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Review
. 2025 Mar 13;14(3):339.
doi: 10.3390/antiox14030339.

The Interplay Between Autophagy and Apoptosis in the Mechanisms of Action of Stilbenes in Cancer Cells

Kamila Siedlecka-Kroplewska  1 , Zbigniew Kmiec  2 , Michal Aleksander Zmijewski  1
Affiliations
Review

The Interplay Between Autophagy and Apoptosis in the Mechanisms of Action of Stilbenes in Cancer Cells

Kamila Siedlecka-Kroplewska et al. Antioxidants (Basel). .

Abstract

Plant-based stilbenes are low-molecular-weight polyphenolic compounds that exhibit anti-oxidant, anti-microbial, anti-fungal, anti-inflammatory, anti-diabetic, cardioprotective, neuroprotective, and anti-cancer activities. They are phytoalexins produced in diverse plant species in response to stress, such as fungal and bacterial infections or excessive UV irradiation. Plant-derived dietary products containing stilbenes are common components of the human diet. Stilbenes appear to be promising chemopreventive and chemotherapeutic agents. Accumulating evidence indicates that stilbenes are able to trigger both apoptotic and autophagic molecular pathways in many human cancer cell lines. Of note, the molecular crosstalk between autophagy and apoptosis under cellular stress conditions determines the cell fate. The autophagy and apoptosis relationship is complex and depends on the cellular context, e.g., cell type and cellular stress level. Apoptosis is a type of regulated cell death, whereas autophagy may act as a pro-survival or pro-death mechanism depending on the context. The interplay between autophagy and apoptosis may have an important impact on chemotherapy efficiency. This review focuses on the in vitro effects of stilbenes in different human cancer cell lines concerning the interplay between autophagy and apoptosis.

Keywords: apoptosis; autophagy; cancer cells; cell death; piceatannol; polyphenols; pterostilbene; resveratrol; stilbenes; stilbenoids.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Classification of polyphenols (created in BioRender.com).
Figure 2
Figure 2
The chemical structure of stilbene.
Figure 3
Figure 3
Chemical structures of selected stilbenes. RES, resveratrol; PIC, piceatannol; OXYRES, oxyresveratrol; PIN, pinosylvin; PTER, pterostilbene; RHAP, rhapontigenin; GNE, gnetol; ISORHAP, isorhapontigenin; CA-4, combrestatin A-4; DEOXYRHAP, deoxyrhapontigenin.
Figure 4
Figure 4
Biological activities of stilbenes (created in BioRender.com).
Figure 5
Figure 5
Overview of macroautophagy. EE—early endosome, MVB/LE—multivesicular body/late endosome; LY—lysosome. Created in BioRender.com.
Figure 6
Figure 6
Overview of apoptosis. DISC, death-inducing signaling complex; MOMP, mitochondrial outer membrane permeabilization. Created in BioRender.com.
Figure 7
Figure 7
The interplay of autophagy and apoptosis. Created in BioRender.com.
See this image and copyright information in PMC

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