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Biomedicines
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Role of Trace Elements in Chemoprevention and Cancer Therapy
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Role of Trace Elements in Chemoprevention and Cancer Therapy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (15 May 2022) | Viewed by 21452

Special Issue Editor

Dr. Raghu Sinha

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Guest Editor
Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, PA, USA
Interests: anti-cancer mechanisms of organo-selenium compounds; cancer biomarkers; chemoprevention; cancer therapy; dietary manipulations; inflammation; systems biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Trace elements are integral to the proper functioning of several important biochemical processes in a living body. A number of essential trace elements such as iron, zinc, fluoride, selenium, copper, chromium, iodine, manganese, and molybdenum have been shown to play important roles in the etiology and prevention of chronic diseases, including cancer. Supplementation by trace elements will likely overcome deficiency-induced complications but, to better achieve cancer reduction, emerging options of using trace elements containing natural and synthetic anticancer agents such as organo-selenium or organo-zinc compounds may be employed. These anticancer agents may be used in combination with existing chemotherapy to improve survival, or as an agent to sensitize drug-resistant tumors and reduce chemotherapy-induced toxicity. Other emerging anticancer implications can include but are not limited to impact of trace elements on the tumor microenvironment, tumor hypoxia, tumor microbiota, and improvement of the immune system.

This Special Issue invites original research (in vitro and in vivo), clinical studies, and/or reviews on mechanism-driven research developments for the use of trace elements and/or trace element-containing anticancer agents in chemoprevention and cancer therapy including but not limited to the specific areas mentioned above.

Dr. Raghu Sinha
Guest Editor

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Keywords

  • trace elements
  • chromium
  • copper
  • fluoride
  • iodine
  • iron
  • manganese
  • molybdenum
  • selenium
  • zinc
  • chemoprevention
  • cancer therapy
  • combination therapy
  • drug resistance
  • immunity
  • tumor microbiota
  • tumor microenvironment
  • tumor hypoxia

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Related Special Issue

Published Papers (7 papers)

