Effects of aged garlic extract may differ between normal cells and cancer cells

Aged garlic extract (AGE) is one of the widely used garlic-based products that are extensively studied and are commercially available. However, there are no reports that compare the effects of AGE on normal cells and oral cancer cells. The present study tried to investigate the effects of AGE on normal healthy cells and cancer cells. The effect of AGE on the proliferation of normal cell lines HaCaT and fibroblast, in addition to cancer cell lines SCC7, HSC2, HSC3 and Ca9-22 were evaluated by MTT assay. The effects of AGE on cell migration were examined using wound healing and migration assays. Whole transcriptome analysis, ingenuity pathways analysis (IPA) and western blot analysis were used to investigate the mechanism of action of AGE in HaCaT and SCC7 cells. Data from the aforementioned assays were then evaluated and compared to assess if AGE affects normal cells differently compared with cancer cells. AGE was found to promote the proliferation and migration of normal cells, especially HaCaT, in the absence of FBS more markedly compared with those of cancer cells. However, AGE could not promote wound healing in fibroblast cells at the same rate as in HaCaT cells. In normal cells, sequential or combination AGE treatment with 5-fluorouracil (5-FU), cisplatin (CDDP) and docetaxel (DOC) somewhat counteracted the proliferation-limiting effects of anti-cancer agents. However, in cancer cells, AGE treatments enhanced the inhibitory effects of anti-cancer agents when used in combination with 5-FU, CDDP or DOC. This observation was more evident in the case of pre-treatment with anticancer agents followed by AGE sequential treatment. Subsequently, whole transcriptome analysis and IPA data suggested that AGE facilitated the proliferation and survival of normal cells through the induction of protein kinase B family protein and brain-derived neurotrophic factor pathways, whilst suppressing ferroptosis These data were also confirmed by western blotting to see if the genetic changes shown in whole transcriptome analysis and IPA are also induced at the protein level. In addition, AGE may reduce cancer cell proliferation through the suppression of cancer metastasis signaling and enhancement of phagocytic activity according to whole transcriptome analysis and IPA data. Taken together, these findings suggested that AGE may prompt the proliferation of normal cells and suppress the that of cancer cells through different cellular processes and signaling pathways.