**3. Unfolded Protein Response (UPR) Pathways**

The endoplasmic reticulum (ER) stress response, also known as unfolded protein response (UPR), is a cellular process that is activated by a number of conditions that disrupt protein folding in the ER. The UPR is an evolutionarily conserved adaptive mechanism in eukaryotic cells that aims to clear unfolded proteins and restore ER protein homeostasis. When ER stress is irreversible, cellular functions deteriorate, often leading to cell death (Figure 2) [93]. There is mounting evidence that ER stress plays a significant role in the development and progression of varied diseases, including cancer and inflammation [93,94]. FaDOH-induced cell death is mediated via ER stress induction and the activation of the UPR.

Reducing the extent of ER stress by overexpressing the ER chaperone protein glucoseregulated protein 78 (GRP78) or by knocking down components of the UPR pathway decreased FaDOH-induced apoptosis. In contrast, raising the level of ER stress by inhibiting GRP78 enhanced the apoptosis triggered by FaDOH extracted from *Oplopanax horridus* (*O. horridus*) [95]. In addition, ER stress mediated panaxydol-induced apoptosis in MCF-7 cells [96]. Another study investigated the effect of a sub-toxic dose of 5 μM of FaDOH in a series of experiments and found that it increased the lipid content and number of lipid droplets (LDs) in human mesenchymal stem cells (hMSCs) and enhanced *PPARγ2* expression in human colon adenocarcinoma cells. The activation of *PPARγ* can enhance *ABCA1* expression [97]. FaDOH treatment showed an upregulation of *ABCA1* in colon neoplastic rat tissue, suggesting a function for this transporter in the redistribution of lipids and the enhanced creation of LDs in cancer cells, which may result in endoplasmic reticulum (ER) stress and cancer cell death [97].
