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137 Role of Natural Compounds in Preventing and Treating Breast [Frontiers in Bioscience, Scholar, 12, 137-160, March 1, 2020] Role of natural compounds in preventing and treating breast cancer Brianna Noel1, Santosh Kumar Singh1, James W. Lillard Jr. 1, Rajesh Singh1 1Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA, 30310 TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Natural Compounds 3.1. Quercetin 3.2. Tetrandrine 3.3. Curcumin 3.4. Silibinin 3.5. Thymoquinone 3.6. Resveratrol 3.7. Honokiol 3.8. Diosgenin 3.9. Genistein 3.10. Garcinol 4. Combination Effect 5. Conclusions 6. Acknowledgments 7. References 1. ABSTRACT Breast cancer (BrCa) is the most commonly development of BrCa, suppress the growth of cancer diagnosed cancer and the second leading cause of cells, and promote cell death. We conclude that cancer-related death in women. Alarming increases natural compounds are efficient, effective and in the cases quests for more effective treatment of promising agents for treating BrCa other than BrCa. As most chemotherapeutic drugs are therapeutic methods. associated with drug resistance, cancer relapse, and side effects, scientists are turning to agents with more 2. INTRODUCTION efficacy, such as natural compounds for treatment and prevention of BrCa. Selected natural Breast cancer (BrCa) is the most frequent compounds, substances derived from living type of cancer diagnosed in women worldwide (1). organisms, promote apoptosis and inhibit metastasis, Approximately 1 in 8 women are diagnosed with BrCa preventing cancer growth. As a result, these sometime in their lives (2). In the United States, compounds have the potential to suppress BrCa roughly 266,120 women are estimated to have been progression, thus increasing patient survival rates diagnosed with invasive BrCa in 2018 (3). In addition, and decreasing the number of BrCa-related deaths. it is the second most common cause of cancer- In this review, we summarize natural compounds that related death in females globally (4). Therefore, have displayed, anti-cancer effects on BrCa cells in effective treatments for BrCa are needed to reduce various studies. These natural compounds inhibit the the numbers of deaths from BrCa. Moreover, BrCa is 137 Natural compounds in breast cancer therapy more frequently diagnosed in certain races or plants, including Allagopappus viscosissimus, ethnicities. African American women younger than Opuntia ficus-indica var. saboten, Lychnophora age 40 are two times more likely to develop BrCa in staavioides, and Rhamnus species (12, 13). The comparison to white women of the same age. geographical distribution determines, it is found in Another BrCa disparity is that African, American and more than twenty pants material (14). This compound Hispanic females are more at risk to be diagnosed present in various vegetables and fruits and in wine, with aggressive and advanced forms of BrCa (5). tea, and coffee (15), has anticancer, antioxidant, These BrCa disparities point to a need for more antitumor, and anti-inflammatory properties (16). QC efficient treatments for BrCa. promotes apoptosis in a wide variety of cells, including those of prostate, lung, breast, colon, and Due to the high incidence of BrCa, effective cervical cancers (15). In addition, nanoparticles agents are needed to treat this cancer (6). Surgery, containing QC reduce the growth of cancer cells and chemotherapy, radiotherapy, and hormone therapy cause them to undergo apoptosis, (12). To promote are the most frequently used methods of treatment apoptosis of cancer cells, QC decreases the for BrCa. Although BrCa is typically treated with expression of anti-apoptotic proteins, such as chemotherapeutic drugs, the development of drug survivin, Bcl-xL, and Bcl-2, and increases the resistance, the occurrence of side effects, and expression of the pro-apoptotic proteins, such as Bad reoccurrence of the disease indicate that these drugs and Bax, (15). Since it targets cancer cells and have limited efficacy (4, 7). The well-studied drug causes them to undergo apoptosis, this compound is efflux genes are MDR1, ABCG2, and BCRP (7). The a potential therapeutic for treating various cancers side effects are unpredictable and depend upon the (17). chemotherapeutics; some common effects include nausea and vomiting, neuropathy, constipation, QC is a promising agent for prevention and diarrhea, and trouble breathing. Since clinicians need therapy of BrCa (12). For BrCa cells (BT-20 and therapies that treat BrCa without extensive side MCF-7), QC promotes apoptosis by inducing the effects and drug efflux, there is a need for replacing inactivation of c-FLIPL and upregulating DR5. In present chemotherapy drugs with natural addition, QC arrests proliferation of BrCa cells (MCF- compounds, which