Autophagy activation by dietary piceatannol enhances the efficacy of immunogenic chemotherapy

Wang，Shuang1; Wang，Guangsuo2; Wu，Weiqing3; Xu，Zhenglei4; Yang，Jing1; Cao，Min1; Wang，Qi5; Wang，Jigang1,6; Yang，Chuanbin1; Zhang，Wei1,7

2022

10.3389/fimmu.2022.968686

Frontiers in immunology   Impact Factor & Quartile

1664-3224

Immunogenic cell death (ICD) promotes the immune antitumor response via releasing damage-associated molecular patterns (DAMPs) from dying tumor cells. The induction of autophagy improves the efficacy of multiple immunogenic chemotherapies. Here, we show that piceatannol, a dietary phenolic compound that is widely distributed in multiple fruits and vegetables such as grapes, blueberries, and mushrooms, induces autophagy and enhances oxaliplatin (OXA)-induced anticancer immune response. Specifically, piceatannol enhanced OXA-induced release of DAMPs, several key hallmarks of ICD including ATP release, cell surface exposure of calreticulin, and high-mobility group box 1 (HMGB1) release. Mechanistically, piceatannol promoted autophagy via activating TFEB/TFE3, two key transcription factors of the autophagy-lysosome pathway, and inhibiting autophagy attenuated piceatannol plus OXA-induced ATP release. Furthermore, piceatannol induced endoplasmic reticulum stress, which is critical for its role in enhancing OXA-induced cell surface exposure of calreticulin, another key hallmark of ICD. Consistently, the combination of piceatannol with OXA promoted the anticancer effects in immunocompetent mice. Taken together, our results indicate the importance and great potential of dietary piceatannol in cancer immunotherapy. Therefore, piceatannol may be used as an ICD enhancer that improves the efficacy of chemotherapeutics such as OXA in cancer treatment with minimized toxicity.

autophagy endoplasmic reticulum (ER) stress immunogenic cell death (ICD) piceatannol transcription factor EB (TFEB)

English

First

2-s2.0-85136053534

Scopus

1.Department of Geriatrics,Shenzhen People's Hospital,Second Clinical Medical College,Jinan University,First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,China
2.Department of Thoracic Surgery,Shenzhen People's Hospital,Second Clinical Medical College,Jinan University,First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,China
3.Department of Health Management,Shenzhen People's Hospital,Second Clinical Medical College,Jinan University,First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,China
4.Department of Gastroenterology,Shenzhen People's Hospital,Second Clinical Medical College,Jinan University,First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,China
5.Shenzhen People's Hospital,Second Clinical Medical College,Jinan University,First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,China
6.Artemisinin Research Center,Institute of Chinese Materia Medica,Chinese Academy of Chinese Medical Sciences,China
7.Jinan University,Guangzhou,Integrated Chinese and Western Medicine Postdoctoral Research Station,China

Wang，Shuang,Wang，Guangsuo,Wu，Weiqing,et al. Autophagy activation by dietary piceatannol enhances the efficacy of immunogenic chemotherapy[J]. Frontiers in immunology,2022,13.

Wang，Shuang.,Wang，Guangsuo.,Wu，Weiqing.,Xu，Zhenglei.,Yang，Jing.,...&Zhang，Wei.(2022).Autophagy activation by dietary piceatannol enhances the efficacy of immunogenic chemotherapy.Frontiers in immunology,13.

Wang，Shuang,et al."Autophagy activation by dietary piceatannol enhances the efficacy of immunogenic chemotherapy".Frontiers in immunology 13(2022).