Fatemeh Safari

Breast cancer ranks as the foremost cause of death among women worldwide. Despite the availability of various treatment options such as chemotherapy, radiotherapy, and hormone therapy, these current strategies are often ineffective and thereby, there is a constant necessity to explore new therapeutic avenues with minimal side effects and enhanced efficacy. The application of cell-based therapy and the use of stem cells or their derivatives in treating diseases, including cancer, have become well established. Herein, we aimed to investigate the impact of the secretome of human amniotic mesenchymal stem cells (hAMSCs) on MDA-MB-231 cancer cells (with a mutant p53 R280K background) focusing on the p53/MDM2/p21/ATM/ATR/PUMA/Bax/Caspase3 signaling pathways. To achieve this, we developed a co-culture system utilizing 6 well plates transwell. After 72 h, cell death and cell cycle arrest in hAMSCs-treated MDA-MB-231 cells were assessed by analyzing the aforementioned signaling pathways using Western blot and flow cytometry. The exposure time for MTT assay was 48 h, and for DAPI staining, it was 24 h. Our results revealed an increase in the expression levels of ATM, ATR, CHK2, p53, p-p53, PUMA, Bax, cleaved caspase 3, p21, RB, and p-RB, alongside a reduction in MDM2 expression. These findings suggest that hAMSCs secretome promotes cell death and induces S phase cell cycle arrest in MDA-MB-231 cells, suggesting its potential as a novel approach in cancer therapy.

Background: Colon cancer is recognized as one of the predominant reasons of death globally. The ongoing cancer treatment techniques have not been successful; so, a strong and unique platform is needed. Interestingly, it has been discovered that stem cells offer a valuable and promising platform in cancer treatment. The goal of this study is to explore the influences of hAMSCs secretome on HT‐29 colon cancer cells by analyzing TNF‐α/TGF‐βR/c‐MYC signaling pathway, expression of interleukins (IL)‐4/6/8, and cyclin‐dependent kinase (CDK) inhibitory proteins (p15 ^INK4B and p21 ^CIP1 ) using a hanging drop 3D cell culture model. Methods: In this study, a coculture system was employed. After 3 days, hAMSCs' secretome was collected and its effects on tumor formation, inflammation, and cell invasion were analyzed using Western blot, scratch assay, qPCR, and ELISA. Results: The study revealed a decrease in the TGF‐βR/SMADs/c‐MYC signaling pathway and an increase in levels of p15 ^INK4B , p21 ^CIP1 , TNF‐α, and IL‐4/6/8. Additionally, a decrease in invasion was detected in HT‐29 cells treated with hAMSCs. Conclusions: Our results could be useful in developing a new approach to treating cancer using hAMSCs' secretome.

Prostate cancer (PC) ranks as the fifth major cause of cancer‐related fatalities globally. Exploring new methods with high efficacy and low side effects by using new compounds is always desired. Tea is considered the second most commonly consumed beverage among the population of the world. Polyphenols (or catechins) in green tea play a significant role in cellular signaling pathways. Herein, we evaluate the effects of green tea extract on suppression of cellular proliferation through testing the expression of miR‐34a in PC3 prostate cancer cells. In this respect, PC3 prostate cancer cells were cultured and treated with green tea extract for 48 h. By using the qRT‐PCR method, the expression of miR‐34a was analyzed. Moreover, the expression of key proteins to regulate cellular proliferation, such as prostate specific antigen (PSA), AKT, cyclin dependent kinase 1 (CDK1), cyclin B1, c‐Myc, p53, and phospho‐androgen receptor (p‐AR) was evaluated by using western blot. Our results indicated the induction of miR‐34a, p53, and the inhibition of cyclin B1, p‐AR, CDK1, p‐AKT, PSA, c‐Myc, and p‐CDK1. Our findings can be used to design anti‐tumor regimens that utilize natural product ingredients. However, additional research will be needed to identify anticancer activities of green tea via miR‐34a in prostate cancer cells.

Cancer evades therapy by multiple mechanisms, leading to uncontrolled cell growth and metastasis. Targeted therapies have shown promise in treating cancer by focusing on pathways within cancer cells. The PEAK family, comprising PEAK1 (SgK269), PEAK2 (SgK223/Pragmin), and the latest addition, PEAK3 (C19orf35), plays a crucial role in modulating cellular processes. Dysregulation and hyperactivity of these proteins, through overexpression or mutations, are associated with a wide range of cancers. This review delves into the different roles of the PEAK family members in regulating cell signaling pathways and highlights their potential in cancer therapy.

Cancer is a predominant testimony of human departure in a global way. Current therapeutic strategies are not sufficient, and thereby exploring a new approach with high efficacy and influence is desired. The intention of this research is to distinguish a novel therapeutic burgeon in colon cancer plus employing the human mesenchymal stem cells (hAMSCs) secretome as a new tool in colon cancer therapy. For this purpose, 30 pieces from patients afflicted with colon cancer were provided. The expressing level of IRSp53 was evaluated using quantitative real‐time PCR (qRT‐PCR). Then, a coculture procedure utilizing six well plates transwell was applied. Since 72 h, tumor increment was surveyed in HT‐29 cells treated by hAMSCs through the EGFR/c‐Src/IRSp53/p‐AKT/p‐Stat3/cyclin D1 signaling cascade. Our results indicated IRSp53 upregulation in patients suffering colon cancer and reduction of EGFR/c‐Src/IRSp53/p‐AKT/p‐Stat3/cyclin D1 signaling pathway, which led to suppression of cell proliferation in the hAMSCs‐treated HT‐29 colon cancerous cells. We also found tumor growth suppression as well as IRSp53 expression in hAMSCs‐treated HT‐29 colon cancerous cell line using a 3D cell culturing technique. Our study’s findings indicate that colon cancer therapy could benefit from targeting IRSp53 and that MSCs could be a valuable therapeutic option for stopping the proliferation of colon cancer cells. This could be achieved through the EGFR/c‐Src/IRSp53/p‐AKT/p‐Stat3/cyclin D1 signaling pathway.