Molecular targeting of H/MDM-2 oncoprotein 7in human colon cancer cells and stem-like colonic epithelial-derived progenitor cells

ANUSHA THADI; WILLIAM F. MORANO; MARIAN KHALILI; BLAKE D. BABCOCK; MOHAMMAD F. SHAIKH; DESHKA S. FOSTER; YELENA PIAZZA; ELIZABETH M. GLEESON; EVE GOLDSTEIN; LINDSAY STEELE; PAUL M. CAMPBELL; BO LIN; MATTHEW R. PINCUS; WILBUR B. BOWNE

doi:10.21873/anticanres.14749

Molecular targeting of H/MDM-2 oncoprotein 7in human colon cancer cells and stem-like colonic epithelial-derived progenitor cells

ANUSHA THADI, WILLIAM F. MORANO, MARIAN KHALILI, BLAKE D. BABCOCK, MOHAMMAD F. SHAIKH, DESHKA S. FOSTER, YELENA PIAZZA, ELIZABETH M. GLEESON, EVE GOLDSTEIN, LINDSAY STEELE, PAUL M. CAMPBELL, BO LIN, MATTHEW R. PINCUS, WILBUR B. BOWNE

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

5 Scopus citations

Abstract

Background/Aim: We have tested whether the anticancer peptide, PNC-27, that kills cancer cells but not normal cells by binding to cancer cell membrane HDM-2 forming pores, kills CD44+ colon cancer stem cells. Materials and Methods: Flow cytometry determined the CD44 and HDM-2 expression on six-colon cancer cell lines and one normal cell line (CCD- 18Co). MTT, LDH release, annexin V binding and caspase 3 assays were used to assess PNC-27-induced cell death. Bioluminescence imaging measured PNC-27 effects on in vivo tumor growth. Results: High percentages of cells in all six tumor lines expressed CD44. PNC-27 co-localized with membrane HDM-2 only in the cancer cells and caused total cell death (tumor cell necrosis, high LDH release, negative annexin V and caspase 3). In vivo, PNC-27 caused necrosis of tumor nodules but not of normal tissue. Conclusion: PNC-27 selectively kills colon cancer stem cells by binding of this peptide to membrane H/MDM-2.

Original language	English
Pages (from-to)	27-42
Number of pages	16
Journal	Anticancer Research
Volume	41
Issue number	1
DOIs	https://doi.org/10.21873/anticanres.14749
State	Published - Jan 2021
Externally published	Yes

Keywords

Cancer stem cells
H/MDM-2
PNC-27
Peritoneal carcinomatosis
Tumor cell necrosis

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10.21873/anticanres.14749

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THADI, ANUSHA., MORANO, WILLIAM. F., KHALILI, MARIAN., BABCOCK, BLAKE. D., SHAIKH, MOHAMMAD. F., FOSTER, DESHKA. S., PIAZZA, YELENA., GLEESON, ELIZABETH. M., GOLDSTEIN, EVE., STEELE, LINDSAY., CAMPBELL, PAUL. M., LIN, BO., PINCUS, MATTHEW. R., & BOWNE, WILBUR. B. (2021). Molecular targeting of H/MDM-2 oncoprotein 7in human colon cancer cells and stem-like colonic epithelial-derived progenitor cells. Anticancer Research, 41(1), 27-42. https://doi.org/10.21873/anticanres.14749

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title = "Molecular targeting of H/MDM-2 oncoprotein 7in human colon cancer cells and stem-like colonic epithelial-derived progenitor cells",

abstract = "Background/Aim: We have tested whether the anticancer peptide, PNC-27, that kills cancer cells but not normal cells by binding to cancer cell membrane HDM-2 forming pores, kills CD44+ colon cancer stem cells. Materials and Methods: Flow cytometry determined the CD44 and HDM-2 expression on six-colon cancer cell lines and one normal cell line (CCD- 18Co). MTT, LDH release, annexin V binding and caspase 3 assays were used to assess PNC-27-induced cell death. Bioluminescence imaging measured PNC-27 effects on in vivo tumor growth. Results: High percentages of cells in all six tumor lines expressed CD44. PNC-27 co-localized with membrane HDM-2 only in the cancer cells and caused total cell death (tumor cell necrosis, high LDH release, negative annexin V and caspase 3). In vivo, PNC-27 caused necrosis of tumor nodules but not of normal tissue. Conclusion: PNC-27 selectively kills colon cancer stem cells by binding of this peptide to membrane H/MDM-2.",

keywords = "Cancer stem cells, H/MDM-2, PNC-27, Peritoneal carcinomatosis, Tumor cell necrosis",

