Synthesis and biological evaluation of a novel anticancer agent CBISC that induces DNA damage response and diminishes levels of mutant-p53

Conor T. Ronayne; Sravan K. Jonnalagadda; Shirisha Jonnalagadda; Grady L. Nelson; Lucas N. Solano; Hithardha Palle; Chinnadurai Mani; Jon Rumbley; Jon Holy; Venkatram R. Mereddy

doi:10.1016/j.bbrc.2021.05.062

Synthesis and biological evaluation of a novel anticancer agent CBISC that induces DNA damage response and diminishes levels of mutant-p53

Conor T. Ronayne
, Sravan K. Jonnalagadda
, Shirisha Jonnalagadda
, Grady L. Nelson
, Lucas N. Solano
, Hithardha Palle
, Chinnadurai Mani
, Jon Rumbley
, Jon Holy
, Venkatram R. Mereddy

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

2 Scopus citations

Abstract

A novel nitrogen mustard CBISC has been synthesized and evaluated as an anticancer agent. CBISC has been shown to exhibit enhanced cell proliferation inhibition properties against mutant p53 cell lines colorectal cancer WiDr, pancreatic cancer (MIAPaCa-2 and PANC-1), and triple negative breast cancer (MDA-MB-231 and MDA-MB-468). In vitro mechanism of action studies revealed perturbations in the p53 pathway and increased cell death as evidenced by western blotting, immunofluorescent microscopy and MTT assay. Further, in vivo studies revealed that CBISC is well tolerated in healthy mice and exhibited significant in vivo tumor growth inhibition properties in WiDr and MIAPaCa-2 xenograft models. These studies illustrate the potential utility of CBISC as an anticancer agent.

Original language	English (US)
Pages (from-to)	127-132
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	562
DOIs	https://doi.org/10.1016/j.bbrc.2021.05.062
State	Published - Jul 12 2021

Bibliographical note

Funding Information:
This work was supported by University of Minnesota Duluth ; Whiteside Clinical Research Institute, Minnesota , and Randy Shaver Cancer Research and Community Fund, Minnesota .

Publisher Copyright:
© 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Alkylating agent
Apoptosis
DNA-damage
MIAPaCa-2
Mutant p53
WiDr

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10.1016/j.bbrc.2021.05.062

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Ronayne, C. T., Jonnalagadda, S. K., Jonnalagadda, S., Nelson, G. L., Solano, L. N., Palle, H., Mani, C., Rumbley, J., Holy, J., & Mereddy, V. R. (2021). Synthesis and biological evaluation of a novel anticancer agent CBISC that induces DNA damage response and diminishes levels of mutant-p53. Biochemical and Biophysical Research Communications, 562, 127-132. https://doi.org/10.1016/j.bbrc.2021.05.062

Synthesis and biological evaluation of a novel anticancer agent CBISC that induces DNA damage response and diminishes levels of mutant-p53. / Ronayne, Conor T.; Jonnalagadda, Sravan K.; Jonnalagadda, Shirisha et al.
In: Biochemical and Biophysical Research Communications, Vol. 562, 12.07.2021, p. 127-132.

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

Ronayne, CT, Jonnalagadda, SK, Jonnalagadda, S, Nelson, GL, Solano, LN, Palle, H, Mani, C, Rumbley, J, Holy, J & Mereddy, VR 2021, 'Synthesis and biological evaluation of a novel anticancer agent CBISC that induces DNA damage response and diminishes levels of mutant-p53', Biochemical and Biophysical Research Communications, vol. 562, pp. 127-132. https://doi.org/10.1016/j.bbrc.2021.05.062

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title = "Synthesis and biological evaluation of a novel anticancer agent CBISC that induces DNA damage response and diminishes levels of mutant-p53",

abstract = "A novel nitrogen mustard CBISC has been synthesized and evaluated as an anticancer agent. CBISC has been shown to exhibit enhanced cell proliferation inhibition properties against mutant p53 cell lines colorectal cancer WiDr, pancreatic cancer (MIAPaCa-2 and PANC-1), and triple negative breast cancer (MDA-MB-231 and MDA-MB-468). In vitro mechanism of action studies revealed perturbations in the p53 pathway and increased cell death as evidenced by western blotting, immunofluorescent microscopy and MTT assay. Further, in vivo studies revealed that CBISC is well tolerated in healthy mice and exhibited significant in vivo tumor growth inhibition properties in WiDr and MIAPaCa-2 xenograft models. These studies illustrate the potential utility of CBISC as an anticancer agent.",

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author = "Ronayne, \{Conor T.\} and Jonnalagadda, \{Sravan K.\} and Shirisha Jonnalagadda and Nelson, \{Grady L.\} and Solano, \{Lucas N.\} and Hithardha Palle and Chinnadurai Mani and Jon Rumbley and Jon Holy and Mereddy, \{Venkatram R.\}",

note = "Funding Information: This work was supported by University of Minnesota Duluth ; Whiteside Clinical Research Institute, Minnesota , and Randy Shaver Cancer Research and Community Fund, Minnesota . Publisher Copyright: {\textcopyright} 2021",

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doi = "10.1016/j.bbrc.2021.05.062",

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AU - Ronayne, Conor T.

AU - Jonnalagadda, Sravan K.

AU - Jonnalagadda, Shirisha

AU - Nelson, Grady L.

AU - Solano, Lucas N.

AU - Palle, Hithardha

AU - Mani, Chinnadurai

AU - Rumbley, Jon

AU - Holy, Jon

AU - Mereddy, Venkatram R.

N1 - Funding Information: This work was supported by University of Minnesota Duluth ; Whiteside Clinical Research Institute, Minnesota , and Randy Shaver Cancer Research and Community Fund, Minnesota . Publisher Copyright: © 2021

PY - 2021/7/12

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N2 - A novel nitrogen mustard CBISC has been synthesized and evaluated as an anticancer agent. CBISC has been shown to exhibit enhanced cell proliferation inhibition properties against mutant p53 cell lines colorectal cancer WiDr, pancreatic cancer (MIAPaCa-2 and PANC-1), and triple negative breast cancer (MDA-MB-231 and MDA-MB-468). In vitro mechanism of action studies revealed perturbations in the p53 pathway and increased cell death as evidenced by western blotting, immunofluorescent microscopy and MTT assay. Further, in vivo studies revealed that CBISC is well tolerated in healthy mice and exhibited significant in vivo tumor growth inhibition properties in WiDr and MIAPaCa-2 xenograft models. These studies illustrate the potential utility of CBISC as an anticancer agent.

AB - A novel nitrogen mustard CBISC has been synthesized and evaluated as an anticancer agent. CBISC has been shown to exhibit enhanced cell proliferation inhibition properties against mutant p53 cell lines colorectal cancer WiDr, pancreatic cancer (MIAPaCa-2 and PANC-1), and triple negative breast cancer (MDA-MB-231 and MDA-MB-468). In vitro mechanism of action studies revealed perturbations in the p53 pathway and increased cell death as evidenced by western blotting, immunofluorescent microscopy and MTT assay. Further, in vivo studies revealed that CBISC is well tolerated in healthy mice and exhibited significant in vivo tumor growth inhibition properties in WiDr and MIAPaCa-2 xenograft models. These studies illustrate the potential utility of CBISC as an anticancer agent.

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KW - Apoptosis

KW - DNA-damage

KW - MIAPaCa-2

KW - Mutant p53

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Synthesis and biological evaluation of a novel anticancer agent CBISC that induces DNA damage response and diminishes levels of mutant-p53

Abstract

Bibliographical note

UN SDGs

Keywords

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