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Research

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10 pages, 10032 KiB  
Article
Selenium Induces Pancreatic Cancer Cell Death Alone and in Combination with Gemcitabine
by David J. Wooten, Indu Sinha and Raghu Sinha
Biomedicines 2022, 10(1), 149; https://doi.org/10.3390/biomedicines10010149 - 11 Jan 2022
Cited by 7 | Viewed by 2461
Abstract
Survival rate for pancreatic cancer remains poor and newer treatments are urgently required. Selenium, an essential trace element, offers protection against several cancer types and has not been explored much against pancreatic cancer specifically in combination with known chemotherapeutic agents. The present study [...] Read more.
Survival rate for pancreatic cancer remains poor and newer treatments are urgently required. Selenium, an essential trace element, offers protection against several cancer types and has not been explored much against pancreatic cancer specifically in combination with known chemotherapeutic agents. The present study was designed to investigate selenium and Gemcitabine at varying doses alone and in combination in established pancreatic cancer cell lines growing in 2D as well as 3D platforms. Comparison of multi-dimensional synergy of combinations’ (MuSyc) model and highest single agent (HSA) model provided quantitative insights into how much better the combination performed than either compound tested alone in a 2D versus 3D growth of pancreatic cancer cell lines. The outcomes of the study further showed promise in combining selenium and Gemcitabine when evaluated for apoptosis, proliferation, and ENT1 protein expression, specifically in BxPC-3 pancreatic cancer cells in vitro. Full article
(This article belongs to the Special Issue Role of Trace Elements in Chemoprevention and Cancer Therapy)
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11 pages, 588 KiB  
Article
Pre-Clinical Insights into the Iron and Breast Cancer Hypothesis
by Henry J. Thompson, Elizabeth S. Neil and John N. McGinley
Biomedicines 2021, 9(11), 1652; https://doi.org/10.3390/biomedicines9111652 - 9 Nov 2021
Cited by 5 | Viewed by 2323
Abstract
Population studies, systematic reviews, and meta-analyses have revealed no relationship between iron status and breast cancer, a weak positive association, or a small protective effect of low iron status. However, in those studies, the authors concluded that further investigation was merited. The set [...] Read more.
Population studies, systematic reviews, and meta-analyses have revealed no relationship between iron status and breast cancer, a weak positive association, or a small protective effect of low iron status. However, in those studies, the authors concluded that further investigation was merited. The set of experiments reported here used preclinical models to assess the likely value of further investigation. The effects of iron status on the initiation and promotion stage of mammary carcinogenesis are reported. Using the classical model of cancer initiation in the mammary gland, 7,12 dimethyl-benz[α]anthracene-induced carcinogenesis was unaffected by iron status. Similarly, excess iron intake showed no effect on the promotion stage of 1-methyl-1-nitrosurea-induced mammary carcinogenesis, though iron deficiency exerted a specific inhibitory effect on the carcinogenic process. Though iron-mediated cellular oxidation is frequently cited as a potential mechanism for effects on breast cancer, no evidence of increased oxidative damage to DNA attributable to excess iron intake was found. The reported preclinical data fail to provide convincing evidence that the further evaluation of the iron–breast cancer risk hypotheses is warranted and underscore the value of redefining the referent group in population-based studies of iron–cancer hypotheses in other tissues. Full article
(This article belongs to the Special Issue Role of Trace Elements in Chemoprevention and Cancer Therapy)
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10 pages, 275 KiB  
Article
Blood Copper Levels and the Occurrence of Colorectal Cancer in Poland
by Piotr Baszuk, Wojciech Marciniak, Róża Derkacz, Anna Jakubowska, Cezary Cybulski, Jacek Gronwald, Tadeusz Dębniak, Tomasz Huzarski, Katarzyna Białkowska, Sandra Pietrzak, Magdalena Muszyńska, Józef Kładny, Steven A. Narod, Jan Lubiński and Marcin R. Lener
Biomedicines 2021, 9(11), 1628; https://doi.org/10.3390/biomedicines9111628 - 5 Nov 2021
Cited by 27 | Viewed by 2451
Abstract
There is a need for sensitive and specific biomarkers for the early detection of colorectal cancer. In this retrospective study, we assessed whether a high blood copper level was associated with the presence of colorectal cancer. The blood copper level was measured among [...] Read more.
There is a need for sensitive and specific biomarkers for the early detection of colorectal cancer. In this retrospective study, we assessed whether a high blood copper level was associated with the presence of colorectal cancer. The blood copper level was measured among 187 colorectal cancer patients and 187 matched controls. Cases and controls were matched for sex, smoking status (yes/no) and year of birth. Among the cases, the mean blood copper level was 1031 µg/L (range 657 µg/L to 2043 µg/L) and among the controls, the mean blood copper level was 864 µg/L (range 589 µg/L to 1433 µg/L). The odds ratio for colorectal cancer for those in the highest quartile of copper level (versus the lowest) was 12.7 (95% CI: 4.98–32.3; p < 0.001). Of the patients with stage I–II colon cancer, 62% had a copper level in the highest quartile. A blood copper level in excess of 930 µg/L is associated with an increase in the prevalence of colorectal cancer in the Polish population and its potential use in early detection programs should be considered. Full article
(This article belongs to the Special Issue Role of Trace Elements in Chemoprevention and Cancer Therapy)
15 pages, 325 KiB  
Article
Prediagnostic Blood Selenium Status and Mortality among Patients with Colorectal Cancer in Western European Populations
by Jacqueline Roshelli Baker, Sushma Umesh, Mazda Jenab, Lutz Schomburg, Anne Tjønneland, Anja Olsen, Marie-Christine Boutron-Ruault, Joseph A. Rothwell, Gianluca Severi, Verena Katzke, Theron Johnson, Matthias B. Schulze, Giovanna Masala, Claudia Agnoli, Vittorio Simeon, Rosario Tumino, H. Bas Bueno-de-Mesquita, Inger Torhild Gram, Guri Skeie, Catalina Bonet, Miguel Rodriguez-Barranco, José María Houerta, Björn Gylling, Bethany Van Guelpen, Aurora Perez-Cornago, Elom Aglago, Heinz Freisling, Elisabete Weiderpass, Amanda J. Cross, Alicia K. Heath, David J. Hughes and Veronika Fedirkoadd Show full author list remove Hide full author list
