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Inhibition of T-type Calcium Channels Suppresses Cell Proliferation and Invasion of Medulloblastoma Cells via Alterations in Cell Metabolic Activities [Poster]

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Azimi, I, Inhibition of T-type Calcium Channels Suppresses Cell Proliferation and Invasion of Medulloblastoma Cells via Alterations in Cell Metabolic Activities [Poster], ANZCHOG Virtual21 Annual Scientific Meeting, 23-25 June 2021, Online Web Conference (2021) [Conference Extract]


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Official URL: https://anzchog.delegateconnect.co/talks/inhibitio...

Abstract

Medulloblastoma (MB) is the most common malignant childhood brain cancer. The low efficacy and long-lasting side effects of current therapies necessitate the need for a new treatment for MB. In this study, in-silico transcriptomics analysis of MB patients revealed a significant correlation of a CaV3 calcium channel expression with metastasis and patient survival rates. Pharmacological inhibition of CaV3 (T-type) calcium channels by mibefradil or NNC-55-0396 (NNC) significantly reduced MB cell proliferation and resistance to an MB chemotherapeutic agent, vincristine, as assessed by WST-1 proliferation assay. Mibefradil or NNC treatment further reduced the invasive abilities of MB cells in an agar invasion assay. These responses were specific to T-type calcium channel blockade as inhibition of L-type channels did not produce the same effects. Further studies showed an induction of apoptosis by mibefradil or NNC treatment in a concentration-dependent manner. Studies into the mechanism of action of these inhibitors revealed their effect on metabolic pathways of MB cells. Our results present the first evidence to the antitumor effects of mibefradil and NNC in medulloblastoma cells. This study provides insight into the future development of potential therapeutic approaches for MB that target the invasion, proliferation, and drug resistance in these cells.

Item Details

Item Type:Conference Extract
Keywords:brain cancer, medulloblastoma, t-type calcium channel, apoptosis, metabolism
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Basic pharmacology
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the health sciences
UTAS Author:Azimi, I (Dr Iman Azimi)
ID Code:151267
Year Published:2021
Deposited By:Pharmacy
Deposited On:2022-07-26
Last Modified:2022-07-28
Downloads:0

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