25-hydroxycholesterol–induced cell death via activation of ROCK/LIMK/cofilin axis in colorectal cancer cell spheroids

Hitsuda, Ayaho; Dan, Reona; Urakawa, Ayaka; Hiraoka, Yasuna; Murakami, Chiho; Yamamoto, Hideya; Tanaka, Akihiro

doi:10.1016/j.jsbmb.2021.106037

Cited by 9 publications

(5 citation statements)

References 36 publications

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“…1A). We previously established a system to stably generate colorectal cancer spheroids and measure their growth (Hitsuda et al 2022). In this system, one colorectal cancer spheroid per well is produced with a diameter greater than 300 µm after 7 days of incubation (Fig.…”

Section: Resultsmentioning

confidence: 99%

Physiological Methylmalonic Acid Contributes to Cell Growth via Mitochondrial Dysfunction in Colorectal Cancer Cell Spheroids

Tanaka,

Murakami,

Yamamoto

2023

Preprint

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Methylmalonic acid (MMA) is a small molecule produced during the metabolism of branched-chain amino acids. Recently, it was reported that the blood concentration of MMA increased with age and that it also promoted lung cancer metastasis. However, little is known about how it affects cancers other than lung cancer. In this study, we examined the influences of MMA on colorectal cancer cell spheroids. We found that MMA promoted proliferation of colorectal cancer spheroids in a glutamine-dependent manner at physiological concentrations; MMA induced mitochondrial reactive oxygen species generation, which in turn affected the promotion of cell growth. Methylmalonic acid treatment also induced a metabolic shift to the glycolytic system. These results suggest that physiological concentrations of MMA may promote cancer cell proliferation by decreasing mitochondrial function and inducing a metabolic shift, and add new insights into the effect of aging on cancer.

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Section: Resultsmentioning

confidence: 99%

Physiological Methylmalonic Acid Contributes to Cell Growth via Mitochondrial Dysfunction in Colorectal Cancer Cell Spheroids

Tanaka,

Murakami,

Yamamoto

2023

Preprint

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“…CRC is a malignancy that progresses to the gastrointestinal tract. CRC has a high global incidence rate and high fatality rate [17] and is the cause of approximately 600,000 deaths each year [18]. Currently, CRC treatment primarily involves systematic treatment methods, such as surgery, radiotherapy, chemotherapy, and molecular targeted drugs [19].…”

Section: Discussionmentioning

confidence: 99%

Cynaroside Induces G1 Cell Cycle Arrest by Downregulating Cell Division Cycle 25A in Colorectal Cancer

Lei,

Cao,

Zeng

et al. 2024

Molecules

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Natural chemicals derived from herbal plants have recently been recognized as potentially useful treatment alternatives owing to their ability to target a wide range of important biological molecules. Cynaroside is one of these natural compounds with promising anticancer activity for numerous tumor types. Nevertheless, the anticancer effects and molecular mechanisms of action of cynaroside on colorectal cancer (CRC) remain unclear. In this study, cynaroside was found to markedly inhibit CRC cell proliferation and colony formation in vitro. Cynaroside also inhibited cell proliferation in vivo and decreased the expression of KI67, a cell nuclear antigen. RNA sequencing revealed 144 differentially expressed genes (DEGs) in HCT116 cells and 493 DEGs in RKO cells that were enriched in the cell cycle signaling pathway. Cell division cycle 25A (CDC25A), a DEG widely enriched in the cell cycle signaling pathway, is considered a key target of cynaroside in CRC cells. Cynaroside also inhibited DNA replication and arrested cells in the G1/S phase in vitro. The expression levels of CDC25A and related G1-phase proteins were significantly elevated after CDC25A overexpression in CRC cells, which partially reversed the inhibitory effect of cynaroside on CRC cell proliferation and G1/S-phase arrest. In summary, cynaroside may be used to treat CRC as it inhibits CDC25A expression.

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“…The conventional view is that the activity of LIMK/Cofilin stabilizes the actin cytoskeleton [ 54 , 55 , 56 ]. However, the contribution of axin remodeling to LIMK/Cofilin in the generation of mature and vascularized COs is currently unclear.…”

Section: Discussionmentioning

confidence: 99%

The Activation of the LIMK/Cofilin Signaling Pathway via Extracellular Matrix–Integrin Interactions Is Critical for the Generation of Mature and Vascularized Cardiac Organoids

Noh

Choi

Song

et al. 2023

Cells

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The generation of mature and vascularized human pluripotent stem cell-derived cardiac organoids (hPSC-COs) is necessary to ensure the validity of drug screening and disease modeling. This study investigates the effects of cellular aggregate (CA) stemness and self-organization on the generation of mature and vascularized hPSC-COs and elucidates the mechanisms underlying cardiac organoid (CO) maturation and vascularization. COs derived from 2-day-old CAs with high stemness (H-COs) and COs derived from 5-day-old CAs with low stemness (L-COs) were generated in a self-organized microenvironment via Wnt signaling induction. This study finds that H-COs exhibit ventricular, structural, metabolic, and functional cardiomyocyte maturation and vessel networks consisting of endothelial cells, smooth muscle cells, pericytes, and basement membranes compared to L-COs. Transcriptional profiling shows the upregulation of genes associated with cardiac maturation and vessel formation in H-COs compared with the genes in L-COs. Through experiments with LIMK inhibitors, the activation of ROCK-LIMK-pCofilin via ECM–integrin interactions leads to cardiomyocyte maturation and vessel formation in H-COs. Furthermore, the LIMK/Cofilin signaling pathway induces TGFβ/NODAL and PDGF pathway activation for the maturation and vascularization of H-COs. The study demonstrates for the first time that LIMK/Cofilin axis activation plays an important role in the generation of mature and vascularized COs.

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25-hydroxycholesterol–induced cell death via activation of ROCK/LIMK/cofilin axis in colorectal cancer cell spheroids

Cited by 9 publications

References 36 publications

Physiological Methylmalonic Acid Contributes to Cell Growth via Mitochondrial Dysfunction in Colorectal Cancer Cell Spheroids

Physiological Methylmalonic Acid Contributes to Cell Growth via Mitochondrial Dysfunction in Colorectal Cancer Cell Spheroids

Cynaroside Induces G1 Cell Cycle Arrest by Downregulating Cell Division Cycle 25A in Colorectal Cancer

The Activation of the LIMK/Cofilin Signaling Pathway via Extracellular Matrix–Integrin Interactions Is Critical for the Generation of Mature and Vascularized Cardiac Organoids

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