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Prior research has demonstrated how the endoplasmic reticulum (ER) functions as a multifunctional organelle and as a well-orchestrated protein-folding unit. It consists of sensors which detect stress-induced unfolded/misfolded proteins and it is the place where protein folding is catalyzed with chaperones. During this folding process, an immaculate disulfide bond formation requires an oxidized environment provided by the ER. Protein folding and the generation of reactive oxygen species (ROS) as a protein oxidative byproduct in ER are crosslinked. An ER stress-induced response also mediates the expression of the apoptosis-associated gene C/EBP-homologous protein (CHOP) and death receptor 5 (DR5). ER stress induces the upregulation of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor and opening new horizons for therapeutic research. These findings can be used to maximize TRAIL-induced apoptosis in xenografted mice. This review summarizes the current understanding of the interplay between ER stress and ROS. We also discuss how damage-associated molecular patterns (DAMPs) function as modulators of immunogenic cell death and how natural products and drugs have shown potential in regulating ER stress and ROS in different cancer cell lines. Drugs as inducers and inhibitors of ROS modulation may respectively exert inducible and inhibitory effects on ER stress and unfolded protein response (UPR). Reconceptualization of the molecular crosstalk among ROS modulating effectors, ER stress, and DAMPs will lead to advances in anticancer therapy.

It is becoming more understandable that an existing challenge for translational research is the development of pharmaceuticals that appropriately target reactive oxygen species (ROS)-mediated molecular networks in cancer cells. In line with this approach, there is an overwhelmingly increasing list of many non-marine drugs and marine drugs reported to be involved in inhibiting and suppressing cancer progression through ROS-mediated cell death. In this review, we describe the strategy of oxidative stress-based therapy and connect the ROS modulating effect to the regulation of apoptosis and autophagy. Finally, we focus on exploring the function and mechanism of cancer therapy by the autophagy modulators including inhibitors and inducers from non-marine drugs and marine drugs.

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Many red algae-derived natural products are known to have anticancer effects. The biological functions of the red alga Solieria robusta from the Karachi coast (Pakistan) remain unclear. Here, we prepared a methanolic extracts of S. robusta (MESR) to examine its possible anti-oral cancer effects and the corresponding mechanism of action. Cell viability of MESR-incubated oral cancer Ca9-22 cells was dose-responsively decreased (p < 0.001). According to a propidium iodide (PI)-based assay the cell cycle distribution was dramatically changed, especially for subG1 accumulation. Annexin V/PI assay of apoptosis using flow cytometry also showed that MESR-incubated Ca9-22 cells were dose-responsively increased (p < 0.001). For evaluation of oxidative stress in MESR-incubated Ca9-22 cells, we found that reactive oxygen species (ROS) were overexpressed dose-and time-responsively and mitochondrial depolarization was also increased (p < 0.001). Taken together, MESR showed inhibitory effects on oral cancer proliferation coupled with apoptosis and oxidative stress.