Capsanthin induces G1/S phase arrest, erlotinib-sensitivity and inhibits tumor progression by suppressing EZH2-mediated epigenetically silencing of p21 in triple-negative breast cancer cells

Wu, Jiayan; Chien, Yi-Chung; Tsai, I-Chen; Hung, Chih-Chiang; Huang, Wei-Chien; Liu, Liang‐Chih; Yu, Yung-Luen

doi:10.18632/aging.202925

Cited by 5 publications

(3 citation statements)

References 23 publications

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“…This inhibition ultimately leads to the interruption of the cell cycle in G1 and S phases [ 48 , 49 ]. Downregulation of p21 is linked to tumor differentiation, invasion, proliferation, and metastasis in several studies [ 50 , 51 ]. Moreover, targeting p21 is a potential strategy for the treatment of tumors.…”

Section: Discussionmentioning

confidence: 99%

d-Borneol enhances cisplatin sensitivity via p21/p27-mediated S-phase arrest and cell apoptosis in non-small cell lung cancer cells and a murine xenograft model

Yuan

et al. 2022

Cell Mol Biol Lett

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Background Cisplatin (CDDP) is commonly used to treat non-small cell lung cancer (NSCLC), but the appearance of drug resistance greatly hinders its efficacy. Borneol may promote drug absorption; however, synergism between borneol and CDDP in suppressing NSCLC is not clearly understood. Hence, we investigated borneol as a novel chemosensitizer to support chemotherapeutic efficacy and reduce side effects. Methods We compared viability after exposure to d-borneol, l-borneol, and synthetic borneol in two NSCLC cell lines, A549 and H460, and selected the most sensitive cells. We then assessed synergy between borneol forms and CDDP in cisplatin-resistant NSCLC cells, H460/CDDP. Next, we identified effective concentrations and exposure times. Subsequently, we evaluated cell migration via wound healing and cell proliferation via clone formation assay. Then, we focused on P-glycoprotein (P-gp) function, cell cycle, apoptosis, and RNA sequencing to elucidate underlying molecular mechanisms for synergy. Finally, we used an H460/CDDP xenograft tumor model to verify antitumor activity and safety in vivo. Data were examined using one-way analysis of variance (ANOVA) for multiple datasets or t-test for comparisons between two variables. Results d-Borneol was more effective in H460 than A549 cells. d-Borneol combined with CDDP showed greater inhibition of cell proliferation, migration, and clone formation in H460/CDDP cells than CDDP alone. RNA sequencing (RNA-seq) analysis identified differentially expressed genes enriched in cell cycle pathways. The impact of d-borneol on CDDP chemosensitivity involved arrest of the cell cycle at S phase via p27/p21-mediated cyclinA2/D3-CDK2/6 signaling and activation of intrinsic apoptosis via p21-mediated Bax/Bcl-2/caspase3 signaling. Further, d-borneol ameliorated drug resistance by suppressing levels and activity of P-gp. Cotreatment with d-borneol and CDDP inhibited tumor growth in vivo and reduced CDDP-caused liver and kidney toxicity. Conclusions d-Borneol increased the efficacy of cisplatin and reduced its toxicity. This compound has the potential to become a useful chemosensitizer for drug-resistance NSCLC.

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Section: Discussionmentioning

confidence: 99%

d-Borneol enhances cisplatin sensitivity via p21/p27-mediated S-phase arrest and cell apoptosis in non-small cell lung cancer cells and a murine xenograft model

Yuan

et al. 2022

Cell Mol Biol Lett

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“…Thus, dysregulation of the cell cycle due to overexpression of EZH2 is prevented and p21 levels are upregulated, which results in cell-cycle arrest at the G1/S phase, and prevention of tumor proliferation. It has also been found to act synergistically with erlotinib (tyrosine kinase inhibitor), and increase its sensitivity in chemotherapy-resistant cells [14]. RL71, a second-generation curcumin analog, triggers uncontrolled autophagic cell death, exhibiting effective anticancer activity in TNBC cells.…”

Section: Natural Analogsmentioning

confidence: 99%

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Injeti¹

2022

Fut J. Pharm & H. Sci

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“…P21 is an inhibitor of cyclin-dependent kinase and multiple studies demonstrated a tumor suppressive role of P21 in tumorigene-sis [38,39]. The main mechanism of P21 to prevent cell cycle progression is to inhibit the expression of CCNE1 and PCNA, thereby reducing the expression of tumor growth factor and blocking the progress of cell cycle [40][41][42]. In addition to PCNA, we also focused on other two proteins, CCNE1 and P21, that are related to cell proliferation [36].…”

Section: Mechanisms Of Scs Inhibited Colorectal Cancer 291 Scs Inhibits the Growth Of Ht-29 By Regulating The Expression Of Genes Involvementioning

confidence: 99%

The Regulatory Network of Sturgeon Chondroitin Sulfate on Colorectal Cancer Inhibition by Transcriptomic and Proteomic Analysis

Shen

et al. 2021

IJMS

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Chondroitin sulfate (CS) is a food-derived bioactive substance with multiple biological functions, which exists in animal cartilage and/or bone. Sturgeon, a type of cartilaginous fish, is rich in CS. Our recent study demonstrated the effect of sturgeon chondroitin sulfate (SCS) on reducing colorectal cancer cell proliferation and tumor formation. However, the molecular mechanisms of its anticancer activity remain unknown. In this study, the cell proliferation assay and flow cytometric analysis were used to examine the cell viability and apoptosis of colon cancer cell HT-29 cells and normal colonic epithelial cell NCM460 cells. Transcriptomic and proteomic studies were used to identify the main targets of SCS. SCS showed little effect on the genes/proteins expression profile of NCM460 cells but more sensitive to HT-29, in which 188 genes and 10 proteins were differentially expressed after SCS treatment. Enrichment analysis of those genes/proteins showed that the majority of them are involved in DNA replication, cell cycle progression and apoptosis. Quantitative RT-PCR and Western blot were used to determine essential genes/proteins and networks targeted by SCS to exert inhibiting the development of colorectal cancer function. This study provided great insights into developing food-derived novel therapeutics for colorectal cancer treatment.

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Capsanthin induces G1/S phase arrest, erlotinib-sensitivity and inhibits tumor progression by suppressing EZH2-mediated epigenetically silencing of p21 in triple-negative breast cancer cells

Cited by 5 publications

References 23 publications

d-Borneol enhances cisplatin sensitivity via p21/p27-mediated S-phase arrest and cell apoptosis in non-small cell lung cancer cells and a murine xenograft model

d-Borneol enhances cisplatin sensitivity via p21/p27-mediated S-phase arrest and cell apoptosis in non-small cell lung cancer cells and a murine xenograft model

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The Regulatory Network of Sturgeon Chondroitin Sulfate on Colorectal Cancer Inhibition by Transcriptomic and Proteomic Analysis

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