Elucidating the pharmacological effects of Compound Kushen injection on MYC-P15-CCND1 signaling pathway in nasopharyngeal carcinoma - An in vitro study

Wu, Zhishan; Wu, Chao; Shi, Jian; Huang, Zhihong; Lu, Shan; Tan, Yingying; You, Rongli; Lü, Hai; Huang, Jiaqi; Guo, Siyu; Gao, Yifei; Jin, Zhe; Tao, Xiaoyu; You, Leiming; Wu, Jiarui

doi:10.1016/j.jep.2023.116702

Cited by 2 publications

(1 citation statement)

References 28 publications

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“…Previous studies document co-expression of MYBL1 and MYC genes. Co-expression of MYBL1 and MYC are detected in pharynx cancers [ 55 ], adenoid cystic carcinoma [ 56 ] and breast, ovarian and lung cancers [ 13 , 45 , 57 , 58 ]. For the most part, data presented in this study are consistent with previous observations showing over-expression and amplification of MYC in breast cancers [ 23 , 59 , 60 ], with a notable correlation between MYBL1 and MYC amplification alterations in the TCGA 1015 patient sample TNBC dataset.…”

Section: Discussionmentioning

confidence: 99%

Characterization of MYBL1 Gene in Triple-Negative Breast Cancers and the Genes’ Relationship to Alterations Identified at the Chromosome 8q Loci

Player,

Cunningham,

Philio

et al. 2024

IJMS

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The MYBL1 gene is a strong transcriptional activator involved in events associated with cancer progression. Previous data show MYBL1 overexpressed in triple-negative breast cancer (TNBC). There are two parts to this study related to further characterizing the MYBL1 gene. We start by characterizing MYBL1 reference sequence variants and isoforms. The results of this study will help in future experiments in the event there is a need to characterize functional variants and isoforms of the gene. In part two, we identify and validate expression and gene-related alterations of MYBL1, VCIP1, MYC and BOP1 genes in TNBC cell lines and patient samples selected from the Breast Invasive Carcinoma TCGA 2015 dataset available at cBioPortal.org. The four genes are located at chromosomal regions 8q13.1 to 8q.24.3 loci, regions previously identified as demonstrating a high percentage of alterations in breast cancer. We identify alterations, including changes in expression, deletions, amplifications and fusions in MYBL1, VCPIP1, BOP1 and MYC genes in many of the same patients, suggesting the panel of genes is involved in coordinated activity in patients. We propose that MYBL1, VCPIP1, MYC and BOP1 collectively be considered as genes associated with the chromosome 8q loci that potentially play a role in TNBC pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Characterization of MYBL1 Gene in Triple-Negative Breast Cancers and the Genes’ Relationship to Alterations Identified at the Chromosome 8q Loci

Player,

Cunningham,

Philio

et al. 2024

IJMS

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Active fraction from clove inhibits colorectal cancer cell proliferation by downregulating M2-type pyruvate kinase to reduce aerobic glycolysis

Liu,

Xing,

Guo

et al. 2024

Preprint

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Background Aerobic glycolysis contributes to the high rate of metabolism in tumour cells and colorectal cancer is one of the highly metabolic malignancies. Highly expressed M2-type pyruvate kinase (PKM2) promotes tumour cell proliferation and migration as the rate-limiting enzyme of aerobic glycolysis. Previously we have shown that the active fraction from clove (AFC) can inhibit the growth of colon cancer cells in vitro. However, the mechanism of action regarding the anti-colon cancer activity of AFC, especially in aerobic glycolysis, has not been adequately investigated. Methods In vitro anti-colon cancer activity was assessed by CCK8 assay and colony formation assay, and changes in aerobic glycolytic capacity were assessed by evaluating changes in glucose consumption, lactate production, pyruvate kinase activity and pyruvate production. HCT116 cells xenograft model in nude mice was established to measure the anti-colon cancer activity of AFC in vivo. Mechanism of action studies involved western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR), small interfering RNA (siRNA) knockdown transfection, and immunohistochemistry. Results The present study confirmed those findings by showing that the active fraction significantly inhibited the growth of five lines of colon cancer cells (HT29, SW620, Caco-2, HCT116 and LoVo). And we found that the active fraction reduced pyruvate kinase activity, glucose uptake, and production of pyruvate and lactate. It also downregulated M2-type pyruvate kinase (PKM2), c-myc and cyclin D1. Knockdown of PKM2 on its own mimicked the effects of active fraction, which could result in the ability to inhibit cell proliferation and aerobic glycolysis. Consistent with these results in cell culture, the active fraction significantly inhibited tumor growth and downregulated PKM2, c-myc and cyclin D1 in HCT116 xenografts in mice, while causing milder liver damage and weight loss than the conventional chemotherapeutic 5-fluorouracil (5-FU). Conclusion Our fndings indicate that AFC inhibits colon cancer growth by downregulating PKM2 to inhibit aerobic glycolysis and reduces tumour-specific high expression of c-myc and cyclin D1. Future work should explore how it downregulates pyruvate kinase in the first place, and the intrinsic mechanism between the down-regulation of PKM2 and the down-regulation of c-myc and cyclin D1.

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Elucidating the pharmacological effects of Compound Kushen injection on MYC-P15-CCND1 signaling pathway in nasopharyngeal carcinoma - An in vitro study

Cited by 2 publications

References 28 publications

Characterization of MYBL1 Gene in Triple-Negative Breast Cancers and the Genes’ Relationship to Alterations Identified at the Chromosome 8q Loci

Characterization of MYBL1 Gene in Triple-Negative Breast Cancers and the Genes’ Relationship to Alterations Identified at the Chromosome 8q Loci

Active fraction from clove inhibits colorectal cancer cell proliferation by downregulating M2-type pyruvate kinase to reduce aerobic glycolysis

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