Hopea odorata Extract Can Efficiently Kill Breast Cancer Cells and Cancer Stem-Like Cells in Three-Dimensional Culture More Than in Monolayer Cell Culture.

INTRODUCTION: The breast cancer cells with CD44+CD24- phenotype are known to play an important role in tumorigenesis, drug resistance, and cancer recurrence. Breast cancer cells with CD44+CD24- phenotype are cultured in three-dimensional (3D) stereotype showing the recapitulation of tumors in vivo such as cell differentiation, heterogeneity, and microenvironment. Using this 3D model in anti-cancer compound research results in a more accurate reflection than conventional monolayer cell culture. This study aimed to identify the antitumor activity of Hopea odorata methanol extract (HO-MeOH-E) on breast cancer cells and cancer stem-like cells in both models of three-dimensional culture (3D) and monolayer cell culture (2D). METHODS: HO-MeOH-E was produced from Hopea odorata plant. The VN9 breast cancer cells (VN9) were collected and expanded from the previous study. The breast cancer stem-like cells (VN9CSC) were sorted from the VN9 based on phenotype CD44+CD24-. Both VN9 and VN9CSC were used to culture in monolayer culture (2D) and organoids (3D) before they were used to treat with HO-MeOH-E. Two other anticancer drugs, doxorubicin and tirapazamine, were used as references. The antitumor activities of extracts and drugs were determined via two assays: antiproliferation using the Alamar blue assay and cell cycle assay. RESULTS: The results showed that HO-MeOH-E was sensitive to both VN9 and VN9CSC in 3D more than 2D culture (IC50 on 3D organoids 144.8 ± 2.172 µg/mL and on 2D 340.2 ± 17.01 µg/mL for VN9CSC (p < 0.001); IC50 on 3D organoids 2055 ± 82.2 µg/mL and on 2D 430.6 ± 8.612 µg/mL for VN9 (p < 0.0001), respectively). HO-MeOH-E inhibits VN9CSC proliferation by blocking S phase and increasing the populations of apoptotic cells; this is consensus to the effect of tirapazamine (TPZ) which is used in hypoxia-activated chemotherapy. CONCLUSION: Taken these results, HO-MeOH-E has the potential effect in hypoxia-activated chemotherapy specifically on breast cancer stem-like cells with CD44+CD24- phenotype.

Intravenous Infusion of Human Adipose Tissue-Derived Mesenchymal Stem Cells to Treat Type 1 Diabetic Mellitus in Mice: An Evaluation of Grafted Cell Doses.

Mesenchymal stem cell (MSC) transplantation is a novel treatment for diabetes mellitus, especially type 1 diabetes. Many recent publications have demonstrated the efficacy of MSC transplantation on reducing blood glucose and increasing insulin production in both preclinical and clinical trials. However, the investigation of grafted cell doses has been lacking. Therefore, this study aimed to evaluate the different doses of MSCs on treatment of type 1 diabetes in mouse models. MSCs were isolated and expanded from human adipose tissue. Streptozotocin (STZ)-induced diabetic mice were divided into two groups that were intravenously transfused with two different doses of human MSCs: 106 or 2.106 cells/mouse. After transplantation, both grafted and placebo mice were monitored weekly for their blood glucose levels, glucose and insulin tolerance, pancreatic structural changes, and insulin production for 56 days after transplantation. The results showed that the higher dose of MSCs (2.106 cells/mouse) remarkably reduced death rate. The death rates were 50%, 66%, and 0% in placebo group, low-dose (1.106 MSCs) group, and high-dose (2.106 MSCs) group, respectively, after 56 days of treatment. Moreover, blood glucose levels were lower for the high-dose group compared to other groups. Glucose and insulin tolerance, as well as insulin production, were significantly improved in mice transplanted with 2.106 cells. The histochemical analyses also support these results. Thus, a higher (e.g., 2.106) dose of MSCs may be an effective dose for treatment of type 1 diabetes mellitus.