Anticancer activity and therapeutic uses of catechins on breast, prostate and lung cancer: Future perspective and clinical proofs by Md. Rokibul Hasan Bhuiyan in Journal of Clinical Case Reports Medical Images and Health Sciences

 Anticancer activity and therapeutic uses of catechins on breast, prostate and lung cancer: Future perspective and clinical proofs by Md. Rokibul Hasan Bhuiyan in Journal of Clinical Case Reports Medical Images and Health Sciences

Abstract

Breast, Lung and Prostate cancer are Leading Environmental issue among of them Breast cancer is the most prevalent cancer in the world and the second leading cause of cancer related mortality among women. These all cancer treatment options include surgery, chemotherapy, hormone therapy and radiation. However adverse effect from chemotherapy, hormone therapy and radiation are frequently reported and multidrug resistance, recurrence and the absence of treatment for metastasis are the main issue with breast, lung and prostate cancer treatment. Due to safe nature, dietary phytochemicals have recently become effective tools for the treatment and prevention of cancer. Catechins which are included in many commonly consumed fruits and vegetables, have been demonstrated to reduce breast, lung and prostate cancer cell growth and triggered apoptosis. In this review the anticancer characters and therapeutic uses of catechins are presented for breast, prostate and lung cancer cell line.

Keywords: Breast cancer, catechins, In vitro, In vivo, lung cancer, prostate cancer.

Abbreviations: AKT, protein kinase B; Apaf-1, apoptotic protease activating factor 1; AIF, apoptosis inducing factor; Bcl-2, B-cell lymphoma 2; Bax, Bcl-2 associated X; Bad, Bcl-2 associated agonist of cell death; CDK4, cyclin-dependent kinase 4; CDC2, cell division cycle2; COX-2, cyclooxygenase-2; CYP19/1A1/1A2, DNMT1/3a, DNA (cytosine-5)-methyltransferase 1/3a; DMBA, 9,10-dimethyl-1,2-benzanthracene; ER-α, estrogen receptor- α; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; FoxM1, forkhead box M1; GSTA1, glutathione S-transferase A1; HDAC, histone deacetylases; HER2, human epidermal growth factor receptor 2, microtubule-associated protein light chain 3; mTOR, mammalian target of rapamycin; MMP-2/9, matrix metalloproteinase-2; MAPK, mitogen-activated protein kinases; NQO1, NAD(P)H quinone dehydrogenase 1; PTEN, phosphatase and tensin homolog; RARbeta2, retinoic acid receptor beta2; STAT3, signal transducer and activator of transcription 3; TrxR1, thioredoxin reductase 1; VEGFR-2, vascular endothelial growth factor-2.

INTRODUCTION

An abnormal development of breast tissue known as cancer is a problem for world health. It accounts for 25% of all cancer cases and 15% of all cancer deaths worldwide, making it the most prevalent cancer and the main cancer related killer of females. [1] There are presently several treatment options for breast cancer, including surgery, chemotherapy, hormone therapy and radiation. Unfortunately, this current therapy does not always effectively battle the disease, and they have had only a minimally significant influence on the cancers notable morbidity. In addition, treatments like radiation. Hormone therapy, and chemotherapy frequently have negative effects, and tumor recurrence can occasionally occur after a tumor has been surgically removed. Another issue in the management of cancer is drug resistance to many medications. Due to their lack of side effects, low cost and low toxicity when compared to manufactured medications, dietary phytochemicals have recently gained recognition as helpful agents for the prevention and treatment of cancer. Over the past ten years, a number of phytochemicals have been discovered in plants and human diets. Research has revealed that these phytochemicals are crucial in the prevention of several malignancies, including breast cancer. Numerous phytochemicals have demonstrated potential to prevent breast cancer by modifying cell growth, apoptosis, oxidative stress, inflammation, angiogenesis and a variety of cell signaling pathways. [2] The effectiveness of several dietary phytochemicals in breast cancer treatment and prevention was evaluated in several clinical studies [3]. Dietary phytochemicals known as catechins have received extensive research and attention due to their wide range of biological functions and molecular targets. Several well-known fruits and vegetables contain the phenolic component catechins (Table-1). Among the phenolic acids, catechins have been studied the subject of in depth research in lung, prostate and breast cancer. (Fig 1)

