title: Heat-modified citrus pectin induces apoptosis-like cell death and autophagy in HepG2 and A549 cancer cells.
abstract: Cancer is still one of the leading causes of death worldwide, and finding new treatments remains a major challenge. Previous studies showed that modified forms of pectin, a complex polysaccharide present in the primary plant cell wall, possess anticancer properties. Nevertheless, the mechanism of action of modified pectin and the pathways involved are unclear. Here, we show that citrus pectin modified by heat treatment induced cell death in HepG2 and A549 cells. The induced cell death differs from classical apoptosis because no DNA cleavage was observed. In addition, Z-VAD-fmk, a pan-caspase inhibitor, did not influence the observed cell death in HepG2 cells but appeared to be partly protective in A549 cells, indicating that heat-modified citrus pectin might induce caspase-independent cell death. An increase in the abundance of the phosphatidylethanolamine-conjugated Light Chain 3 (LC3) protein and a decrease in p62 protein abundance were observed in both cell types when incubated in the presence of heat-modified citrus pectin. These results indicate the activation of autophagy. To our knowledge, this is the first time that autophagy has been revealed in cells incubated in the presence of a modified form of pectin. This autophagy activation appears to be protective, at least for A549 cells, because its inhibition with 3-methyladenine increased the observed modified pectin-induced cytotoxicity. This study confirms the potential of modified pectin to improve chemotherapeutic cancer treatments.
authors: Laboratory of Biochemistry and Cellular Biology-URBC, NARILIS, University of Namur, 61 rue de Bruxelles, 5000, Namur, Belgium.
authors: Lionel
authors: L
authors: Leclere
authors: Laboratory of Biochemistry and Cellular Biology-URBC, NARILIS, University of Namur, 61 rue de Bruxelles, 5000, Namur, Belgium.
authors: Maude
authors: M
authors: Fransolet
authors: Laboratory of Biochemistry and Cellular Biology-URBC, NARILIS, University of Namur, 61 rue de Bruxelles, 5000, Namur, Belgium.
authors: Francois
authors: F
authors: Cote
authors: Laboratory of Plant Cellular Biology-URBV, University of Namur, 61 rue de Bruxelles, 5000, Namur, Belgium.
authors: Pierre
authors: P
authors: Cambier
authors: Laboratory of Biochemistry and Cellular Biology-URBC, NARILIS, University of Namur, 61 rue de Bruxelles, 5000, Namur, Belgium.
authors: Thierry
authors: T
authors: Arnould
authors: Laboratory of Plant Cellular Biology-URBV, University of Namur, 61 rue de Bruxelles, 5000, Namur, Belgium.
authors: Pierre
authors: P
authors: Van Cutsem
authors: Laboratory of Biochemistry and Cellular Biology-URBC, NARILIS, University of Namur, 61 rue de Bruxelles, 5000, Namur, Belgium.
authors: Carine
authors: C
authors: Michiels
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D006358:Hot Temperature; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D008840:Microfilament Proteins / Q000378:metabolism; D010368:Pectins / Q000494:pharmacology*; D054875:Ubiquitination / Q000187:drug effects; D013049:Spectrin
chemical_list: D000225:Adenine; D002352:Carrier Proteins; D061945:Caspase Inhibitors; D020169:Caspases; D018942:Macrolides; D008840:Microfilament Proteins; D010368:Pectins; D013049:Spectrin; C057620:bafilomycin A; C586814:citrus pectin; C025946:3-methyladenine