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Prevention and Drug Treatment of Breast Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 16605

Special Issue Editor

Department of Biological Sciences, College of Science & Technology, Florida Agricultural and Mechanical University, Tallahassee, FL, USA
Interests: natural product; therapeutics; health promotion; nutraceuticals; metabolomics; medicinal chemistry; innovative technology (artificial intelligence and machine learning)
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Special Issue Information

Dear Colleagues,

Breast cancer is the most diagnosed type of cancer in women, and it has the second highest mortality rate in this group, following only lung cancer. Every year, an estimated 1–1.3 million breast cancer cases are diagnosed worldwide. Of these, approximately 15–20% of breast cancers in women are triple-negative breast cancer (TNBC), which is considered to be more aggressive and is often diagnosed in patients younger than 50 years old. Other types of breast cancer are more commonly diagnosed in people aged 60 or older. In addition to young women, TNBC disproportionately affects women of African and Hispanic descent than women of Caucasian descent. Asian women and non-Hispanic white women are less likely to be diagnosed with this type of cancer. Family history is a well-recognized and established risk factor for aggressive breast cancer. For example, about 70% of breast cancers diagnosed in people with an inherited BRCA mutation, particularly BRCA1, are triple-negative breast cancer. Other factors, such as environmental exposure to mixtures of chemicals, have been linked to an increased incidence of breast cancer in the United States and, in particular, among minority populations. Although family history (hereditary) risk factors associated with breast cancer are not modifiable, lifestyle and some environmental factors can be modified and prevented. A healthy lifestyle can be achieved by keeping a normal body weight, eating well or consuming a high amount of vegetables and fruit, lowering blood pressure, managing stress, maintaining enough physical activity, minimizing alcohol intake, quitting cigarette smoking, and reducing second-hand smoke exposure.

National Cancer Institute (NCI)-supported research has indicated that aggressive breast tumors are more common in younger African American and Hispanic women living in low socioeconomic status areas. This more aggressive form of breast cancer is less responsive to standard cancer treatments and is associated with a lower survival rate. The treatment of aggressive breast cancer remains a critical challenge in the medical community, because there are no targeted therapies and the prognosis remains modest. Moreover, there is an urgent need for the discovery and development of agent(s) efficacious to treat aggressive breast cancer. Studies have shown that there are alternative treatments to conventional drugs that might be effective in the management of TNBC. The peer-reviewed articles published in this Special Issue will highlight the drug treatment of breast cancer. In addition, this Special Issue will address the issues of preventive measures for breast cancer.  When considering your submission, please keep in mind that IJMS is a journal of molecular science.

Dr. Clement G. Yedjou
Guest Editor

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Keywords

  • breast cancer
  • drug treatment
  • traditional medicine
  • natural product
  • prevention
  • treatment

Published Papers (5 papers)