Breast cancer, prostate cancer and lung cancer have all been reported to be treated and prevented by catechins. Their effectiveness has been proven in cancer cell lines and animal models (Table-2). The use of these medicines for prevention and therapy of breast cancer had not been widely covered previously, despite numerous great studies providing information on the anticancer potential of these compounds against other malignancies. [4], [5] Breast cancer is very common now a days and patient number is increasing every day. Lung cancer is common in poor countries with air pollution in the cities and happening for many other reasons as well. Prostate cancer is number one enemy for male and elderly people are affected by this cancer mostly. All cancer is dangerous and abnormal cell growth known as cell proliferation is very rapid in this cases. [6] Scientists are hopeful about natural phytochemicals and in many research it is proven that, phytochemicals can decrease cancer growth and most of the cases they are used as prevention from cancer and other dangerous diseases. Lung cancer is common and it infects the lungs then it can spread other part of the body. Diagnosis of prostate cancer is very important because in the developing world most people are not aware about it. Therefore, the potential use of these phytochemicals in the treatment and prevention of breast cancer, prostate cancer and lung cancer is critically examined in this study.

Study of catechins effect upon Breast cancer cell line

Breast cancer is a diverse illness that affects more women than any other type of cancer worldwide. Chinese epidemiological research have demonstrated that tea drinking has positive benefits on breast cancer prevention and recurrence decrease, particularly for women who drink more than 4 cups of tea each day [12] Numerous researches have examined the mechanism through which tea catechins inhibit breast cancer. Tea catechins, such as EGCG, ECG, and EC have a potent antiangiogenic impact that has been demonstrated by antiproliferative and pro-apoptotic effects in breast cancer cells for the reduction of carcinogen induced ROS stress [13] The subsequent reports of the inhibitory effects of EGCG on breast cancer cell migration and proliferation were linked to down-regulated of the PI3K/Akt and p53/Bcl-2 signaling pathways as well as modification of telomerase. [14] Previous studies have also demonstrated that tea catechins have an impact on receptor mediated pathways linked to proliferation and apoptosis, inhibiting the invasive behavior of breast cancer cells by lowering levels of angiogenesis factors like VEGF and epidermal growth factor receptor (EGFR), and blocking the expression of signal transducer and activator of transcription-3(STAT-3) and nuclear factor by (NF-B). Additionally, estrogen receptor(ER) binding target proteins with relatively high affinities, focal adhesion kinase(FAK) signaling pathway inhibition, and their antiproliferative action via blocking ER-specific inhibitor were also identified. [15] Both the methylation status and gene expression have been linked to EGCG. The epigenetic impact of EGCG in downregulating DNA methyltransferases (DNMTs) and reducing the expression of the SCUBE2 gene in breast cancer cells was identified. Deb and colleagues also discovered that 20M EGCG reduced the expression of the epigenetically suppressed TIMP-3 gene. [16] Additionally, ER+PR+cancer cells were used to evaluate the anticancer effects of EGCG by epigenetic downregulation of ER via activation of p38/MAPK/CK2 [17] . In animal models, treatment of EGCG has been demonstrated to inhibit the development of tumors caused by breast cancer cells. The observations in a xenograft model instance revealed that EGCG inhibited tumor associated macrophage infiltration and M2 polarization, which in turn lowered tumor development following intraperitoneal administration of 10mg/kg EGCG on days 7,9 and 11. [18] GTCs are crucial for the prevention and treatment of human breast cancer because they have the capacity to decrease breast carcinogenesis through several targets. MCF-7 cells with 50 μM (-)-Epigallocatechin-3-gallate (EGCG) induce apoptotic changes, including mitochondrial membrane potential changes and activation of c-JUN N-terminal kinase (JNK), caspase-9, -3 increase oxidative stress, upregulation of Bax protein levels and down regulation of Bcl2 protein, shifting the Bax-Bcl 2 ratio to favor apoptosis. [19] (HSUUW, Y.-D et al 2007)  MCF-7 having a high level of ERα Expression treated with various EGCG concentrations ERα and ps2 mRNA expressed cytotoxicity and drug sensitivity. [20] Estrogen receptor positive (ERα+) and (ERα-) breast cancer cell, eg MCF-7, T47D, MDA-MB-231 and HS578T cells incubate EGCG, EGC or ECG individually and combination for 7 days.  ERα- human breast cancer cell were more susceptible above of all three catechins. Low concentration of catechins are cytotoxic to human breast cancer cells. [21] The structural, physical and chemical properties of the CatNps including PLGA-Cat interactions and surface characterization analyzed by dynamic light scattering (DLS), Fourier transform infrared (FT-IR) and Scanning Electron Microscopy (SEM). MCF-7 Cells were treated with CatNps for 48h led to decrease in cell viability with IC50 value 22.59 μg/ml. low encapsulation efficiency of CatNps expressed antioxidant efficacy. [22] In this review proved that catechins have played biggest role in treating breast cancer.

