Abstract

Modified forms of citrus pectin possess anticancer properties. However, their mechanism of action and the structural features involved remain unclear. Here, we showed that citrus pectin modified by heat treatment displayed cytotoxic effects in cancer cells. A fractionation approach was used aiming to identify active molecules. Dialysis and ethanol precipitation followed by HPLC analysis evidenced that most of the activity was related to molecules with molecular weight corresponding to low degree of polymerization oligogalacturonic acid. Heat-treatment of galacturonic acid also generated cytotoxic molecules. Furthermore, heat-modified galacturonic acid and heat-fragmented pectin contained the same molecule that induced cell death when isolated by HPLC separation. Mass spectrometry analyses revealed that 4,5-dihydroxy-2-cyclopenten-1-one was one cytotoxic molecule present in heat-treated pectin. Finally, we synthesized the enantiopure (4R,5R)-4,5-dihydroxy-2-cyclopenten-1-one and demonstrated that this molecule was cytotoxic and induced a similar pattern of apoptotic-like features than heat-modified pectin.

Original languageEnglish
Pages (from-to)39-51
Number of pages13
JournalCarbohydrate Polymers
Volume137
DOIs
Publication statusPublished - 2016

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Molecules
Acids
Heat treatment
Dialysis
Cell death
Fractionation
Mass spectrometry
citrus pectin
Hot Temperature
Ethanol
Molecular weight
Polymerization
Cells
pectin
galacturonic acid
cyclopentenone

Keywords

  • 4,5-Dihydroxy-2-cyclopenten-1-one
  • Cancer
  • Cytotoxic activity
  • Fragmented pectin

Cite this

@article{6e55d51320814d10b5dee9644dc889b0,
title = "Identification of a cytotoxic molecule in heat-modified citrus pectin",
abstract = "Modified forms of citrus pectin possess anticancer properties. However, their mechanism of action and the structural features involved remain unclear. Here, we showed that citrus pectin modified by heat treatment displayed cytotoxic effects in cancer cells. A fractionation approach was used aiming to identify active molecules. Dialysis and ethanol precipitation followed by HPLC analysis evidenced that most of the activity was related to molecules with molecular weight corresponding to low degree of polymerization oligogalacturonic acid. Heat-treatment of galacturonic acid also generated cytotoxic molecules. Furthermore, heat-modified galacturonic acid and heat-fragmented pectin contained the same molecule that induced cell death when isolated by HPLC separation. Mass spectrometry analyses revealed that 4,5-dihydroxy-2-cyclopenten-1-one was one cytotoxic molecule present in heat-treated pectin. Finally, we synthesized the enantiopure (4R,5R)-4,5-dihydroxy-2-cyclopenten-1-one and demonstrated that this molecule was cytotoxic and induced a similar pattern of apoptotic-like features than heat-modified pectin.",
keywords = "4,5-Dihydroxy-2-cyclopenten-1-one, Cancer, Cytotoxic activity, Fragmented pectin",
author = "Lionel Leclere and Maude Fransolet and Pierre Cambier and {El Bkassiny}, Sandy and Abdellatif Tikad and Marc Dieu and Vincent, {St{\'e}phane P.} and {Van Cutsem}, Pierre and Carine Michiels",
year = "2016",
doi = "10.1016/j.carbpol.2015.10.055",
language = "English",
volume = "137",
pages = "39--51",
journal = "Carbohydrate Polymers",
issn = "0144-8617",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Identification of a cytotoxic molecule in heat-modified citrus pectin

AU - Leclere, Lionel

AU - Fransolet, Maude

AU - Cambier, Pierre

AU - El Bkassiny, Sandy

AU - Tikad, Abdellatif

AU - Dieu, Marc

AU - Vincent, Stéphane P.

AU - Van Cutsem, Pierre

AU - Michiels, Carine

PY - 2016

Y1 - 2016

N2 - Modified forms of citrus pectin possess anticancer properties. However, their mechanism of action and the structural features involved remain unclear. Here, we showed that citrus pectin modified by heat treatment displayed cytotoxic effects in cancer cells. A fractionation approach was used aiming to identify active molecules. Dialysis and ethanol precipitation followed by HPLC analysis evidenced that most of the activity was related to molecules with molecular weight corresponding to low degree of polymerization oligogalacturonic acid. Heat-treatment of galacturonic acid also generated cytotoxic molecules. Furthermore, heat-modified galacturonic acid and heat-fragmented pectin contained the same molecule that induced cell death when isolated by HPLC separation. Mass spectrometry analyses revealed that 4,5-dihydroxy-2-cyclopenten-1-one was one cytotoxic molecule present in heat-treated pectin. Finally, we synthesized the enantiopure (4R,5R)-4,5-dihydroxy-2-cyclopenten-1-one and demonstrated that this molecule was cytotoxic and induced a similar pattern of apoptotic-like features than heat-modified pectin.

AB - Modified forms of citrus pectin possess anticancer properties. However, their mechanism of action and the structural features involved remain unclear. Here, we showed that citrus pectin modified by heat treatment displayed cytotoxic effects in cancer cells. A fractionation approach was used aiming to identify active molecules. Dialysis and ethanol precipitation followed by HPLC analysis evidenced that most of the activity was related to molecules with molecular weight corresponding to low degree of polymerization oligogalacturonic acid. Heat-treatment of galacturonic acid also generated cytotoxic molecules. Furthermore, heat-modified galacturonic acid and heat-fragmented pectin contained the same molecule that induced cell death when isolated by HPLC separation. Mass spectrometry analyses revealed that 4,5-dihydroxy-2-cyclopenten-1-one was one cytotoxic molecule present in heat-treated pectin. Finally, we synthesized the enantiopure (4R,5R)-4,5-dihydroxy-2-cyclopenten-1-one and demonstrated that this molecule was cytotoxic and induced a similar pattern of apoptotic-like features than heat-modified pectin.

KW - 4,5-Dihydroxy-2-cyclopenten-1-one

KW - Cancer

KW - Cytotoxic activity

KW - Fragmented pectin

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U2 - 10.1016/j.carbpol.2015.10.055

DO - 10.1016/j.carbpol.2015.10.055

M3 - Article

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JO - Carbohydrate Polymers

JF - Carbohydrate Polymers

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