author = "ANUSHA THADI and MORANO, {WILLIAM F.} and MARIAN KHALILI and BABCOCK, {BLAKE D.} and SHAIKH, {MOHAMMAD F.} and FOSTER, {DESHKA S.} and YELENA PIAZZA and GLEESON, {ELIZABETH M.} and EVE GOLDSTEIN and LINDSAY STEELE and CAMPBELL, {PAUL M.} and BO LIN and PINCUS, {MATTHEW R.} and BOWNE, {WILBUR B.}",

year = "2021",

month = jan,

doi = "10.21873/anticanres.14749",

language = "English",

volume = "41",

pages = "27--42",

journal = "Anticancer Research",

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THADI, ANUSHA, MORANO, WILLIAMF, KHALILI, MARIAN, BABCOCK, BLAKED, SHAIKH, MOHAMMADF, FOSTER, DESHKAS, PIAZZA, YELENA, GLEESON, ELIZABETHM, GOLDSTEIN, EVE, STEELE, LINDSAY, CAMPBELL, PAULM, LIN, BO, PINCUS, MATTHEWR & BOWNE, WILBURB 2021, 'Molecular targeting of H/MDM-2 oncoprotein 7in human colon cancer cells and stem-like colonic epithelial-derived progenitor cells', Anticancer Research, vol. 41, no. 1, pp. 27-42. https://doi.org/10.21873/anticanres.14749

TY - JOUR

T1 - Molecular targeting of H/MDM-2 oncoprotein 7in human colon cancer cells and stem-like colonic epithelial-derived progenitor cells

AU - THADI, ANUSHA

AU - MORANO, WILLIAM F.

AU - KHALILI, MARIAN

AU - BABCOCK, BLAKE D.

AU - SHAIKH, MOHAMMAD F.

AU - FOSTER, DESHKA S.

AU - PIAZZA, YELENA

AU - GLEESON, ELIZABETH M.

AU - GOLDSTEIN, EVE

AU - STEELE, LINDSAY

AU - CAMPBELL, PAUL M.

AU - LIN, BO

AU - PINCUS, MATTHEW R.

AU - BOWNE, WILBUR B.

PY - 2021/1

Y1 - 2021/1

N2 - Background/Aim: We have tested whether the anticancer peptide, PNC-27, that kills cancer cells but not normal cells by binding to cancer cell membrane HDM-2 forming pores, kills CD44+ colon cancer stem cells. Materials and Methods: Flow cytometry determined the CD44 and HDM-2 expression on six-colon cancer cell lines and one normal cell line (CCD- 18Co). MTT, LDH release, annexin V binding and caspase 3 assays were used to assess PNC-27-induced cell death. Bioluminescence imaging measured PNC-27 effects on in vivo tumor growth. Results: High percentages of cells in all six tumor lines expressed CD44. PNC-27 co-localized with membrane HDM-2 only in the cancer cells and caused total cell death (tumor cell necrosis, high LDH release, negative annexin V and caspase 3). In vivo, PNC-27 caused necrosis of tumor nodules but not of normal tissue. Conclusion: PNC-27 selectively kills colon cancer stem cells by binding of this peptide to membrane H/MDM-2.

AB - Background/Aim: We have tested whether the anticancer peptide, PNC-27, that kills cancer cells but not normal cells by binding to cancer cell membrane HDM-2 forming pores, kills CD44+ colon cancer stem cells. Materials and Methods: Flow cytometry determined the CD44 and HDM-2 expression on six-colon cancer cell lines and one normal cell line (CCD- 18Co). MTT, LDH release, annexin V binding and caspase 3 assays were used to assess PNC-27-induced cell death. Bioluminescence imaging measured PNC-27 effects on in vivo tumor growth. Results: High percentages of cells in all six tumor lines expressed CD44. PNC-27 co-localized with membrane HDM-2 only in the cancer cells and caused total cell death (tumor cell necrosis, high LDH release, negative annexin V and caspase 3). In vivo, PNC-27 caused necrosis of tumor nodules but not of normal tissue. Conclusion: PNC-27 selectively kills colon cancer stem cells by binding of this peptide to membrane H/MDM-2.

KW - Cancer stem cells

KW - H/MDM-2

KW - PNC-27

KW - Peritoneal carcinomatosis

KW - Tumor cell necrosis

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U2 - 10.21873/anticanres.14749

DO - 10.21873/anticanres.14749

M3 - Article

C2 - 33419797

AN - SCOPUS:85099699993

SN - 0250-7005

VL - 41

SP - 27

EP - 42

JO - Anticancer Research

JF - Anticancer Research

IS - 1

ER -

Molecular targeting of H/MDM-2 oncoprotein 7in human colon cancer cells and stem-like colonic epithelial-derived progenitor cells

Abstract

Keywords

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