Role of natural products in breast cancer related symptomology: Targeting chronic inflammation

doi:10.1016/j.semcancer.2020.08.011

Seminars in Cancer Biology

Volume 80, May 2022, Pages 370-378

https://doi.org/10.1016/j.semcancer.2020.08.011 Get rights and content

Abstract

Breast cancer is the most common cancer in women worldwide. There have been many advancements in the treatment of breast cancer leading to an increased population of patients living with this disease. Accumulating evidence suggests that cancer diagnosis and aftermath experienced stress could not only affect the quality of life of cancer patients, but it could also influence their disease outcome. The magnitude of stress experienced by breast cancer patients is often compared to the post-traumatic stress disorder-like symptoms suggested to be mediated by the chronic inflammation including NF-κB, AKt, p53 and other inflammatory pathways. Here, we describe the symptomology of PTSD-like symptoms in breast cancer patients and argue that they may in fact be caused by or maintained through aspects of chronic inflammation mediated by the pro-inflammatory markers. Evidence exists that natural products that might attenuate or lessen the effects of chronic inflammation abound in the diet. We summarize some possible agents that might abate the genesis of symptoms experienced by breast cancer patients while mitigating the effect of inflammation.

Section snippets

Prevalence of psychological-stress related symptoms

Breast cancer (BC) is the second most commonly diagnosed cancer in women in the United States and a prime reason for death in women globally [1]. Due to advances in medical treatment, breast cancer mortality rates have decreased in recent years, leading to more individuals living with cancer. At present, there are 3.1 million women in the US with a history of breast cancer including women currently being treated and women who have finished their treatment [2]. This suggests that there is a huge

Links of PTSD-like symptoms in BC to chronic inflammation

Physiological and behavioral changes in the body are being coordinated by several systems including the immune, the endocrine, and the central and peripheral systems that constantly communicate with each other [24]. Given PTSD is a disorder of the stress response, it results in the hypothalamic-pituitary-adrenal axis (HPA) reactivity, activation of the immune system, and the release of the stress hormones and the production of pro-inflammatory cytokines and other neurotoxins. With continuous

Natural products as interventions to alleviate PTSD-like symptoms

Given the evidence that a pro-inflammatory state could dictate the length and severity of post-cancer symptoms, consumption of anti-inflammatory (AI) foods benefit BC patients and survivors in several ways. Findings from the Women's Health Initiative suggested that the adoption of AI foods in the post-cancer diagnosis diet benefitted women by reducing the risk for future cardiovascular disease [85]. In the same cohort, the consumption of AI food and supplements resulted in improved survival for

Conclusions and future directions of natural products in breast cancer related symptomology

Based on the findings derived from different studies, our review demonstrates a strong link between PTSD-like symptoms and chronic inflammation in breast cancer patients. Due to severe side effects and multidrug resistance, BC treatment approaches becoming not that effective. Natural products and dietary compounds are reported to have multiple anti-cancer properties and are often considered as attractive novel treatment strategies for targeting chronic inflammation.

Many of the PTSD-like

Funding

UT Health San Antonio Mays Cancer Center.

Declaration of Competing Interest

The authors report no declarations of interest.

Acknowledgements

We would like to thank Dr. Jay Morris for his insights and suggestions.

References (170)

W. Linden
Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age
J. Affect. Disord.
(2012)
M.J. Cordova et al.
Post-traumatic stress disorder and cancer
Lancet Psychiatry
(2017)
E.A. Mundy
Posttraumatic stress disorder in breast cancer patients following autologous bone marrow transplantation or conventional cancer treatments
Behav. Res. Ther.
(2000)
T.W. Pace et al.
A short review on the psychoneuroimmunology of posttraumatic stress disorder: from risk factors to medical comorbidities
Brain Behav. Immun.
(2011)
S. Suman
Current perspectives of molecular pathways involved in chronic inflammation-mediated breast cancer
Biochem. Biophys. Res. Commun.
(2016)
D. Tewari
Targeting activator protein 1 signaling pathway by bioactive natural agents: possible therapeutic strategy for cancer prevention and intervention
Pharmacol. Res.
(2018)
C. Wang
Triple negative breast cancer in Asia: an insider’s view
Cancer Treat. Rev.
(2018)
T.J. Hartung
The risk of being depressed is significantly higher in cancer patients than in the general population: prevalence and severity of depressive symptoms across major cancer types
Eur. J. Cancer
(2017)
K. Young et al.
Biological mechanisms of cancer-induced depression
Front. Psychiatry
(2018)
H. Soygur
Interleukin-6 levels and HPA axis activation in breast cancer patients with major depressive disorder
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2007)

