Colorectal cancer (CRC) is one of the most common
digestive system cancer in the world. Its incidence and mortality are increasing annually. Presently, CRC lacks long-term effective treatment methods and drugs. Therefore, finding new treatment methods and drugs is of great significance for CRC treatment. Compounds derived from natural plants have been widely used in
tumor research and treatment because of their good antitumor activity these years. This study found that
nodosin, a
diterpenoid extracted from the medicinal plant Rabdosia serra (Maxim.) Hara, inhibited the growth of CRC cells SW480, HT-29 and LoVo in a dose- and time-dependent manner, with inhibitory concentrations (IC50) of 7.4, 7.7, and 6.6 μM respectively. We selected highly metastatic and poorly differentiated SW480 cells for further studies. We found that
nodosin could inhibit cell proliferation by inhibiting
DNA synthesis and induce cell death by inducing oxidative stress, apoptosis and autophagy in cells. Through in vitro assays combined with transcriptomic analysis, it was found that
nodosin could downregulate tribbles pseudokinase 3 and upregulate oxidative stress-induced
growth inhibitor 1 to induce oxidative stress in cells;
nodosin-induced
reactive oxygen species were able to upregulate the expression of
heme oxygenase 1 to induce apoptosis and the expression of
cathepsin L. and light chain-3 to induce autophagy. In vivo, we found that
nodosin inhibited
tumor growth and induced cells to undergo apoptosis and autophagy without significant toxic effects. In conclusion, our findings suggest that
nodosin exerts anti-CRC effects mainly through its ability to induce apoptosis and autophagy in vitro and in vivo. Therefore, our study contributes to the development of
nodosin-based potential CRC therapeutic drugs.