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Research

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13 pages, 3321 KiB  
Article
Antiproliferative Mechanisms of a Polyphenolic Combination of Kaempferol and Fisetin in Triple-Negative Breast Cancer Cells
by Mohd. Afzal, Abdullah Alarifi, Abdalnaser Mahmoud Karami, Rashid Ayub, Naaser A. Y. Abduh, Waseem Sharaf Saeed and Mohd. Muddassir
Int. J. Mol. Sci. 2023, 24(7), 6393; https://doi.org/10.3390/ijms24076393 - 29 Mar 2023
Cited by 5 | Viewed by 1585
Abstract
Herein, we investigate the combinatorial therapeutic effects of naturally occurring flavonoids kaempferol (K) and fisetin (F) on triple-negative breast cancer (TNBC: MDA-MB-231 cell line). Dose-dependent MTT assay results show that K and F exhibited cytotoxicity in MDA-MB-231 cells at 62 and 75 μM [...] Read more.
Herein, we investigate the combinatorial therapeutic effects of naturally occurring flavonoids kaempferol (K) and fisetin (F) on triple-negative breast cancer (TNBC: MDA-MB-231 cell line). Dose-dependent MTT assay results show that K and F exhibited cytotoxicity in MDA-MB-231 cells at 62 and 75 μM (IC50), respectively, after 24 h. However, combined K + F led to 40% and more than 50% TNBC cell death observed at 10 and 20 μM, respectively, which revealed the synergistic association of both. The combination of K and F was determined to be more effective in inhibiting cell viability than either of the agents alone. The morphological changes associated with significant apoptotic cell death were observed under a fluorescent microscope, strongly supporting the synergistic association between K and F. We also proposed that combining the effects of both polyphenols, as opposed to their individual effects, would increase their in vitro efficacy. Furthermore, we assessed the cell death pathway by the combinational treatment via reactive oxygen species-induced DNA damage and the mitochondrially mediated apoptotic pathway. This study reveals the prominent synergistic role of phytochemicals, which helps in elevating the therapeutic efficacy of dietary nutrients and that anticancer effects may be a result of nutrients that act in concert. Full article
(This article belongs to the Special Issue Prevention and Drug Treatment of Breast Cancer)
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25 pages, 4369 KiB  
Article
WNT3a Signaling Inhibits Aromatase Expression in Breast Adipose Fibroblasts—A Possible Mechanism Supporting the Loss of Estrogen Responsiveness of Triple-Negative Breast Cancers
by Alexander Kaiser, Gabriele Eiselt, Joachim Bechler, Otmar Huber and Martin Schmidt
Int. J. Mol. Sci. 2023, 24(5), 4654; https://doi.org/10.3390/ijms24054654 - 28 Feb 2023
Cited by 1 | Viewed by 1447
Abstract
Estrogen-dependent breast cancers rely on a constant supply of estrogens and expression of estrogen receptors. Local biosynthesis, by aromatase in breast adipose fibroblasts (BAFs), is their most important source for estrogens. Triple-negative breast cancers (TNBC) rely on other growth-promoting signals, including those from [...] Read more.
Estrogen-dependent breast cancers rely on a constant supply of estrogens and expression of estrogen receptors. Local biosynthesis, by aromatase in breast adipose fibroblasts (BAFs), is their most important source for estrogens. Triple-negative breast cancers (TNBC) rely on other growth-promoting signals, including those from the Wnt pathway. In this study, we explored the hypothesis that Wnt signaling alters the proliferation of BAFs, and is involved in regulation of aromatase expression in BAFs. Conditioned medium (CM) from TNBC cells and WNT3a consistently increased BAF growth, and reduced aromatase activity up to 90%, by suppression of the aromatase promoter I.3/II region. Database searches identified three putative Wnt-responsive elements (WREs) in the aromatase promoter I.3/II. In luciferase reporter gene assays, promoter I.3/II activity was inhibited by overexpression of full-length T-cell factor (TCF)-4 in 3T3-L1 preadipocytes, which served as a model for BAFs. Full-length lymphoid enhancer-binding factor (LEF)-1 increased the transcriptional activity. However, TCF-4 binding to WRE1 in the aromatase promoter, was lost after WNT3a stimulation in immunoprecipitation-based in vitro DNA-binding assays, and in chromatin immunoprecipitation (ChIP). In vitro DNA-binding assays, ChIP, and Western blotting revealed a WNT3a-dependent switch of nuclear LEF-1 isoforms towards a truncated variant, whereas β-catenin levels remained unchanged. This LEF-1 variant revealed dominant negative properties, and most likely recruited enzymes involved in heterochromatin formation. In addition, WNT3a induced the replacement of TCF-4 by the truncated LEF-1 variant, on WRE1 of the aromatase promoter I.3/II. The mechanism described here may be responsible for the loss of aromatase expression predominantly associated with TNBC. Tumors with (strong) expression of Wnt ligands actively suppress aromatase expression in BAFs. Consequently a reduced estrogen supply could favor the growth of estrogen-independent tumor cells, which consequently would make estrogen receptors dispensable. In summary, canonical Wnt signaling within (cancerous) breast tissue may be a major factor controlling local estrogen synthesis and action. Full article
(This article belongs to the Special Issue Prevention and Drug Treatment of Breast Cancer)
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13 pages, 4262 KiB  
Article
Expression of NUCB2/NESF-1 in Breast Cancer Cells
by Alicja Kmiecik, Katarzyna Ratajczak-Wielgomas, Jędrzej Grzegrzółka, Hanna Romanowicz, Beata Smolarz and Piotr Dziegiel
Int. J. Mol. Sci. 2022, 23(16), 9177; https://doi.org/10.3390/ijms23169177 - 16 Aug 2022
Cited by 3 | Viewed by 1557
Abstract
Recently, the expression of NUCB2/NESF-1 has been linked to tumor development. We report NUCB2/NESF-1 expression and its relation to clinicopathological parameters in breast cancer cells. Immunohistochemical reactions were conducted on 446 cases of invasive ductal carcinoma (IDC) and 36 cases of mastopathy. The [...] Read more.
Recently, the expression of NUCB2/NESF-1 has been linked to tumor development. We report NUCB2/NESF-1 expression and its relation to clinicopathological parameters in breast cancer cells. Immunohistochemical reactions were conducted on 446 cases of invasive ductal carcinoma (IDC) and 36 cases of mastopathy. The expression of NUCB2/NESF-1 was also examined at the mRNA and protein levels in breast cancer cell lines. A statistically significant higher level of NUCB2/NESF-1 in IDC cells was noted compared to that in mastopathy samples. The level of NUCB2 expression in the cytoplasm of IDC cells decreased with the increasing degree of tumor malignancy (G). Higher NUCB2 expression was found in tumors with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive phenotypes compared to that in estrogen-receptor-negative and progesterone-receptor-negative cases. Moreover, a higher expression was shown in ER(+) and PR(+) MCF-7 and T47D cell lines compared to that in triple-negative MDA-MB-468 and normal human breast epithelial cells. The analysis of the five-year survival rate indicated that a positive NUCB2/NESF-1 expression in tumor cells was also associated with longer patient survival. The study results suggest that NUCB2/NESF1 may play an important role in malignant transformation and may be a positive prognostic factor in IDC. Full article
(This article belongs to the Special Issue Prevention and Drug Treatment of Breast Cancer)
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Review