B. Bortolato

Depression in cancer: the many biobehavioral pathways driving tumor progression

Cancer Treat. Rev.

(2017)

W.A. Bardwell et al.

Breast cancer and fatigue

Sleep Med. Clin.

(2008)

K.A. Donovan

Course of fatigue in women receiving chemotherapy and/or radiotherapy for early stage breast cancer

J. Pain Symptom Manage.

(2004)

P.J. Mills

The relationship between fatigue and quality of life and inflammation during anthracycline-based chemotherapy in breast cancer

Biol. Psychol.

(2005)

L. Pusztai

Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy

Cytokine

(2004)

J.E. Bower

Fatigue and gene expression in human leukocytes: increased NF-kappaB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue

Brain Behav. Immun.

(2011)

M.E. Schmidt

Cancer-related fatigue shows a stable association with diurnal cortisol dysregulation in breast cancer patients

Brain Behav. Immun.

(2016)

H.K. Meier-Ewert

Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk

J. Am. Coll. Cardiol.

(2004)

W.T. Shearer

Soluble TNF-alpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight

J. Allergy Clin. Immunol.

(2001)

M.R. Irwin

Sleep loss activates cellular inflammatory signaling

Biol. Psychiatry

(2008)

Y. Yang et al.

Cancer-related cognitive impairment in breast cancer patients: influences of psychological variables

Asia. J. Oncol. Nurs.

(2018)

M.C. Janelsins

An update on cancer- and chemotherapy-related cognitive dysfunction: current status

Semin. Oncol.

(2011)

Y.T. Cheung

Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study

Ann. Oncol.

(2015)

A.M. Williams

Associations between inflammatory markers and cognitive function in breast cancer patients receiving chemotherapy

J. Neuroimmunol.

(2018)

L.R. Watkins

Characterization of cytokine-induced hyperalgesia

Brain Res.

(1994)

P. Ungprasert

Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury: a systematic review and meta-analysis of observational studies

Eur. J. Intern. Med.

(2015)

J.C. Yi et al.

Anxiety and depression in Cancer survivors

Med. Clin. North Am.

(2017)

Prevention, C.f.D.C.a., Breast...

B.C. Org

U.S. Breast Cancer Statistics

(2019)

P.H. Thaker

Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma

Nat. Med.

(2006)

A. Reeder

Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage

Br. J. Cancer

(2015)

S.K. Lutgendorf

Biobehavioral influences on matrix metalloproteinase expression in ovarian carcinoma

Clin. Cancer Res.

(2008)

M.M.S. Obradovic

Glucocorticoids promote breast cancer metastasis

Nature

(2019)

Y. Chida

Do stress-related psychosocial factors contribute to cancer incidence and survival?

Nat. Clin. Pract. Oncol.

(2008)

M. Pinquart et al.

Depression and cancer mortality: a meta-analysis

Psychol. Med.

