Gratiola officinalis Alcoholic Extract Targets Warburg Effect, Apoptosis and Cell Cycle Progression in Colorectal Cancer Cell Lines

Colorectal cancer (CRC) is the second deadliest cancer in the Western world. Increased body weight, a diet rich in red meat and alcohol, as well as a sedentary lifestyle, are all involved in sporadic CRC pathogenesis. Since current CRC therapies show several side effects, there is a need to find new and more effective therapeutic approaches, allowing conventional drug dosages and toxicity to be reduced. <i>Gratiola officinalis</i> alcoholic extract was characterized by LC-MS and its effect investigated on a healthy colon mucosa cell line and on different colorectal cancer cell lines. Cell viability, apoptosis and cell cycle progression were evaluated through flow cytometry; energy production and glycolysis were investigated using Seahorse technology, while cancer markers were analyzed through Western blotting. The untargeted metabolomics analysis of <i>G. officinalis</i> alcoholic extract revealed glycosides of different polyphenols and glycosides of cucurbitane-type triterpenes. This extract showed a stronger impact on CRC cell line viability compared to healthy colon cells. In the E705 CRC cell line, it induced cell apoptosis and caused the downregulation of glycolysis, inhibiting cell proliferation. On the other hand, SW480 CRC cells treated with <i>G. officinalis</i> extract showed G₂/M cell cycle arrest. This work shows that <i>G. officinalis</i> extract can reduce glycolysis and promote cell cycle arrest in CRC cells, suggesting that <i>G. officinalis</i> could represent a novel player in the prevention and treatment of CRC.