Synthesis of breast cancer targeting conjugate of temporin-SHa analog and its effect on pro- and anti-apoptotic protein expression in MCF-7 cells

Farzana Shaheen; Muhammad Nadeem-ul-Haque; Aqeel Ahmed; Shabana U. Simjee; A. Ganesan; Almas Jabeen; Zafar Ali Shah; M. Iqbal Choudhary

doi:10.1016/j.peptides.2018.07.002

Synthesis of breast cancer targeting conjugate of temporin-SHa analog and its effect on pro- and anti-apoptotic protein expression in MCF-7 cells

Farzana Shaheen, Muhammad Nadeem-ul-Haque, Aqeel Ahmed, Shabana U. Simjee, A. Ganesan, Almas Jabeen, Zafar Ali Shah, M. Iqbal Choudhary

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Abstract

The frog natural product temporin-SHa (FLSGIVGMLGKLFamide) is a potent antimicrobial peptide, as is the analog [S3K]SHa. By solid-phase synthesis, we prepared temporin-SHa and several temporin-SHa analogs with one or more D-alanine residues incorporated. The natural product and the analog [G10a]SHa were found to be cytotoxic in mammalian cell lines and induce cell death. To achieve selectivity, we conjugated the analog [G10a]SHa with a breast cancer targeting peptide (BCTP). The resulting peptide temporin [G10a]SHa-BCTP conjugate was selectively active against the MCF-7 breast cancer cell line with no cytotoxicity in NIH-3T3 fibroblasts. Unlike the natural product or [G10a]SHa, the conjugated peptide induced apoptosis, down regulating the expression of Bcl-2 and survivin and up regulating Bax and caspase-3.

Original language	English
Pages (from-to)	68-82
Number of pages	15
Journal	Peptides
Volume	106
Early online date	6 Jul 2018
DOIs	https://doi.org/10.1016/j.peptides.2018.07.002
Publication status	Published - Aug 2018

Keywords

antimicrobial peptides
temporin-SHa analogs
breast cancer targeting peptide conjugate
apoptosis
Bcl-2
survivin
caspase-3

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Access to Document

10.1016/j.peptides.2018.07.002

Accepted manuscriptAccepted author manuscript, 1.01 MBLicence: CC BY-NC-ND

https://linkinghub.elsevier.com/retrieve/pii/S0196978118301281

Cite this

@article{1ca5b378bb03400c806b3f24c07b0c17,

title = "Synthesis of breast cancer targeting conjugate of temporin-SHa analog and its effect on pro- and anti-apoptotic protein expression in MCF-7 cells",

abstract = "The frog natural product temporin-SHa (FLSGIVGMLGKLFamide) is a potent antimicrobial peptide, as is the analog [S3K]SHa. By solid-phase synthesis, we prepared temporin-SHa and several temporin-SHa analogs with one or more D-alanine residues incorporated. The natural product and the analog [G10a]SHa were found to be cytotoxic in mammalian cell lines and induce cell death. To achieve selectivity, we conjugated the analog [G10a]SHa with a breast cancer targeting peptide (BCTP). The resulting peptide temporin [G10a]SHa-BCTP conjugate was selectively active against the MCF-7 breast cancer cell line with no cytotoxicity in NIH-3T3 fibroblasts. Unlike the natural product or [G10a]SHa, the conjugated peptide induced apoptosis, down regulating the expression of Bcl-2 and survivin and up regulating Bax and caspase-3.",

keywords = "antimicrobial peptides, temporin-SHa analogs, breast cancer targeting peptide conjugate, apoptosis, Bcl-2, survivin, caspase-3",

author = "Farzana Shaheen and Muhammad Nadeem-ul-Haque and Aqeel Ahmed and Simjee, {Shabana U.} and A. Ganesan and Almas Jabeen and Shah, {Zafar Ali} and Choudhary, {M. Iqbal}",

year = "2018",

month = aug,

doi = "10.1016/j.peptides.2018.07.002",

language = "English",

volume = "106",

pages = "68--82",

journal = "Peptides",

issn = "0196-9781",

publisher = "Elsevier",

}

TY - JOUR

T1 - Synthesis of breast cancer targeting conjugate of temporin-SHa analog and its effect on pro- and anti-apoptotic protein expression in MCF-7 cells

AU - Shaheen, Farzana

AU - Nadeem-ul-Haque, Muhammad

AU - Ahmed, Aqeel

AU - Simjee, Shabana U.

AU - Ganesan, A.

AU - Jabeen, Almas

AU - Shah, Zafar Ali

AU - Choudhary, M. Iqbal

PY - 2018/8

Y1 - 2018/8

N2 - The frog natural product temporin-SHa (FLSGIVGMLGKLFamide) is a potent antimicrobial peptide, as is the analog [S3K]SHa. By solid-phase synthesis, we prepared temporin-SHa and several temporin-SHa analogs with one or more D-alanine residues incorporated. The natural product and the analog [G10a]SHa were found to be cytotoxic in mammalian cell lines and induce cell death. To achieve selectivity, we conjugated the analog [G10a]SHa with a breast cancer targeting peptide (BCTP). The resulting peptide temporin [G10a]SHa-BCTP conjugate was selectively active against the MCF-7 breast cancer cell line with no cytotoxicity in NIH-3T3 fibroblasts. Unlike the natural product or [G10a]SHa, the conjugated peptide induced apoptosis, down regulating the expression of Bcl-2 and survivin and up regulating Bax and caspase-3.

AB - The frog natural product temporin-SHa (FLSGIVGMLGKLFamide) is a potent antimicrobial peptide, as is the analog [S3K]SHa. By solid-phase synthesis, we prepared temporin-SHa and several temporin-SHa analogs with one or more D-alanine residues incorporated. The natural product and the analog [G10a]SHa were found to be cytotoxic in mammalian cell lines and induce cell death. To achieve selectivity, we conjugated the analog [G10a]SHa with a breast cancer targeting peptide (BCTP). The resulting peptide temporin [G10a]SHa-BCTP conjugate was selectively active against the MCF-7 breast cancer cell line with no cytotoxicity in NIH-3T3 fibroblasts. Unlike the natural product or [G10a]SHa, the conjugated peptide induced apoptosis, down regulating the expression of Bcl-2 and survivin and up regulating Bax and caspase-3.

KW - antimicrobial peptides

KW - temporin-SHa analogs

KW - breast cancer targeting peptide conjugate

KW - apoptosis

KW - Bcl-2

KW - survivin

KW - caspase-3

U2 - 10.1016/j.peptides.2018.07.002

DO - 10.1016/j.peptides.2018.07.002

M3 - Article

SN - 0196-9781

VL - 106

SP - 68

EP - 82

JO - Peptides

JF - Peptides

ER -