Apoptotic and anti‐Warburg effect of Morusin via ROS mediated inhibition of FOXM1/c‐Myc signaling in prostate cancer cells

Abstract

Though Morusin is known to induce apoptotic, antiprolifertaive, and autophagic effects through several signaling pathways, the underlying molecular mechanisms of Morusin still remain unclear until now. To elucidate antitumor mechanism of Morusin, cytotoxicity assay, cell cycle analysis, Western blotting, TUNEL assay, RNA interference, immunofluorescense, immunoprecipitation, reactive oxygen species (ROS) measurement, and inhibitor study were applied in this study. Morusin enhanced cytotoxicity, increased the number of TUNEL positive cells, sub‐G1 population and induced the cleavages of PARP and caspase3, attenuated the expression of HK2, PKM2, LDH, c‐Myc, and Forkhead Box M1 (FOXM1) along with the reduction of glucose, lactate, and ATP in DU145 and PC3 cells. Furthermore, Morusin disrupted the binding of c‐Myc and FOXM1 in PC‐3 cells, which was supported by String and cBioportal database. Notably, Morusin induced c‐Myc degradation mediated by FBW7 and suppressed c‐Myc stability in PC3 cells exposed to MG132 and cycloheximide. Also, Morusin generated ROS, while NAC disrupted the capacity of Morusin to reduce the expression of FOXM1, c‐Myc, pro‐PARP, and pro‐caspase3 in PC‐3 cells. Taken together, these findings provide scientific evidence that ROS mediated inhibition of FOXM1/c‐Myc signaling axis plays a critical role in Morusin induced apoptotic and anti‐Warburg effect in prostate cancer cells. Our findings support scientific evidence that ROS mediated inhibition of FOXM1/c‐Myc signaling axis is critically involved in apoptotic and anti‐Warburg effect of Morusin in prostate cancer cells.

Investigating the molecular mechanism of Mori Cortex against osteosarcoma by bioinformatics analysis and in vitro experimental

“…[ 21 ] Meanwhile, Morusin can inhibit the promotion of prostate cancer cell apoptosis and counteract the Warburg effect by suppressing the ROS-mediated FOXM1/c-Myc signaling axis. [ 12 ] In the simulated pathway generated based on KEGG enrichment, the AKT and ERK pathways are the key signaling pathways for Mori Cortex’s anti-OS cellular responses. Numerous studies have shown that AKT plays a pivotal role in various cellular processes, such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration.…”

“…[ 9 – 11 ] Morusin is a typical prenylated flavonoid compound found in Mori Cortex. [ 12 ] Previous studies have reported that Morusin exerts anticancer activity against melanoma by activating the MAPK/STAT3 signaling pathway. [ 13 ] Furthermore, Morusin can induce apoptosis in lung cancer cells by increasing intracellular ROS levels and inhibiting the PI3K/AKT pathway.…”

Gastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran

“…Table 1 shows a comprehensive summary of these compounds and their distribution within the Morus alba L. tree. Against prostate [20] and ovarian cancer [21], as well as melanoma [21,22] Against colorectal [23], breast [24], gastric [25], and prostate cancer [26], as well as leukemia [27], and glioblastoma [ Against lung [28,29], gastric [30,31], colorectal [32], breast [33], kidney [34], ovarian [35], liver [36], and prostate cancer [37], as well as leukemia [38] and melanoma [39] Against cervical [42], breast [43][44][45], colorectal [46,47], gastric [48], prostate [49][50][51], lung [52][53][54], ovarian [55], liver [56,57], and pancreatic cancer [58], as well as melanoma [59] and renal cell carcinoma [60] Oxyresveratrol Against liver [64], lung [65,66], colorectal…”