Inhibitory Effects of Indomethacin in Human MNNG/HOS Osteosarcoma Cell Line In Vitro

Saied Mirshahidi; Rosalia de Necochea-Campion; Annie Moretta; Nadine L. Williams; Mark E. Reeves; Salman Otoukesh; Hamid R. Mirshahidi; Shahrzad Khosrowpour; Penelope Duerksen-Hughes; Lee M. Zuckerman

doi:10.1080/07357907.2019.1698592

Inhibitory Effects of Indomethacin in Human MNNG/HOS Osteosarcoma Cell Line In Vitro

Saied Mirshahidi, Rosalia de Necochea-Campion, Annie Moretta, Nadine L. Williams, Mark E. Reeves, Salman Otoukesh, Hamid R. Mirshahidi, Shahrzad Khosrowpour, Penelope Duerksen-Hughes, Lee M. Zuckerman

Research output: Contribution to journal › Article › peer-review

Abstract

Recurrence or metastasis remains the major cause of poor prognosis and mortality in Osteosarcoma patients. Therefore, development of more effective therapeutic approaches is required. We showed that indomethacin, significantly induces apoptosis in MNNG/HOS cell line, which was confirmed by morphological changes, increased Annexin-V + cells and nuclear fragmentation. Apoptosis was accompanied by increased cleavage of caspase-3 and PARP, suggesting activation of caspase-dependent cell death. Indomethacin significantly decreased the expression of β-catenin, a key player in tumor metastasis. These results indicate that indomethacin may have the potential to be used as neoadjuvant or adjuvant treatment; however, additional studies are required.

Original language	English
Pages (from-to)	23-36
Number of pages	14
Journal	Cancer Investigation
Volume	38
Issue number	1
DOIs	https://doi.org/10.1080/07357907.2019.1698592
State	Published - Jan 2 2020

ASJC Scopus Subject Areas

Oncology
Cancer Research

Keywords

Osteosarcoma
apoptosis
caspase-dependent
indomethacin
nonsteroidal anti-inflammatory drug (NSAID)
Cyclooxygenase Inhibitors/pharmacology
Caspase 3/metabolism
Indomethacin/pharmacology
Prognosis
Poly(ADP-ribose) Polymerases/metabolism
Humans
Apoptosis/drug effects
Gene Expression Regulation, Neoplastic/drug effects
Cell Survival/drug effects
Osteosarcoma/drug therapy
beta Catenin/metabolism
Cell Line, Tumor
Bone Neoplasms/drug therapy
Drug Screening Assays, Antitumor

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title = "Inhibitory Effects of Indomethacin in Human MNNG/HOS Osteosarcoma Cell Line In Vitro",

abstract = "Recurrence or metastasis remains the major cause of poor prognosis and mortality in Osteosarcoma patients. Therefore, development of more effective therapeutic approaches is required. We showed that indomethacin, significantly induces apoptosis in MNNG/HOS cell line, which was confirmed by morphological changes, increased Annexin-V + cells and nuclear fragmentation. Apoptosis was accompanied by increased cleavage of caspase-3 and PARP, suggesting activation of caspase-dependent cell death. Indomethacin significantly decreased the expression of β-catenin, a key player in tumor metastasis. These results indicate that indomethacin may have the potential to be used as neoadjuvant or adjuvant treatment; however, additional studies are required.",

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author = "Saied Mirshahidi and {de Necochea-Campion}, Rosalia and Annie Moretta and Williams, {Nadine L.} and Reeves, {Mark E.} and Salman Otoukesh and Mirshahidi, {Hamid R.} and Shahrzad Khosrowpour and Penelope Duerksen-Hughes and Zuckerman, {Lee M.}",

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AU - Mirshahidi, Saied

AU - de Necochea-Campion, Rosalia

AU - Moretta, Annie

AU - Williams, Nadine L.

AU - Reeves, Mark E.

AU - Otoukesh, Salman

AU - Mirshahidi, Hamid R.

AU - Khosrowpour, Shahrzad

AU - Duerksen-Hughes, Penelope

AU - Zuckerman, Lee M.

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N2 - Recurrence or metastasis remains the major cause of poor prognosis and mortality in Osteosarcoma patients. Therefore, development of more effective therapeutic approaches is required. We showed that indomethacin, significantly induces apoptosis in MNNG/HOS cell line, which was confirmed by morphological changes, increased Annexin-V + cells and nuclear fragmentation. Apoptosis was accompanied by increased cleavage of caspase-3 and PARP, suggesting activation of caspase-dependent cell death. Indomethacin significantly decreased the expression of β-catenin, a key player in tumor metastasis. These results indicate that indomethacin may have the potential to be used as neoadjuvant or adjuvant treatment; however, additional studies are required.

AB - Recurrence or metastasis remains the major cause of poor prognosis and mortality in Osteosarcoma patients. Therefore, development of more effective therapeutic approaches is required. We showed that indomethacin, significantly induces apoptosis in MNNG/HOS cell line, which was confirmed by morphological changes, increased Annexin-V + cells and nuclear fragmentation. Apoptosis was accompanied by increased cleavage of caspase-3 and PARP, suggesting activation of caspase-dependent cell death. Indomethacin significantly decreased the expression of β-catenin, a key player in tumor metastasis. These results indicate that indomethacin may have the potential to be used as neoadjuvant or adjuvant treatment; however, additional studies are required.

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