Reactive oxygen species: Key players in the anticancer effects of apigenin?

Abstract

Reactive oxygen species (ROS) exhibit a double-edged sword in cancer-hence their modulation has been an attractive strategy in cancer prevention and therapy. The abundance of scientific information on the pro-oxidant effects of apigenin in cancer cells suggests the crucial role of ROS in its mechanisms of action. Although apigenin is known to enhance the cellular ROS levels to cytotoxic degrees in cancer cells in vitro, it remains to be determined if these pro-oxidant effects prevail or are relevant in experimental tumor models and clinical trials. Here, we critically examine the prooxidant and antioxidant effects of apigenin in cancer to provide insightful perspectives on the association between its ROS-modulating action and anticancer potential.We also discussed these effects in a cell/tissue type-specific context to highlight the factors influencing the switch between antioxidant and pro-oxidant effects. Finally, we raised some questions that need addressing for the potential translation of these studies into clinical applications. Further research into this duality in oxidant actions of apigenin, especially in vivo, may enable better exploitation of its anticancer potential.Practical application: Apigenin is a naturally occurring compound found in chamomile flowers, parsley, celery, peppermint, and citrus fruits. Many human trials of dietary interventions with apigenin-containing herbs and flavonoid mixture on oxidative stress markers, for instance, point to their antioxidant effects and health benefits in many diseases. Preclinical studies suggest that apigenin alone or its combination with chemotherapeutics has a strong anti-neoplastic effect and can induce ROS-mediated cytotoxicity at concentrations in the micromolar (μM) range, which may not be feasible with dietary interventions. Enhancing the in vivo pharmacokinetic properties of apigenin may be indispensable for its potential cancer-specific pro-oxidant therapy and may provide relevant information for clinical studies of apigenin either as a single agent or an adjuvant to chemotherapeutics.

Role of Reactive Oxygen Species in Aging and Age-Related Diseases: A Review

“…Although some cell culture studies and animal studies suggest that antioxidants can be used to fight oxidative damage hence decelerating the aging process, it is imperative to test those hypotheses in a clinical trial. 331 A recent study of 2570 women aged between 18 and 79 years found that Vitamin E is effective to maintain and grow higher skeletal muscle mass, which can eventually prevent sarcopenia. 332 Another randomized clinical trial conducted on 334 human beings suggested that Mediterranean diets containing olive oil and nuts can slow down age-related cognitive decline and decelerate the risk of developing dementia.…”

“…To tackle the intracellular ROS homeostasis shift, cells use an array of antioxidant systems that are supported by certain cofactors and an exogenous supply of antioxidants. Although some cell culture studies and animal studies suggest that antioxidants can be used to fight oxidative damage hence decelerating the aging process, it is imperative to test those hypotheses in a clinical trial . A recent study of 2570 women aged between 18 and 79 years found that Vitamin E is effective to maintain and grow higher skeletal muscle mass, which can eventually prevent sarcopenia .…”

Ethanolic extract of Origanum syriacum L. leaves exhibits potent anti-breast cancer potential and robust antioxidant properties

“…Reactive oxygen species function like a double-edged sword in cancer progression, depending on their concentration in the cell and the stage of cancer. ROS have been reported to either enhance tumorigenesis and promote tumor progression by causing DNA damage and inducing pro-oncogenic pathways, or to induce cell death and apoptosis of cancer cells ( Shaito et al, 2020 ; Oyenihi et al, 2022 ; Oyenihi et al, 2022 ). To investigate whether OSEE exerts anti-proliferative effects on MDA-MB-231 cells through ROS generation, MDA-MB-231 cells were first pre-treated with NAC to dampen ROS generation, followed by treatment with OSEE at various concentrations.…”

“…Reactive oxygen species function like a double-edged sword in cancer progression, depending on their concentration in the cell and the stage of cancer. ROS have been reported to either enhance tumorigenesis and promote tumor progression by causing DNA damage and inducing pro-oncogenic pathways, or to induce cell death and apoptosis of cancer cells (Shaito et al, 2020;Oyenihi et al, 3C). Figure 3C also shows that treatment with NAC augmented the inhibition of proliferation of MDA-MB-231 cells treated with lower concentrations of OSEE (50 and 100 μg/ml).…”

Deciphering the modulatory role of apigenin targeting oncogenic pathways in human cancers

“…Apigenin inhibits the phosphorylation of ERK1/2 and FAK, which in turn encourages poor integrin synthesis and death. On the other hand, apigenin has also been observed to increase ERK expression in a few different tumor types (Cai et al, 2022; Che et al, 2020; Erdogan et al, 2020; Lee et al, 2019; Oyenihi et al, 2022). In conclusion, these findings support the notion that apigenin can induce apoptosis by deregulating MAPK/ERK signaling pathway in cancer cells.…”