Biomedicines 2021, 9(11), 1521; https://doi.org/10.3390/biomedicines9111521 - 22 Oct 2021
Cited by 13 | Viewed by 3256
Abstract
A higher selenium (Se) status has been shown to be associated with lower risk for colorectal cancer (CRC), but the importance of Se in survival after CRC diagnosis is not well studied. The associations of prediagnostic circulating Se status (as indicated by serum [...] Read more.
A higher selenium (Se) status has been shown to be associated with lower risk for colorectal cancer (CRC), but the importance of Se in survival after CRC diagnosis is not well studied. The associations of prediagnostic circulating Se status (as indicated by serum Se and selenoprotein P (SELENOP) measurements) with overall and CRC-specific mortality were estimated using multivariable Cox proportional hazards regression among 995 CRC cases (515 deaths, 396 from CRC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Se and SELENOP serum concentrations were measured on average 46 months before CRC diagnosis. Median follow-up time was 113 months. Participants with Se concentrations in the highest quintile (≥100 µg/L) had a multivariable-adjusted hazard ratio (HR) of 0.73 (95% CI: 0.52–1.02; Ptrend = 0.06) for CRC-specific mortality and 0.77 (95% CI: 0.57–1.03; Ptrend = 0.04) for overall mortality, compared with the lowest quintile (≤67.5 µg/L). Similarly, participants with SELENOP concentrations in the highest (≥5.07 mg/L) compared with the lowest quintile (≤3.53 mg/L) had HRs of 0.89 (95% CI: 0.64–1.24; Ptrend = 0.39) for CRC-specific mortality and 0.83 (95% CI: 0.62–1.11; Ptrend = 0.17) for overall mortality. Higher prediagnostic exposure to Se within an optimal concentration (100–150 µg/L) might be associated with improved survival among CRC patients, although our results were not statistically significant and additional studies are needed to confirm this potential association. Our findings may stimulate further research on selenium’s role in survival among CRC patients especially among those residing in geographic regions with suboptimal Se availability. Full article
(This article belongs to the Special Issue Role of Trace Elements in Chemoprevention and Cancer Therapy)
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9 pages, 283 KiB  
Communication
Low Blood-As Levels and Selected Genotypes Appears to Be Promising Biomarkers for Occurrence of Colorectal Cancer in Women
by Piotr Baszuk, Paulina Stadnik, Wojciech Marciniak, Róża Derkacz, Anna Jakubowska, Cezary Cybulski, Tomasz Huzarski, Jacek Gronwald, Tadeusz Dębniak, Katarzyna Białkowska, Sandra Pietrzak, Józef Kładny, Rodney J. Scott, Jan Lubiński and Marcin R. Lener
Biomedicines 2021, 9(9), 1105; https://doi.org/10.3390/biomedicines9091105 - 28 Aug 2021
Viewed by 2264
Abstract
In following study we examined whether blood arsenic (As) levels combined with specific polymorphisms in MT1B, GSTP1, ABCB1, NQO1, CRTC3, GPX1, SOD2, CAT, XRCC1, ERCC2 can be used as a marker for the detection [...] Read more.
In following study we examined whether blood arsenic (As) levels combined with specific polymorphisms in MT1B, GSTP1, ABCB1, NQO1, CRTC3, GPX1, SOD2, CAT, XRCC1, ERCC2 can be used as a marker for the detection of colorectal cancer (CRC) among Polish women. A retrospective case-control study of CRC included 83 CRC cases and 78 healthy controls. From each study participant pre-treatment peripheral blood was collected for As level measurement by inductively coupled–plasma mass spectrometry (ICP-MS). We estimated the odds ratio (OR) of the association between blood-As levels and CRC using multivariable unconditional logistic regression models. A low blood-As level (0.27–0.67 µg/L) was associated with an increased frequency of CRC (OR: 3.69; p = 0.005). This correlation was significantly greater when participants carried particular gene variants: CAT, rs1001179-nonCC (OR: 19.4; p = 0.001); ABCB1 rs2032582–CC (OR: 14.8; p = 0.024); GPX1 rs1050450-CC (OR: 11.6; p = 0.002) and CRTC3 rs12915189-nonGG (OR: 10.3; p = 0.003). Our study provides strong evidence that low blood-As levels are significantly associated with increased CRC occurrence and that particular gene variants significantly enhanced this correlation however, due to the novelty of these findings, we suggest further validation before a definitive statement that the combined effect of low blood-As levels with specific gene polymorphisms is a suitable CRC biomarker. Full article
(This article belongs to the Special Issue Role of Trace Elements in Chemoprevention and Cancer Therapy)
8 pages, 541 KiB  
Communication
Serum Selenium Level and 10-Year Survival after Melanoma
by Emilia Rogoża-Janiszewska, Karolina Malińska, Piotr Baszuk, Wojciech Marciniak, Róża Derkacz, Marcin Lener, Anna Jakubowska, Cezary Cybulski, Tomasz Huzarski, Bartłomiej Masojć, Jacek Gronwald, Helena Rudnicka, Andrzej Kram, Magdalena Kiedrowicz, Magdalena Boer, Tadeusz Dębniak and Jan Lubiński
Biomedicines 2021, 9(8), 991; https://doi.org/10.3390/biomedicines9080991 - 11 Aug 2021
Cited by 14 | Viewed by 2959
Abstract
Melanoma is one of the most aggressive human malignancies. The determination of prognostic biomarkers is important for the early detection of recurrence and for the enrollment of the patients into different treatment regimens. Herein, we report the 10-year survival of 375 melanoma patients [...] Read more.
Melanoma is one of the most aggressive human malignancies. The determination of prognostic biomarkers is important for the early detection of recurrence and for the enrollment of the patients into different treatment regimens. Herein, we report the 10-year survival of 375 melanoma patients depending on their serum selenium levels. The study group was followed up from the date of melanoma diagnosis until death or 2020. Patients were assigned to one of four categories, in accordance with the increasing selenium level (I–IV quartiles). The subgroup with low selenium levels had a significant lower survival rate in relation to patients with high selenium levels, HR = 8.42; p = 0.005 and HR = 5.83; p = 0.02, for uni- and multivariable models, respectively. In the univariable analysis, we also confirmed the association between Breslow thickness, Clark classification and age at melanoma prognosis. In conclusion, a low serum selenium level was associated with an increased mortality rate in the 10 years following melanoma diagnosis. Future studies in other geographic regions with low soil selenium levels should be conducted to confirm our findings. Full article
(This article belongs to the Special Issue Role of Trace Elements in Chemoprevention and Cancer Therapy)
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Review