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16 pages, 2101 KiB  
Review
Function and Application of Flavonoids in the Breast Cancer
by Min Yeong Park, Yoonjung Kim, Sang Eun Ha, Hun Hwan Kim, Pritam Bhangwan Bhosale, Abuyaseer Abusaliya, Se Hyo Jeong and Gon Sup Kim
Int. J. Mol. Sci. 2022, 23(14), 7732; https://doi.org/10.3390/ijms23147732 - 13 Jul 2022
Cited by 8 | Viewed by 2330
Abstract
Breast cancer is one of the top causes of death, particularly among women, and it affects many women. Cancer can also be caused by various factors, including acquiring genetic alteration. Doctors use radiation to detect and treat breast cancer. As a result, breast [...] Read more.
Breast cancer is one of the top causes of death, particularly among women, and it affects many women. Cancer can also be caused by various factors, including acquiring genetic alteration. Doctors use radiation to detect and treat breast cancer. As a result, breast cancer becomes radiation-resistant, necessitating a new strategy for its treatment. The approach discovered by the researchers is a flavonoid, which is being researched to see if it might help treat radiation-resistant breast cancer more safely than an approved medicine already being used in the field. As a result, this study focuses on the role of flavonoids in breast cancer suppression, breast cancer gene anomalies, and the resulting apoptotic mechanism. Full article
(This article belongs to the Special Issue Prevention and Drug Treatment of Breast Cancer)
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15 pages, 1061 KiB  
Review
Breast Cancer Metastasis: Mechanisms and Therapeutic Implications
by Misung Park, Dohee Kim, Sunghyub Ko, Ayoung Kim, Kyumin Mo and Hyunho Yoon
Int. J. Mol. Sci. 2022, 23(12), 6806; https://doi.org/10.3390/ijms23126806 - 18 Jun 2022
Cited by 67 | Viewed by 8690
Abstract
Breast cancer is the most common malignancy in women worldwide. Metastasis is the leading cause of high mortality in most cancers. Although predicting the early stage of breast cancer before metastasis can increase the survival rate, breast cancer is often discovered or diagnosed [...] Read more.
Breast cancer is the most common malignancy in women worldwide. Metastasis is the leading cause of high mortality in most cancers. Although predicting the early stage of breast cancer before metastasis can increase the survival rate, breast cancer is often discovered or diagnosed after metastasis has occurred. In general, breast cancer has a poor prognosis because it starts as a local disease and can spread to lymph nodes or distant organs, contributing to a significant impediment in breast cancer treatment. Metastatic breast cancer cells acquire aggressive characteristics from the tumor microenvironment (TME) through several mechanisms including epithelial–mesenchymal transition (EMT) and epigenetic regulation. Therefore, understanding the nature and mechanism of breast cancer metastasis can facilitate the development of targeted therapeutics focused on metastasis. This review discusses the mechanisms leading to metastasis and the current therapies to improve the early diagnosis and prognosis in patients with metastatic breast cancer. Full article
(This article belongs to the Special Issue Prevention and Drug Treatment of Breast Cancer)
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