Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells

Abstract

Chemotherapy continues to play an essential role in the management of many cancers including colon cancer, the third leading cause of death due to cancer in the United States. Many naturally occurring plant compounds have been demonstrated to possess anti-cancer cell activity and have the potential to supplement existing chemotherapy strategies. The plant metabolite andrographolide induces cell death in cancer cells and apoptosis is dependent upon the induction of endoplasmic reticulum stress (ER stress) leading to the unfolded protein response (UPR). The goal of the present study was to determine the mechanism by which andrographolide induces ER stress and to further evaluate its role in promoting cell death pathways. The T84 and COLO 205 cancer cell lines were used to demonstrate that andrographolide induces increased ROS levels, corresponding anti-oxidant response molecules, and reduced mitochondrial membrane potential. No increases in ROS levels were detected in control colon fibroblast cells. Andrographolide-induced cell death, UPR signaling, and CHOP, Bax, and caspase 3 apoptosis elements were all inhibited in the presence of the ROS scavenger NAC. Additionally, andrographolide-induced suppression of cyclins B1 and D1 were also reversed in the presence of NAC. Finally, Akt phosphorylation and phospho-mTOR levels that are normally suppressed by andrographolide were also expressed at normal levels in the absence of ROS. These data demonstrate that andrographolide induces ER stress leading to apoptosis through the induction of ROS and that elevated ROS also play an important role in down-regulating cell cycle progression and cell survival pathways as well.

Upregulation of RASSF1A in Colon Cancer by Suppression of Angiogenesis Signaling and Akt Activation

“…2) However, in the subsequent study we found, AGP induces ER stress leading to apoptosis through the induction of Reactive Oxygen Species (ROS) and play an important role in down-regulating cell cycle progression and cell survival pathways as well. 3) In addition, we have also demonstrated that AGP downregulates the Akt/mTOR survival pathway in this model [17]. In our study, we also observed inactivation of NF-kβ in andrographolide treated colon cancer cells (data not shown) similar to the previously reported [25].…”

Tannic acid inhibits lipid metabolism and induce ROS in prostate cancer cells

“…Intracellular abnormalities related to the function of ER, such as activation of unfolded protein response (UPR), trigger ER stress 13 . Prevalence of ER stress is also associated with the oxidative stress in cancer cells 14 . Oxidative stress causes cellular damage by ROS production in cells with compromised antioxidant resistance mechanism.…”

Taurine alleviates endoplasmic reticulum stress in the chondrocytes from patients with osteoarthritis

“…It is known that an increase in Reactive oxygen species (ROS), including hydrogen peroxide (H 2 O 2 ), superoxide (O − 2 ) and hydroxyl radical (•OH), impairs intracellular calcium homeostasis and subsequently results in ER stress [33]. Pan et al (2010) found that H 2 O 2 increased oxidative stress and up-regulated the expressions of GRP-78 and GADD153 in rat phenocromocytoma Figure 5.…”

“…PC12 cells [34]. Banerjee et al (2017) reported that that andrographolide treatment induced ROS production in colon cancer cells and that elevated ROS caused ER stress, which subsequently inducing cell apoptosis process [33]. In order to examine whether taurine exerted cytoprotective effects against H 2 O 2 induced oxidative stress related to ER stress, Western blot analysis was employed to assay the protein levels of Collagen II and three ER stress markers.…”