(2010)

N.C. Institute

Cancer-Related Post-traumatic Stress (PDQ(R)): Health Professional Version, in PDQ Cancer Information Summaries

(2002)

M.A. Andrykowski

Stability and change in posttraumatic stress disorder symptoms following breast cancer treatment: a 1-year follow-up

Psychooncology

(2000)

M.J. Cordova

Frequency and correlates of posttraumatic-stress-disorder-like symptoms after treatment for breast cancer

J. Consult. Clin. Psychol.

(1995)

A.P. Association

Diagnostic and Statistical Manual of Mental Disorders

(2013)

M.A. Andrykowski

Posttraumatic stress disorder after treatment for breast cancer: prevalence of diagnosis and use of the PTSD Checklist-Civilian Version (PCL-C) as a screening instrument

J. Consult. Clin. Psychol.

(1998)

A. Mehnert et al.

Prevalence of acute and post-traumatic stress disorder and comorbid mental disorders in breast cancer patients during primary cancer care: a prospective study

Psychooncology

(2007)

V. Voigt

Clinically assessed posttraumatic stress in patients with breast cancer during the first year after diagnosis in the prospective, longitudinal, controlled COGNICARES study

Psychooncology

(2017)

M. Kangas et al.

Predictors of posttraumatic stress disorder following cancer

Health Psychol.

(2005)

D. Spiegel et al.

Managing anxiety and depression during treatment

Breast J.

(2015)

C.R. Figley

Stress Disorders Among Vietnam Veterans

(1978)

A. Pai et al.

Posttraumatic stress disorder in the DSM-5: controversy, change, and conceptual considerations

Behav. Sci. (Basel)

(2017)

X. Wu

Prevalence of posttraumatic stress disorder among breast cancer patients: a meta-analysis

Iran. J. Public Health

(2016)

B.A. Murphy

Chronic systemic symptoms in head and neck cancer patients

J. Natl. Cancer Inst. Monogr.

(2019)

V. Michopoulos

Inflammation in fear- and anxiety-based disorders: PTSD, GAD, and beyond

Neuropsychopharmacology

(2017)

N. Rohleder

Stimulation of systemic low-grade inflammation by psychosocial stress

Psychosom. Med.

(2014)

Cited by (19)

