Triptonoterpene promotes the mitochondrial translocation of cofilin-1 to induce apoptosis in gastric cancer cells by regulating actin dynamics.

The pharmacological effects of the natural product triptonoterpene have been scarcely documented. In our preliminary investigations, we identified that triptonoterpene possesses the capacity to impede the invasion and migration of gastric cancer (GC) cells. We are committed to further exploring the potential extensive effects of triptonoterpene on GC and to clarifying its exact mechanism of action. This study was designed to examine the influence and underlying mechanisms of triptonoterpene on apoptosis in GC cells. Treatment with triptonoterpene effectively inhibited the proliferation of GC cells. We noted that triptonoterpene was capable of inducing apoptosis in GC cells, a process mediated through the mitochondrial pathway. Additionally, triptonoterpene was found to inhibit the polymerization of the actin cytoskeleton. The presence of triptonoterpene also disrupted the ROCK/LIMK/cofilin signaling pathway in GC cells. We hypothesize that triptonoterpene may trigger the mitochondrial apoptosis pathway by modulating the actin cytoskeleton. By employing Latrunculin A (LAT-A, an actin filament disruptor) and BMS-5 (a LIMK inhibitor) to manipulate actin dynamics, we observed that both LAT-A and BMS-5 enhanced triptonoterpene-induced apoptosis and the accumulation of reactive oxygen species (ROS), and intensified the decline in mitochondrial membrane potential (MMP). Intriguingly, we discovered that GC cells treated with triptonoterpene exhibited mitochondrial fragmentation and colocalization of cofilin-1 with mitochondria. Western blot analysis further revealed that triptonoterpene facilitated the translocation of cofilin-1 from the cytoplasm to the mitochondria. Finally, the results of our in vivo experiments indicated that triptonoterpene significantly inhibited the proliferation of xenograft tumors and induced tumor cell apoptosis. This study provides experimental evidence for the development of triptonoterpene and explores new pathways for cancer treatment.