Aberrant upregulation of mitochondrial biogenesis is observed in breast cancer and holds potential therapeutic option. In our work, we showed that inhibition of mitochondrial function by anisomycin is effective against triple-negative breast cancer (TNBC). Anisomycin inhibits growth and induces caspase-dependent apoptosis in a panel of TNBC cell lines. Of note, anisomycin at a tolerable dose remarkably suppresses growth of TNBC in mice. In addition, anisomycin effectively targets breast cancer angiogenesis through inhibiting capillary network formation, migration, proliferation, and survival. Mechanistic studies show that although anisomycin activates p38 and JNK, their activations are not required for anisomycin's action. In contrast, anisomycin inhibits mitochondrial respiration, and decreases mitochondrial membrane potential and adenosine triphosphate (ATP) level. The inhibitory effect of anisomycin is significantly reversed in mitochondria respiration-deficient ρ0 cells. As a consequence, anisomycin activates AMPK and inhibits mammalian target-of-rapamycin signaling pathways. Our work demonstrated that anisomycin is a useful addition to the treatment armamentarium for TNBC.

Introduction Carcinosarcoma (CS) is a rare malignant tumor. Little is known about the epidemiological feature of the disease in literature. Our aim is to offer the largest and latest analysis of the incidence, mortality, and survival of CS. Methods Data of CS from the Surveillance, Epidemiology, and End Results (SEER) database (SEER-9 incidence database and SEER-9 incidence-based mortality database) were adopted. Incidence, mortality, and survival analyses were performed by SEER*Stat software. We used annual percentage change (APC) to evaluate the trends in incidence and mortality. Results Incidence rate increased from 0.36/100,000 to 0.83/100,000 with an APC of 3.4% from 1975 to 2018. Mortality rate followed a similar pattern of increase at an APC of 3.2% from 0.07/100,000 in 1975 to 0.54/100,000 in 2018. Most CS occurred in the female genital system and the 5-year survival rate of all patients was 34.9%. Conclusion CS is an aggressive tumor with increasing incidence and mortality trends. This tumor, especially CS in the female genital system, is no longer considered to be a rare tumor in the near future. This research will broad our knowledge for CS as well as provide insight for clinicians.