are organic chemical substances 7) by inhibiting the cell cycle (15). Moreover, it inhibits that are the products of living organisms (8) (Figure the growth and invasive capacity of BrCa stem cells 1). Natural compounds are considered to be effective (MDA-MB-231) and downregulates various proteins, in the treatment of BrCa, as they affect several including aldehyde dehydrogenase 1A1, epithelial targets and have minimal or no side effects (Table 1). cell adhesion proteins, and others that are associated In addition, several studies have been identified in with the growth of BrCa cells. Therefore, by natural compound targeted therapies on subtypes of downregulating these proteins, the proliferation of breast cancers (Basal-like, Luminal and HER-2) (9). BrCa cells is inhibited, showing that QC has In certain cases, natural compounds are safer, faster, anticancer properties (17). Thus, since QC promotes cheaper, and less toxic in treatment of BrCa (10). apoptosis of BrCa cells, it is likely to be effective in Some of these compounds induce apoptosis and treating BrCa. function in chemo-sensitization (11). The aim of this review is to evaluate natural compounds and show 3.2.Tetrandrine how they can be more effective than other therapeutic methods in treating BrCa. Tetrandrine, which demonstrates anti- proliferation and antitumor properties (18), is a 3. NATURAL COMPOUNDS dibenzyl tetrahydro isoquinoline alkaloid present in Stephania tetrandra, an Asian herb (Chinese plant) 3.1. Quercetin used for medicinal purposes (18, 19). This natural compound has proapoptotic effects on cancers, Quercetin (QC), a flavonol from the including leukemias, melanomas, and prostate and flavonoid group of polyphenols, is produced by breast cancers (18). Tetrandrine has 138 © 1996-2020 Natural compounds in breast cancer therapy Figure 1. Chemical structure of natural compound leads as therapeutics in treating breast cancer. pharmacological properties in that it contributes to numerous BrCa cell lines, and it promotes cell death the blockade of positive ion channels and blocks in cells that are resistant to apoptosis. Due to various drug resistance proteins (19). Used to treat autophagy, apoptosis-resistant cell lines that have various cancers, tetrandrine affects the resistance of low expression of caspase 3, caspase 7, and Bax, tumor cells (20), and it reverses drug resistance in Bak undergo cell death when treated with tetrandrine. human BrCa cells (21). Further, tetrandrine induces Thus, tetrandrine is useful in activating cell death autophagy. As a result, cells that are resistant to amongst cancer cells (22), and it shows properties apoptosis and thus are resistant to cell death in that make it a promising treatment for the prevention general, undergo autophagic cell death (22). and treatment of BrCa (21). Therefore, since tetrandrine decreases the growth of cancer cells, it is a promising agent for treating 3.3. Curcumin various cancers. Curcumin (CUR),a component of the spice Tetrandrine displays a preventive effect plant Curcuma longa turmeric, probably originated against the growth of inflammatory and breast tumor- from South and South-East Asia, is commonly used initiating cells by killing these cells. This compound for medicinal purposes and is effective in the reduces mammosphere formation, which is a treatment of a variety of cancers (23-25). It has anti- surrogate for the proliferation of cancer cells, and it inflammatory, anti-tumor, anti-microbial, anti- reduces the protein expression of aldehyde oxidative, and anticancer properties, and it has anti- dehydrogenase. For SUM-149 and SUM-159 BrCa carcinogenic effects on squamous cell carcinomas cells, tetrandrine exhibits anti-proliferative properties. and on lung, breast, pancreatic, brain, head and In addition, by downregulating aldehyde neck, and colorectal cancers (24-27). In addition, dehydrogenase proteins, it demonstrates anti- CUR displays anti-proliferative effects on cancer proliferation characteristics because these proteins cells, including those of melanoma and mantle cell are related to the growth of BrCa cells (19). For BrCa lymphoma and hepatic, ovarian, and prostatic MCF-7/TAM cells, tetrandrine reverses drug carcinomas (28, 29). CUR regulates the expressions resistance of tamoxifen. As an activator of of several proteins, including inflammatory cytokines autophagy, tetrandrine has pro-autophagic effects on and enzymes, transcription factors, and gene 139 © 1996-2020 Natural compounds in breast cancer therapy Table 1. Understanding the effectiveness of natural compounds in BrCa therapy Natural Source Action Reference Compound Curcumin Curcuma longa Promotes apoptosis; blocks angiogenesis and tumor metastasis; regulates the NF-κB (25, 26) signaling pathway; downregulates
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