Pancreatic adenocarcinoma (PAAD) is one of the deadliest forms of cancer, with a five-year survival rate lower than 5%. The chemotherapy drug gemcitabine (GEM) is typically used to treat PAAD, but cancer cells can sometimes exhibit GEM resistance, making treatment options severely limited. Researchers from the Chinese Academy of Medical Sciences and Peking Union Medical College have now identified anti-cancer properties in a natural compound produced by certain types of fungus, which could inhibit growth in PAAD tumors, including those resistant to GEM.
Secoemestrin C (Sec C) is produced by Emericella fungi and has low toxicity compared to many cancer drugs. The researchers investigated the anticancer potential of Sec C through several methods, including cell growth inhibition assays, RNA-seq to evaluate protein expression changes with Sec C exposure, in vivo experiments tracking tumor growth in mice, electron microscopy examinations of treated and untreated tumor cells, and microcapillary liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses for a better understanding of how Sec C interacts with and alters PAAD cell chemical activity.
These tests indicated that endoplasmic reticulum (ER) proteins in PAAD cells exposed to Sec C exhibited stress and misfolding, reducing the ability for these cells to grow and survive. The LC-MS/MS analysis showed that PAAD cells treated with Sec C contained adducts of Sec C and cysteine, suggesting that the ability of Sec C to bind with ER cysteines prevents those cysteines from forming the disulfide bonds necessary for the correct folding of ER proteins. This folding disruption appears to induce ER stress and lead to cancer cell death. The study was published in Acta Pharmaceutica Sinica B.
The research reported that overall, Sec C provided a rapid growth-inhibiting effect of 80% PAAD cell death after six hours, indicating it could be beneficial for patients requiring rapid tumor shrinkage prior to surgery. Additionally, Sec C was able to inhibit growth in both GEM-sensitive and GEM-resistant cancer cells, making it a promising candidate for future anticancer therapies.