Natural products and derivatives for breast cancer treatment: From drug discovery to molecular mechanism
2024, Phytomedicine
Breast cancer stands as the most common malignancy among women globally and a leading cause of cancer-related mortality. Conventional treatments, such as surgery, hormone therapy, radiotherapy, chemotherapy, and small-molecule targeted therapy, often fall short of addressing the complexity and heterogeneity of certain breast cancer subtypes, leading to drug resistance and metastatic progression. Thus, the search for novel therapeutic targets and agents is imperative. Given their low toxicity and abundant variety, natural products and their derivatives are increasingly considered valuable sources for small-molecule anticancer drugs.
This review aims to elucidate the pharmacological impacts and underlying mechanisms of active compounds found in select natural products and their derivatives, primarily focusing on breast cancer treatment. It intends to underscore the potential of these substances in combating breast cancer and guide future research directions for the development of natural product-based therapeutics.
We conducted comprehensive searches in electronic databases such as PubMed, Web of Science, and Scopus until October 2023, using keywords such as 'breast cancer', 'natural products', 'derivatives', 'mechanism', 'signaling pathways', and various keyword combinations.
The review presents a spectrum of phytochemicals, including but not limited to flavonoids, polyphenols, and alkaloids, and examines their actions in various animal and cellular models of breast cancer. The anticancer effects of these natural products and derivatives are manifested through diverse mechanisms, including induction of cell death via apoptosis and autophagy, and suppression of tumor angiogenesis.
An increasing array of natural products and their derivatives are proving effective against breast cancer. Future therapeutic strategies can benefit from strategic enhancement of the anticancer properties of natural compounds, optimization for targeted action, improved bioavailability, and minimized side effects. The forthcoming research on natural products should prioritize these facets to maximize their therapeutic potential
Nanoformulations of curcumin: An alliance for effective cancer therapeutics
2023, Food Bioscience
Cancer is intimidating in its diversity, genetics, epigenetics, pathology, diagnosis, and response to therapy. The high rate of recurrence and development of resistance to therapies hinder the prognosis and the inadvertent side effects of contemporary medications can reduce the quality of life in patients. These observations emphasize the need for multi-targeted treatments that are not only relatively safe and economical, but also provide a more effective alternative to the conventional treatment modalities. Over the last few decades, scientific data has demonstrated that curcumin has a wide range of anti-cancer effects that are orchestrated via affecting diverse cancer signaling pathways. Nonetheless, the therapeutic applicability of curcumin is severely limited due to its low water solubility, poor oral absorption, and rapid clearance. These limitations prompted the development of various curcumin formulations including nanotechnology based delivery systems for the prevention and treatment of cancers. Therefore, we aimed to review the potential benefits of nanocurcumin in treating various cancer. We conducted a comprehensive search on the PubMed database to identify relevant publications concerning the use of nanocurcumin in cancer treatment, utilizing the search term 'nanocurcumin and cancer'. This review summarizes various preclinical and clinical studies that highlight the anticancer activities of curcumin nanoformulations including cyclodextrin complexes, dendrimers, exosomes, liposomes, gold nanoparticles (NPs), graphene nanocomposites, magnetic NPs, micelles, nanogels, polymeric NPs and solid-lipid NPs (SLNs). We further presented cellular mechanisms and clinical investigations, thus, emphasizing its potential in cancer prevention and treatment or even as an adjuvant therapy with conventional drugs to enhance therapeutic results in cancer patients.
How far have we explored fungi to fight cancer?
2022, Seminars in Cancer Biology
Citation Excerpt :
Anticancer drug discovery from natural products has been ongoing for decades [1–4].
The use of fungal cultures have been well documented in human history. Although its used in healthcare, like penicillin and statins, have saved countless of lives, but there is still no fungal products that are specifically indicated for cancers. Research into fungal-derived materials to curb cancers in the recent decades have made a considerable progress in terms of drug delivery vehicles, anticancer active ingredients and cancer immunotherapy. Various parts of the organisms have successfully been exploited to achieve specific tasks. Apart from the identification of novel anticancer compound from fungi, its native capsular structure can also be used as drug cargo to achieve higher oral bioavailability. This review summarises the anticancer potential of fungal-derived materials, highlighting the role of capsular polysaccharides, proteins, and other structures in variety of innovative utilities to fit the current pharmaceutical technology. Many bioactive compounds isolated from fungi have also been formulated into nanoparticles to achieve greater anticancer activity. The progress of fungal compounds and their analogues in clinical trials is also highlighted. In addition, the potential of various fungal species to be developed for anticancer immunotherapy are also discussed.
Exosomes deliver lncRNA DARS-AS1 siRNA to inhibit chronic unpredictable mild stress-induced TNBC metastasis
2022, Cancer Letters
Citation Excerpt :
In addition, DARS-AS1 overexpression markedly enhanced TNBC tumorigenesis and metastasis by targeting miR-129-2-3p to upregulate CDK1 both in vitro and in vivo, and silencing DARS-AS1 or its downstream target gene, CDK1, suppressed TNBC development. The NF-κB/STAT3 axis is a well-known stress-related signaling pathway [42,43] that is activated in various malignancies. Ginsenoside Rh1 suppressed the metastasis of MDA-MB-231 cells by inactivating STAT3/NF-κB signaling [44].
Triple-negative breast cancer (TNBC) is a rapidly recurring and highly metastatic malignancy with high heterogeneity and chemoradiotherapy resistance. Chronic unpredictable mild stress (CUMS) can induce the occurrence of tumors and enhance lymphatic infiltration and distant metastasis through direct interaction with the sympathetic nervous system; however, its relevance in TNBC is yet to be clarified. In this study, DARS-AS1, a newly reported CUMS-responsive lncRNA, was found to be enriched in TNBC clinical tumors and cells and positively correlated with late clinical stage in patients with TNBC. DARS-AS1 overexpression significantly enhanced the migration and invasion of TNBC tumors by inhibiting miR-129-2-3p and upregulated CDK1 to activate the NF-κB/STAT3 signaling pathway both in vitro and in vivo. Treatment with DARS-AS1 siRNA-loaded exosomes (EXOs) substantially slowed CUMS-induced TNBC cell growth and liver metastasis. Therefore, DARS-AS1 represents a potential therapeutic target for metastatic TNBC, and EXOs may serve as siRNA delivery carriers in clinical therapy.
Safe Induction of Acute Inflammation with Enhanced Antitumor Immunity by Hydrogel-Mediated Outer Membrane Vesicle Delivery
2024, Small Methods
Molecular Pathways of Rosmarinic Acid Anticancer Activity in Triple-Negative Breast Cancer Cells: A Literature Review
2024, Nutrients