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17 pages, 877 KiB  
Review
Zinc Signaling in the Mammary Gland: For Better and for Worse
by Moumita Chakraborty and Michal Hershfinkel
Biomedicines 2021, 9(9), 1204; https://doi.org/10.3390/biomedicines9091204 - 12 Sep 2021
Cited by 6 | Viewed by 3577
Abstract
Zinc (Zn2+) plays an essential role in epithelial physiology. Among its many effects, most prominent is its action to accelerate cell proliferation, thereby modulating wound healing. It also mediates affects in the gastrointestinal system, in the testes, and in secretory organs, [...] Read more.
Zinc (Zn2+) plays an essential role in epithelial physiology. Among its many effects, most prominent is its action to accelerate cell proliferation, thereby modulating wound healing. It also mediates affects in the gastrointestinal system, in the testes, and in secretory organs, including the pancreas, salivary, and prostate glands. On the cellular level, Zn2+ is involved in protein folding, DNA, and RNA synthesis, and in the function of numerous enzymes. In the mammary gland, Zn2+ accumulation in maternal milk is essential for supporting infant growth during the neonatal period. Importantly, Zn2+ signaling also has direct roles in controlling mammary gland development or, alternatively, involution. During breast cancer progression, accumulation or redistribution of Zn2+ occurs in the mammary gland, with aberrant Zn2+ signaling observed in the malignant cells. Here, we review the current understanding of the role of in Zn2+ the mammary gland, and the proteins controlling cellular Zn2+ homeostasis and signaling, including Zn2+ transporters and the Gq-coupled Zn2+ sensing receptor, ZnR/GPR39. Significant advances in our understanding of Zn2+ signaling in the normal mammary gland as well as in the context of breast cancer provides new avenues for identification of specific targets for breast cancer therapy. Full article
(This article belongs to the Special Issue Role of Trace Elements in Chemoprevention and Cancer Therapy)
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