Abstract
Echinacoside is a natural compound with potent reactive oxygen species (ROS)-scavenging and anti-oxidative bioactivities, which protect cells from oxidative damages. As cancer cells are often under intense oxidative stress, we therefore tested if Echinacoside treatment would promote cancer development. Surprisingly, we found that Echinacoside significantly inhibited the growth and proliferation of a panel of cancer cell lines. Treatment of the human SW480 cancer cells with Echinacoside resulted in marked apoptosis and cell cycle arrest, together with a significant increase in active caspase 3 and cleaved PARP, and upregulation of the G1/S-CDK blocker CDKN1B (p21). Interestingly, immunocytochemistry examination of drug-treated cancer cells revealed that Echinacoside caused a significant increase of intracellular oxidized guanine, 8-oxoG, and dramatic upregulation of the double-strand DNA break (DSB)-binding protein 53BP1, suggesting that Echinacoside induced cell cycle arrest and apoptosis in SW480 cancer cells via induction of oxidative DNA damages. These results establish Echinacoside as a novel chemical scaffold for development of anticancer drugs.
Highlights
Echinacoside is a natural compound derived from the medicinal plant species of the genus of Cistanche [1,2] as well as Echinacea [3,4]
Treatment of SW480 cells with different doses of Echinacoside showed that Echinacoside dose-dependently inhibited the growth of SW480 cells (Figure 1C)
The results showed that 24 h treatment by 60 and 80 μM Echinacoside clearly increased the level of active caspase 3 and cleaved PARP proteins in SW480 cells (Figure 4A,B), indicating that Echinacoside activated caspase-dependent apoptosis
Summary
Echinacoside is a natural compound derived from the medicinal plant species of the genus of Cistanche [1,2] as well as Echinacea [3,4]. Extracts from the stem of different parasitic Cistanche plants have been used as a tonic in China for thousands of years [2], and extracts of Echinacea is one of the most popular herbal supplements in the US and Europe [3], being used widely to treat common cold and infections [4]. Cancer cells generate much higher ROS and are highly dependent on efficient prevention of ROS-associated DNA damages for survival [19] In this regard, highly proliferating cancer cells may benefit more from the anti-oxidative and ROS-scavenging activities of antioxidants than normal cells. Given its many other health beneficial bioactivities, these results establish Echinacoside as a novel chemical scaffold for the development of anticancer drugs
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