The combination of piceatannol and mTOR inhibitor proves to be an attractive therapeutic strategy for gastric cancer

The combination of piceatannol and mTOR inhibitor proves to be an attractive therapeutic strategy for gastric cancer

This study is led by Dr. Longtao Huangfu and Dr. Xiaoyang Wang (Peking University Cancer Hospital & Institute). A diet containing fresh fruits and vegetables can reduce the prevalence of cancers, including GC (Eusebi et al., 2020; Liu et al., 2021). In addition, clinical studies have found that certain biologically active food molecules can inhibit multiple steps in the signaling pathways associated with carcinogens (Arai and Nakajima, 2020).

Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene), an analogue of resveratrol, is a naturally occurring polyphenolic compound found in approximately 70 plant sources, including passion fruit, rhubarb, and legumes (Banik et al., 2020; Seyed et al., 2016). This compound was first described as a bioactive antitumor molecule in 2003 (Larrosa et al., 2004). Subsequent reports showed that piceatannol affects various signaling pathways and exerts antitumor effects on various cancers, including colorectal cancer, lung cancer, and lymphoma (Cao et al., 2020; Nayyab et al., 2020). Therefore, piceatannol may be an effective drug for GC treatment. In fact, the study of the effects caused by its comparable bioactive properties has become a focus in relevant research areas.

The research team determined that piceatannol is a potential targeting agonist of Beclin-1 to evaluate its effectiveness as an antitumor agent against GC. For this purpose, this group uses several human GC cell lines as well as a murine xenograft model. The results show that piceatannol inhibits cell proliferation and enhances autophagic activity in GC cells. Furthermore, piceatannol was found to directly target Beclin-1 by inhibiting its phosphorylation at Ser-295, a canonical site for the negative regulation of autophagic activity, thereby increasing autophagic flux through the Beclin-1-dependent pathway in GC cells. This team analyzed the synergistic antitumor activity of compounds known to regulate and interact with the Beclin-1 network. Overall, this research suggests that piceatannol in combination with the mTOR inhibitor everolimus exhibits strong synergistic effects across a broad range of dose-responses, proving to be an attractive therapeutic strategy for GC.

Source:

Science China Press

Reference:

Huangfu, L., et al. (2022) Piceatannol enhances the activity of Beclin-1 to suppress tumor progression and its combination therapy strategy with everolimus in gastric cancer. Science China Life Sciences. doi.org/10.1007/s11427-022-2185-9.

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