficacy of VERU-111 in vivo and provide strong rationale for future development of VERU-111 as an effective treatment for metastatic breast cancer.

Dataset Information

VERU-111 suppresses tumor growth and metastatic phenotypes of cervical cancer cells through the activation of p53 signaling pathway.

Publications

VERU-111 suppresses tumor growth and metastatic phenotypes of cervical cancer cells through the activation of p53 signaling pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets