Fructose‐1,6‐bisphosphate induces generation of reactive oxygen species and activation of p53‐dependent cell death in human endometrial cancer cells

Abstract

Fructose‐1,6‐bisphosphate (F1,6BP), an intermediate of the glycolytic pathway, has been found to play a promising anticancer effect; nevertheless, the mechanisms involved remain poorly understood. The present study aimed to evaluate the effect and mechanisms of F1,6BP in a human endometrial cancer cell line (Ishikawa). F1,6BP showed an antiproliferative and non‐cytotoxic effect on endometrial cancer cells. These effects are related to the increase in reactive oxygen species (ROS) levels and mitochondrial membrane potential (ΔΨm). These harmful stimuli trigger the upregulation of the expression of pro‐apoptotic genes (p53 and Bax), leading to the reduction of cell proliferation through inducing programmed cell death by apoptosis. Furthermore, F1,6BP‐treated cells had the formation of autophagosomes induced, as well as a decrease in their proliferative capacity after withdrawing the treatment. Our results demonstrate that F1,6BP acts as an anticancer agent through the generation of mitochondrial instability, loss of cell function, and p53‐dependent cell death. Thus, F1,6BP proves to be a potential molecule for use in the treatment against endometrial cancer.

Nuclear Fructose‐1,6‐Bisphosphate Inhibits Tumor Growth and Sensitizes Chemotherapy by Targeting HMGB1

“…However, after knocking down ALODA, the above effect of F1,6P treatment has not been negated (Figure S1g, Supporting Information), suggesting that the specific effect of F1,6P is largely independent of its role in glycolysis. In line, this effect of F1,6P has also been detected in other cancer cells, [24,25] and reactive oxygen species (ROS) induction has been suggested to underlie it. [25] However, an inhibitory effect of exogenous F1,6P on ROS level has also been reported [8,9] as well as detected in our study (Figure S1h, Supporting Information), suggesting that ROS induction is not the common mechanism in various cancer cells.…”

“…In line, this effect of F1,6P has also been detected in other cancer cells, [24,25] and reactive oxygen species (ROS) induction has been suggested to underlie it. [25] However, an inhibitory effect of exogenous F1,6P on ROS level has also been reported [8,9] as well as detected in our study (Figure S1h, Supporting Information), suggesting that ROS induction is not the common mechanism in various cancer cells. In any case, our findings here indicate that F1,6P treatment broadly impairs viability of different cancer cells mainly through nuclear-accumulated F1,6P.…”

Diagnostic accuracy of shear wave elastography for endometrial cancer: A meta-analysis

“…Most uterine cancers are referred to as EC, which originates from the epithelial lining of the uterine cavity. [ 24 ] Early diagnosis and treatment can effectively improve patient prognosis, which has important clinical significance. Transvaginal color Doppler ultrasonography is a simple operation with intuitive, noninvasive, and other advantages, and has become a common method for the clinical diagnosis of EC.…”

Glucose metabolic reprogramming and its therapeutic potential in obesity-associated endometrial cancer

“…ALDH-dependent GLUT1 upregulation contributes to the activation of glycolysis and survival of cancer stem cells; the synergistic role of inhibition of ALDH or GLUT1 combined with taxane suppresses the tumorigenesis, which provides a new prospect for EC treatment [ 86 ]. Fructose-1,6-bisphosphate (F-1,6-BP), one metabolic intermediate of glycolytic pathway, promotes the generation of ROS and P53-dependent death in EC cells [ 87 ]. Genes associated with the regulation of glycolysis may affect biological behavior of EC cells.…”