View all citing articles on Scopus

View full text

ReviewRole of natural products in breast cancer related symptomology: Targeting chronic inflammation

Abstract

Section snippets

Prevalence of psychological-stress related symptoms

Links of PTSD-like symptoms in BC to chronic inflammation

Natural products as interventions to alleviate PTSD-like symptoms

Conclusions and future directions of natural products in breast cancer related symptomology

Funding

Declaration of Competing Interest

Acknowledgements

J. Affect. Disord.

Lancet Psychiatry

Behav. Res. Ther.

Brain Behav. Immun.

Biochem. Biophys. Res. Commun.

Pharmacol. Res.

Cancer Treat. Rev.

Eur. J. Cancer

Front. Psychiatry

Prog. Neuropsychopharmacol. Biol. Psychiatry

Cancer Treat. Rev.

Sleep Med. Clin.

J. Pain Symptom Manage.

Biol. Psychol.

Cytokine

Brain Behav. Immun.

Brain Behav. Immun.

J. Am. Coll. Cardiol.

J. Allergy Clin. Immunol.

Biol. Psychiatry

Asia. J. Oncol. Nurs.

Semin. Oncol.

Ann. Oncol.

J. Neuroimmunol.

Brain Res.

Eur. J. Intern. Med.

Med. Clin. North Am.

U.S. Breast Cancer Statistics

Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma

Nat. Med.

Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage

Br. J. Cancer

Biobehavioral influences on matrix metalloproteinase expression in ovarian carcinoma

Clin. Cancer Res.

Glucocorticoids promote breast cancer metastasis

Nature

Do stress-related psychosocial factors contribute to cancer incidence and survival?

Nat. Clin. Pract. Oncol.

Depression and cancer mortality: a meta-analysis

Psychol. Med.

Cancer-Related Post-traumatic Stress (PDQ(R)): Health Professional Version, in PDQ Cancer Information Summaries

Stability and change in posttraumatic stress disorder symptoms following breast cancer treatment: a 1-year follow-up

Psychooncology

Frequency and correlates of posttraumatic-stress-disorder-like symptoms after treatment for breast cancer

J. Consult. Clin. Psychol.

Diagnostic and Statistical Manual of Mental Disorders

Posttraumatic stress disorder after treatment for breast cancer: prevalence of diagnosis and use of the PTSD Checklist-Civilian Version (PCL-C) as a screening instrument

J. Consult. Clin. Psychol.

Prevalence of acute and post-traumatic stress disorder and comorbid mental disorders in breast cancer patients during primary cancer care: a prospective study

Psychooncology

Clinically assessed posttraumatic stress in patients with breast cancer during the first year after diagnosis in the prospective, longitudinal, controlled COGNICARES study

Psychooncology

Predictors of posttraumatic stress disorder following cancer

Health Psychol.

Managing anxiety and depression during treatment

Breast J.

Stress Disorders Among Vietnam Veterans

Posttraumatic stress disorder in the DSM-5: controversy, change, and conceptual considerations

Behav. Sci. (Basel)

Prevalence of posttraumatic stress disorder among breast cancer patients: a meta-analysis

Iran. J. Public Health

Chronic systemic symptoms in head and neck cancer patients

J. Natl. Cancer Inst. Monogr.

Inflammation in fear- and anxiety-based disorders: PTSD, GAD, and beyond

Neuropsychopharmacology

Stimulation of systemic low-grade inflammation by psychosocial stress

Psychosom. Med.

Review
Role of natural products in breast cancer related symptomology: Targeting chronic inflammation