Warburgia ugandensis Sprague (WU), a traditional medicinal plant native in Southern and Eastern Africa, is well known for its broad bioactivities, including antimicrobial, antifungal, and antimalarial effects. Apart from the above activities, WU is also used for the treatment of various cancers, but the underlying molecular mechanism remains unknown.    

Plant Chemical Biology Research Group from Wuhan Botanical Garden investigated the anti-non-small cell lung cancer (NSCLC) activities of WU against A549 (Non-small cell lung cancer) cells, and managed to reveal the potential molecular mechanisms.   

To investigate the anti-cancer potentials of WU, various WU extracts were tested for inhibitory cell growth activity on HeLa (cervical cancer), HepG2 (liver cancer), HT-29 (colorectal cancer) and A549 cells.    

The dimethyl carbonate extract of WU (WUD) exhibited the most potent inhibitory growth activity against the cancer cell, with a cell growth inhibition rate exceeding 80% against all four cancer cell lines. Moreover, its effects on cell viability, cell cycle progression, DNA damage, intracellular reactive oxygen species(ROS) and expression levels of G₀/ G₁- related proteins in A549 cells were further examined.    

In this work, WUD was firstly revealed to exhibit remarkable antiproliferative effects on A549 cells by improving the intracellular ROS level and by subsequently modulating the cell proliferation and G₀/ G₁ cell cycle progression of A549 cells. Furthermore, the FOXO3A (a negative regulator of SKP2) / SKP2 (S-phase kinase-associated protein 2) axis was implicated in the up-regulation of P27 (a negative regulator of the G1/S transition) upon treatment with WUD at a relatively high concentration (9 μg/mL). WUD also significantly induced γH2AX (a marker of double stranded DNA damage) expression and intracellular ROS generation of A549 cells.   

In conclusion, these findings imply the good therapeutic potential of WU for the NSCLC treatment. 

This work was jointly supported by the National Natural Science Foundation of China and the Youth Innovation Promotion Association of the Chinese Academy of Sciences. Prof. GUO Mingquan was the corresponding author and Dr. ZHANG Yongli was the first author. 

The research entitled “Stimulation of ROS Generation by Extract of Warburgia ugandensis Leading to G0/G1 Cell Cycle Arrest and Antiproliferation in A549 Cells” was published in Antioxidants.   

Stimulation of ROS Generation by Extract of Warburgia ugandensis Leading to G₀/G₁ Cell Cycle Arrest and Antiproliferation in A549 Cells (Image by ZHANG Yongli)