Ellagic acid (EA)—a natural polyphenol compound found in red wine—may inhibit the proliferation of lung cancer cells by inducing autophagy, according to a recent study published in the Journal of Cellular and Molecular Medicine. Further, researchers found that EA also has anti-lung cancer effects both in vitro and in vivo.
Previous research has shown that resveratrol, another component of red wine, offers strong protection against metabolic, cardiovascular, and neurodegenerative diseases, as well as chemopreventive and antiproliferative effects in some cancers. But EA—found in grapes, raspberries, strawberries, cranberries, pomegranates, black berries, and nuts—exists in even higher concentrations in red wine than resveratrol. Previous studies have shown that EA has potent antioxidant and preventive effects in several types of cancer. However, EA’s effects on lung cancer, specifically, are unknown.
To that end, researchers led by Jing Duan, Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China, tested 11 components of red wine to assess their possible anti-lung cancer activity, including resveratrol, ferulic acid, epicatechin, EA, rutin, chlorogenic acid, coumalic acid, vanillic acid, syringic acid, morin, and phloridzin.
To determine which compounds had anticancer activities, they performed MTT assays. Nine of the 11 compounds demonstrated low rates of proliferation inhibition of less than 15%, but both EA and resveratrol both had significant inhibition rates—between approximately 50% to 80% after 72 hours. EA inhibited the proliferation of lung cancer cells almost as well as resveratrol.
Additional effects of EA also included:
- Increased expression of LC3-II, an autophagosomal marker;
- Inactivation of rapamycin signaling pathway targets;
- Elevated cell death associated with autophagy through downregulation of cancerous inhibitor of protein phosphatase 2A (CIP2A); and
- Autophagy of lung cancer cells.
“These results indicate that EA is a CIP2A inhibitor and an autophagy inducer in lung cancer,” wrote Duan and coauthors.
CIP2A is notorious for facilitating the growth and aggressiveness of cancer cells.
“CIP2A or KIAA1524/p9022, is an oncoprotein [that] promotes tumorigenesis through facilitation of the biological functions of cancer drivers (c-Myc, Akt, etc.) and inhibition of PP2A activity,” they explained. “CIP2A controls autophagy and cell growth through mTORC1 activation, synergizes with RAS, and crosstalks with Wnt/β-catenin signal pathway to promote cell proliferation and cancer progression. It also mediates interleukin 10-induced tumor aggressiveness.”
In a nod to traditional Chinese medicine, Duan and colleagues also tested a combination of EA and a medicinal herb, celastrol—a pentacyclic triterpenoid isolated from the root extracts of Tripterygium wilfordii (Thunder god vine) and Celastrus regelii that has been studied for its effects on obesity as a leptin sensitizer. The combination brought about increased inhibitory effects on lung cancer cells both in vitro and in vivo through enhanced autophagy and down regulated CIP2A.
Thus, they concluded: “These findings indicate that EA may be a promising chemotherapeutic agent for lung cancer, and that the combination of EA and celastrol may have applicability for the treatment of this disease.”
This study was supported by the Open Foundation of Beijing Advanced Innovation Center for Food Nutrition and Human Health, National Natural Science Funds for Distinguished Young Scholars, the National Key Research and Development Program of China, and the National Natural Science Foundation of China.