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.