More importantly, mitochondria are the potential target of Tan IIA. Mitochondria also control other apoptotic events, such as endoplasmic reticulum stress, the inflammation response, metabolic reprogramming, and autophagy. Increased mitochondrial apoptosis can induce extensive death of the cancer. On the other hand, mitochondrial damage such as mitochondrial oxidative stress and mitochondrial calcium overload can initiate a caspase-9-related mitochondrial apoptotic pathway. Cancer protein synthesis and DNA replication are also dependent on mitochondrial function. Cancer migration requires sufficient ATP to ensure cell mobility. Mitochondria homeostasis is closely associated with cancer progression and viability. These findings indicate that Tan IIA could be considered as an adjuvant effective drug to control the progression of human tumors.Īt the molecular levels, mitochondria are bioenergetic and biosynthetic organelles that produce enough energy to favor cell metabolism. Tan IIA effectively reduces the progression of ovarian cancer, gastric cancer, lung tumors, and bladder cancer. In addition, the antitumor property of Tan IIA has been well-documented. In chronic metabolic disorder, Tan IIA inhibits adipogenic differentiation, fatty liver disease and diabetic cardiomyopathy. In acute stress, Tan IIA alleviates the ischemia-reperfusion injury of the heart, liver, brain and kidneys. Several studies have reported that Tan IIA exhibits antioxidant, anti-inflammatory, and anticancer activities via multiple effects. Tanshinone IIA (Tan IIA), which is isolated from the roots of Salvia miltiorrhiza Bunge, is currently used to treat patients with cardiovascular disorders, stroke, diabetes and cancers. Accordingly, identifying effective approaches to control the development and progression of CRC is very important for patients with CRC. Despite the continuous advances and improvements in the screening and treatment of CRC, the death rate from CRC remains high. The standard treatment options for CRC include chemotherapy, radiotherapy, and surgery. The possible risk factors for CRC include age, a diet with lower fiber, a family history of CRC, obesity and smoking. It has been estimated that approximately 1 in 23 women in the United States will develop CRC during their lifetime. Furthermore, our findings demonstrate that Tan IIA is an effective drug to treat colorectal cancer by activating JNK-Mff-mitochondrial fission pathways.Ĭolorectal cancer (CRC) is the second leading cause of cancer death in women. ConclusionsĪltogether, our results identified mitochondrial fission as a new potential target to control cancer viability, mobility and proliferation. The blockade of the JNK-Mff axis inhibited Tan IIA-mediated mitochondrial fission and promoted the survival of SW837 cells. To this end, our results demonstrated that Tan IIA modulated mitochondrial fission via the JNK-Mff pathways. Furthermore, we confirmed that Tan IIA mediated mitochondrial damage by activating mitochondrial fission, and the inhibition of mitochondrial fission abrogated the proapoptotic effects of Tan IIA on SW837 cells. Functional investigation exhibited that Tan IIA treatment evoked mitochondrial injury, as witnessed by mitochondrial ROS overproduction, mitochondrial potential collapse, antioxidant factor downregulation, mitochondrial pro-apoptotic protein upregulation, and caspase-9-dependent apoptotic pathway activation. The results of our data illustrated that Tan IIA promoted SW837 cell death, impaired cell migration and mediated cancer proliferation arrest in a dose-dependent manner. In addition, the current study also investigated the therapeutic impact of Tanshinone IIA (Tan IIA), a type of anticancer adjuvant drug, on cancer mitochondrial homeostasis. The aim of our study was to determine the detailed role of mitochondrial fission in SW837 colorectal cancer cell viability, mobility and proliferation. Mitochondrial homeostasis has been increasingly viewed as a potential target of cancer therapy, and mitochondrial fission is a novel regulator of mitochondrial function and apoptosis.
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