Effect of mesenchymal stem cells on cytochrome-c release and inflammation in colon cancer induced by 1,2-dimethylhydrazine in Wistar albino rats

Abstract

Colon cancer is one of the most common causes of death by cancer worldwide. Stem cells have immunosuppressive properties that promote tumor targeting and circumvent obstacles currently in gene therapy. Bone marrow stem cells are believed to have anticancer potential. The transplantation of mesenchymal stem cells (MSCs), a type of bone marrow stem cells, has been considered a potential therapy for patients with solid tumors due to their capability to enhance the immune response; MSC transplantation has received renewed interest in recent years. This study aimed to evaluate the antiapoptotic effects of the MSCs on 1,2-dimethylhydrazine (DMH)-induced inflammation in the rat model of colorectal cancer. The rats were randomly allocated into four groups: control, treated with MSCs, induced by DMH, and induced by DMH and treated with MSCs. The MSCs were intra-rectally injected, and DMH was subcutaneously injected at 20 mg/kg body weight once a week for 15 weeks. The administration of MSCs into rats starting from day 0 of the DMH injection was found to enhance the histopathological picture. The MSC treatment resulted in fewer inflammatory cells than in the DMH group. Therefore, our findings suggest that BMCs have antitumor effects by modulating the cellular redox status and down-regulating the pro-inflammatory genes. Thus, BMCs may provide therapeutic value for colon cancer treatment.

The Antioxidant and Antitumor Efficiency of Litophyton sp. Extract in DMH-Induced Colon Cancer in Male Rats

“…The increased levels of pro-inflammatory cytokines (TNF-& IL-1β), and tumor markers (CEA, CA19.9 and AFP) matched with a decrease in apoptotic biomarkers (CD4+) in colon cancer-bearing rats are in line with other earlier research [ 1 , 4 , 19 ]. Reactive oxygen species (ROS) production significantly contributes to oxidant/antioxidant imbalance.…”

“…Regarding the histological examination, the results illustrated that rats of the control group showed normal histological features of colon architecture that matched with the finding of Alkhuriji et al [ 4 ]; in contrast, the cancerous colon rats exhibited malignant appearances, evidenced by the elongation or oval hyperchromatic nuclei of the epithelium and glands, with the destruction of basement membrane that was similar to the finding of [ 43 ]. Destruction of the lining epithelium with leukocytic infiltrations is concurrent with [ 2 , 44 ] findings.…”

“…However, colon cancer is frequently discovered when it is advanced and the symptoms are clear [ 3 ]. Multiple tumor suppressor genes and oncogenes undergo genetic changes that cause colorectal carcinogenesis, a multi-step process that transforms healthy colonic epithelia into metastatic cancer [ 4 ]. Additionally, colon cancer is typically a pathological result of ongoing oxidative stress, which results in DNA damage, mutations in cancer-related genes, and a cycle of cell death, mutation, and excessive creation of reactive oxygen species (ROS) and reactive nitrogen species (RNS).…”

Mesenchymal Stem Cell-Based Therapy For Advanced Colorectal Cancer: Potential Mechanisms Of Therapy And Associated Risks

“…This paracrine activity includes the secretion of soluble molecules such as growth factors, cytokines, chemokines, and the release of extracellular vesicles that contain a wide variety of molecules such as mRNA, proteins, and microRNAs. Because of their paracrine function, mesenchymal stem cells exhibit immunosuppressive properties that promote tumor targeting in heterogeneous malignancies, thereby circumventing current obstacles in gene therapy [30].…”

Folate-Decorated Cross-Linked Cytochrome c Nanoparticles for Active Targeting of Non-Small Cell Lung Carcinoma (NSCLC)

“…During Cyt c-mediated apoptosis, the apoptosome formation (Apaf-1/Cyt c complex), which cleaves procaspase-9 to active caspase 9, is a critical event responsible for activating effector caspases 3 and 7, which mediate apoptosis [ 12 , 13 ]. Indeed, using a drug delivery system to transport Cyt c into the cytoplasm of cancer cells could help overcome any failure in activating the intrinsic or ‘mitochondrial’ apoptotic signaling pathway that prevents Cyt c release [ 10 , 14 , 15 ]. Hence, Cyt c has drawn the attention of groups in the field for its potential to be developed into a highly effective and selective anticancer drug [ 13 ].…”