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Natural Chemotherapeutic Compounds for Prevention and Treatment of Breast Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 November 2021) | Viewed by 4737

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)
Special Issues, Collections and Topics in MDPI journals

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 use of natural chemotherapeutic compounds for the prevention and/or treatment of breast cancer. In addition, this Special Issue will address the issues of preventive measures for breast cancer.

Dr. Clement G. Yedjou
Guest Editor

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Keywords

  • breast cancer
  • conventional therapy
  • traditional medicine
  • natural product
  • prevention
  • treatment

Published Papers (2 papers)

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Research

16 pages, 8046 KiB  
Article
Investigation of NPB Analogs That Target Phosphorylation of BAD-Ser99 in Human Mammary Carcinoma Cells
by Swamy Savvemala Girimanchanaika, Dukanya Dukanya, Ananda Swamynayaka, Divya Maldepalli Govindachar, Mahendra Madegowda, Ganga Periyasamy, Kanchugarakoppal Subbegowda Rangappa, Vijay Pandey, Peter E. Lobie and Basappa Basappa
Int. J. Mol. Sci. 2021, 22(20), 11002; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222011002 - 12 Oct 2021
Cited by 1 | Viewed by 1704
Abstract
The design and development of a small molecule named NPB [3-{(4(2,3-dichlorophenyl)piperazin-1-yl}{2-hydroxyphenyl)methyl}-N-cyclopentylbenzamide], which specifically inhibited the phosphorylation of BAD at Ser99 in human carcinoma cells has been previously reported. Herein, the synthesis, characterization, and effect on cancer cell viability of NPB analogs, and the [...] Read more.
The design and development of a small molecule named NPB [3-{(4(2,3-dichlorophenyl)piperazin-1-yl}{2-hydroxyphenyl)methyl}-N-cyclopentylbenzamide], which specifically inhibited the phosphorylation of BAD at Ser99 in human carcinoma cells has been previously reported. Herein, the synthesis, characterization, and effect on cancer cell viability of NPB analogs, and the single-crystal X-ray crystallographic studies of an example compound (4r), which was grown via slow-solvent evaporation technique is reported. Screening for loss of viability in mammary carcinoma cells revealed that compounds such as 2[(4(2,3-dichlorophenyl)piperazin-1-yl][naphthalen-1-yl]methyl)phenol (4e), 5[(4(2,3-dichlorophenyl)piperazin-1-yl][2-hydroxyphenyl)methyl)uran-2-carbaldehyde (4f), 3[(2-hydroxyphenyl][4(p-tolyl)piperazin-1-yl)methyl)benzaldehyde (4i), and NPB inhibited the viability of MCF-7 cells with IC50 values of 5.90, 3.11, 7.68, and 6.5 µM, respectively. The loss of cell viability was enhanced by the NPB analogs synthesized by adding newer rings such as naphthalene and furan-2-carbaldehyde in place of N-cyclopentyl-benzamide of NPB. Furthermore, these compounds decreased Ser99 phosphorylation of hBAD. Additional in silico density functional theory calculations suggested possibilities for other analogs of NPB that may be more suitable for further development. Full article
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17 pages, 2720 KiB  
Article
Cumin Prevents 17β-Estradiol-Associated Breast Cancer in ACI Rats
by Farrukh Aqil, Jeyaprakash Jeyabalan, Radha Munagala, Iqbal Ahmad, David J. Schultz and Ramesh C. Gupta
Int. J. Mol. Sci. 2021, 22(12), 6194; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126194 - 08 Jun 2021
Cited by 3 | Viewed by 2399
Abstract
Breast cancer (BC) is a leading cause of cancer deaths in women in less developed countries and the second leading cause of cancer death in women in the U.S. In this study, we report the inhibition of E2-mediated mammary tumorigenesis by Cuminum cyminum [...] Read more.
Breast cancer (BC) is a leading cause of cancer deaths in women in less developed countries and the second leading cause of cancer death in women in the U.S. In this study, we report the inhibition of E2-mediated mammary tumorigenesis by Cuminum cyminum (cumin) administered via the diet as cumin powder, as well as dried ethanolic extract. Groups of female ACI rats were given either an AIN-93M diet or a diet supplemented with cumin powder (5% and 7.5%, w/w) or dried ethanolic cumin extract (1%, w/w), and then challenged with subcutaneous E2 silastic implants (1.2 cm; 9 mg). The first appearance of a palpable mammary tumor was significantly delayed by both the cumin powder and extract. At the end of the study, the tumor incidence was 96% in the control group, whereas only 55% and 45% animals had palpable tumors in the cumin powder and extract groups, respectively. Significant reductions in tumor volume (660 ± 122 vs. 138 ± 49 and 75 ± 46 mm3) and tumor multiplicity (4.21 ± 0.43 vs. 1.16 ± 0.26 and 0.9 ± 0.29 tumors/animal) were also observed by the cumin powder and cumin extract groups, respectively. The cumin powder diet intervention dose- and time-dependently offset E2-related pituitary growth, and reduced the levels of circulating prolactin and the levels of PCNA in the mammary tissues. Mechanistically, the cumin powder diet resulted in a significant reversal of E2-associated modulation in ERα, CYP1A1 and CYP1B1. Further, the cumin powder diet reversed the expression levels of miRNAs (miR-182, miR-375, miR-127 and miR-206) that were highly modulated by E2 treatment. We analyzed the composition of the extract by GC/MS and established cymene and cuminaldehyde as major components, and further detected no signs of gross or systemic toxicity. Thus, cumin bioactives can significantly delay and prevent E2-mediated mammary tumorigenesis in a safe and effective manner, and warrant continued efforts to develop these clinically translatable spice bioactives as chemopreventives and therapeutics against BC. Full article
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