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Review
. 2016 Dec;21(4):216-226.
doi: 10.15430/JCP.2016.21.4.216. Epub 2016 Dec 30.

Role of Apigenin in Cancer Prevention via the Induction of Apoptosis and Autophagy

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Free PMC article
Review

Role of Apigenin in Cancer Prevention via the Induction of Apoptosis and Autophagy

Bokyung Sung et al. J Cancer Prev. .
Free PMC article

Abstract

Apigenin (4',5,7-trihydroxyflavone) is a flavonoid commonly found in many fruits and vegetables such as parsley, chamomile, celery, and kumquats. In the last few decades, recognition of apigenin as a cancer chemopreventive agent has increased. Significant progress has been made in studying the chemopreventive aspects of apigenin both in vitro and in vivo. Several studies have demonstrated that the anticarcinogenic properties of apigenin occur through regulation of cellular response to oxidative stress and DNA damage, suppression of inflammation and angiogenesis, retardation of cell proliferation, and induction of autophagy and apoptosis. One of the most well-recognized mechanisms of apigenin is the capability to promote cell cycle arrest and induction of apoptosis through the p53-related pathway. A further role of apigenin in chemoprevention is the induction of autophagy in several human cancer cell lines. In this review, we discuss the details of apigenin, apoptosis, autophagy, and the role of apigenin in cancer chemoprevention via the induction of apoptosis and autophagy.

Keywords: Apigenin; Apoptosis; Autophagy; Chemoprevention.

Figures

Figure 1
Figure 1
Structure and natural sources of apigenin. Data from US Department of Agriculture (2011; https://www.ars.usda.gov/ARSUserFiles/80400525/Data/Flav/Flav_R03.pdf).
Figure 2
Figure 2
Signaling pathways and molecules involved in crosstalk between apoptosis and autophagy. Cellular stressors such as apigenin can start mitochondria outer membrane permeabilization and subsequent cytochrome c release and apoptosis induction, while nutrient deficiency or ER stress can cause autophagy activation. Under physiological conditions, apoptosis and autophagy keep each other inactive through mutual inhibition. A strong apoptotic stimulus (for example DNA damage, death-receptor stimulation, or cytokine deprivation) can drive a cell into apoptotic ‘type I’ cell death. If apoptosis is inhibited under such conditions (by caspase knockout or Bax/Bak knockout, [A]), autophagy can become activated and result in a delayed ‘type II’ cell death through degradation of most cytoplasmic cell components and organelles. Under these circumstances, the K.D. of autophagy related genes [B] reduces cell death. Autophagy can become activated through ER stress (for example, accumulation of misfolded proteins in the ER or intracellular calcium release from the ER) or nutrient deficiency. The cell then ensures survival by enhancing metabolic recycling through autophagy and adapting to the new nutrient conditions. K.D. of autophagy genes in such a situation leads to an increase in apoptotic ‘type I’ cell death [C]. The crosstalk between apoptosis and autophagy [D] is mediated via proteolytic processing of ATG5, the transcription factor p53, and the binding and subcellular localization of Bcl-2 family proteins with BH3 domains. Data from Jaeger and Wyss-Coray. ER, endoplasmic reticulum; K.D., knockdown.

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