Targeting estrogen receptors in colorectal cancer

Maingi, Joyce Wanjiru; Shu, Tang; Liu, Sirui; Ngenya, Watson; Bao, Endong

doi:10.1007/s11033-020-05414-6

Cited by 25 publications

(22 citation statements)

References 46 publications

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“…Targeted activation of ERβ represents a novel clinical approach for management and prevention of cancers (Bolli & Marino, 2011; Williams, DiLeo, Niv, & Gustafsson, 2016) including colon cancer (Caiazza, Ryan, Doherty, Winter, & Sheahan, 2015; Maingi, Tang, Liu, Ngenya, & Bao, 2020). ERβ is a potent tumor suppressor and reduces cancer metastasis (Kyriakidis & Papaioannidou, 2016; Nguyen‐Vu et al., 2016; Stettner et al., 2007).…”

Section: Resultsmentioning

confidence: 99%

Piperine sensitizes radiation‐resistant cancer cells towards radiation and promotes intrinsic pathway of apoptosis

Shaheer

Somashekarappa

Lakshmanan

2020

Journal of Food Science

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Piperine, a bioactive alkaloid, is known to have anticancer activities. Hence, in this study, the effectiveness of piperine pretreatment as a strategy for radio‐sensitizing colorectal adenocarcinoma cell line (HT‐29) was analyzed. For this, HT‐29 cells were pretreated with piperine (12.5 and 25 µg/mL) and exposed to γ‐radiation (1.25 Gy) and analyzed for various effector pathways to elucidate the possible mode of action in comparison to individual treatments. The proliferation efficiency of the cells was analyzed by trypan blue dye exclusion assay and MTT assay. The synergistic effects of the combination treatment were analyzed with compuSyn software. Downstream signaling pathways leading to apoptosis were studied using flowcytometry, immunofluorescence, and immunoblot assays. It was observed that combination treatment arrested HT‐29 cells at G2/M phase nearly 2.8 folds higher than radiation treatment alone, inducing the radio‐resistant cells to undergo apoptosis through mitochondria‐dependent pathway. In addition, activation of caspase‐3 and cleavage of poly(ADP‐ribose) polymerases‐1, the key molecular events in apoptotic signaling, were significantly enhanced. Activation of estrogen receptor beta (ERβ), a nuclear hormone transcription factor promoting tumor suppression represents a novel clinical advance towards management and prevention of cancers. Interestingly, the expression of ERβ was increased in the cells treated with piperine. In conclusion, piperine pretreatment enhances radio‐sensitization in HT‐29 cells by inducing the cells to undergo apoptosis hence, can be used as a classic candidate for colon cancer sensitization towards radiotherapy. Practical Application Piperine induces enhanced radiosensitization of colon cancer cell line (HT‐29) by interfering with the cancer cell line proliferation, DNA damage, and apoptosis.

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Section: Resultsmentioning

confidence: 99%

Piperine sensitizes radiation‐resistant cancer cells towards radiation and promotes intrinsic pathway of apoptosis

Shaheer

Somashekarappa

Lakshmanan

2020

Journal of Food Science

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“…Given the preponderance for a lower incidence of CRC in pre-menopausal women, the weight of clinical and experimental evidence points to estrogen as the major sex steroid hormone underlying sexual dimorphism in CRC. The protective role of estrogen in the female against colorectal cancer has been mainly associated with expression levels of the ERβ in intestinal epithelial cells ( 71 , 72 ). The ERβ1, ERβ2, and ERβ5 isoforms are expressed in the colon with variable levels along the crypt axis ( 73 ) and are reduced in tumor cells compared to normal colon ( 74 , 75 ).…”

Section: Sexual Dimorphism Of Hormones and Receptors In Crcmentioning

confidence: 99%

Sexual Dimorphism in Colon Cancer

et al. 2020

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A higher incidence of colorectal cancer (CRC) is found in males compared to females. Young women (18–44 years) with CRC have a better survival outcome compared to men of the same age or compared to older women (over 50 years), indicating a global incidence of sexual dimorphism in CRC rates and survival. This suggests a protective role for the sex steroid hormone estrogen in CRC development. Key proliferative pathways in CRC tumorigenesis exhibit sexual dimorphism, which confer better survival in females through estrogen regulated genes and cell signaling. Estrogen regulates the activity of a class of Kv channels (KCNQ1:KCNE3), which control fundamental ion transport functions of the colon and epithelial mesenchymal transition through bi-directional interactions with the Wnt/β-catenin signalling pathway. Estrogen also modulates CRC proliferative responses in hypoxia via the novel membrane estrogen receptor GPER and HIF1A and VEGF signaling. Here we critically review recent clinical and molecular insights into sexual dimorphism of CRC biology modulated by the tumor microenvironment, estrogen, Wnt/β-catenin signalling, ion channels, and X-linked genes.

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“…Aside from its function as a sexual hormone, estrogen or estradiol play an important role in cell turnover. It acts as a bridge for ion transport that regulates cells’ pH, intracellular ions, and several protein activations[ 29 ]. Estrogen also exudes anti-inflammatory properties due to its ability to bond and modulate leukocytes including natural killer cell, neutrophils, dendritic cells, etc [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Prediction of hereditary nonpolyposis colorectal cancer using mRNA MSH2 quantitative and the correlation with nonmodifiable factor

Tedjasaputra¹,

Hatta²,

Massi³

et al. 2021

WJGP

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BACKGROUND Hereditary non-polyposis colon cancer is a dominantly inherited syndrome of colorectal cancer (CRC), with heightened risk for younger population. Previous studies link its susceptibility to the DNA sequence polymorphism along with Amsterdam and Bethesda criteria. However, those fail in term of applicability. AIM To determine a clear cut-off of MSH2 gene expression for CRC heredity grouping factor. Further, the study also aims to examine the association of risk factors to the CRC heredity. METHODS The cross-sectional study observed 71 respondents from May 2018 to December 2019 in determining the CRC hereditary status through MSH2 mRNA expression using reverse transcription-polymerase chain reaction and the disease’s risk factors. Data were analyzed through Chi-Square, Fischer exact, t-test, Mann-Whitney, and multiple logistics. RESULTS There are significant differences of MSH2 within CRC group among tissue and blood; yet, negative for significance between groups. Through the blood gene expression fifth percentile, the hereditary CRC cut-off is 11059 fc, dividing the 40 CRC respondents to 32.5% with hereditary CRC. Significant risk factors include age, family history, and staging. Nonetheless, after multivariate control, age is just a confounder. Further, the study develops a probability equation with area under the curve 82.2%. CONCLUSION Numerous factors have significant relations to heredity of CRC patients. However, true important factors are staging and family history, while age and others are confounders. The study also established a definite cut-off point for heredity CRC based on mRNA MSH2 expression, 11059 fc. These findings shall act as concrete foundations on further risk factors and/or genetical CRC future studies.

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Targeting estrogen receptors in colorectal cancer

Cited by 25 publications

References 46 publications

Piperine sensitizes radiation‐resistant cancer cells towards radiation and promotes intrinsic pathway of apoptosis

Piperine sensitizes radiation‐resistant cancer cells towards radiation and promotes intrinsic pathway of apoptosis

Sexual Dimorphism in Colon Cancer

Prediction of hereditary nonpolyposis colorectal cancer using mRNA MSH2 quantitative and the correlation with nonmodifiable factor

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