Overview of catechins effect upon Prostate cancer cell line

The most prevalent illness in men and a significant public health issue is prostate cancer. In a proof of concept study that lasted a year, green tea catechins were given orally. This treatment significantly showed the development of prostate cancer from high grade intraepithelial neoplasia, and it also reduced the levels of the serum markers IGF-1, VEGF and prostate specific antigen in patients with prostate cancer [23] More recently, green tea has been utilized as a sensitizer to enhance prostate cancer radiation results. Numerous studies have suggested that GTCs prevented prostate cancer at various stages of development by inhibiting the production of the prostate specific antigen(PSA), androgen receptor(AR), transcriptional activity, activating chromatin proteins, and methylation silenced genes [24] Additionally, by upregulating the expression of p21 [25] showed that 20,40, and 80M of EGCG had noteworthy impacts on G0 /G1 phase cell cycle arrest and death when exposed prostate cancer cells to tea catechins. Further investigation led the team to the discovery of the related molecular pathway for EGCG (5, 10, 20, and 40M) induced cell cycle dysregulation and apoptosis which was cdk inhibitor [26]. Additionally, it has been shown that EGCG (5M) inhibits cell motility and invasion via altering lipid rafts in a way that prevents the activation of the c-Met receptor [27] . According to other research, EGCG can cause prostate cell death by upregulating the expression of ID2. [28] In transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, the inhibitory effects of EGCG against prostate cancer development and metastases were reported. After administering 0.06% EGCG in drinking water for 28 weeks, the results revealed that EGCG treatment can reduce cell proliferation and induce apoptosis by down regulating IGF1, IGF-1R, p-ERK1/2, COX-2 and iNOS level. [29] Furthermore, according to 0.06% EGCG added to mice,s drinking water can prevent prostate cancer by reducing a molecular chaperone that supports the cancerous phenotype. Eased on the aforementioned research, EGCG would be a fantastic chemoprevention agent for prostate cancer. [30] The effect of lysine, proline, arginine, asvorbic acid and green tea extract induce PC3 cell in vivo and vitro. The expression of MMPs, VEGF, Ki67 and fibronectin. Group A was fed a regular diet and Group B was fed 0.5% nutrient mixture for 4 Weeks and inhibition of tumor growth measured. [31] Growth suppression and apoptosis appear on HH870, DU145, HH450, HH639 and 50% cell proliferation and suppressed on DU145, HH870, HH450, HH639 on 24, 27, 29, 30 µM whereas EGCG inhibit cell growth DU145, HH870, HH450, HH639 at concentrations 89, 45, 62 and 42 µM. [32] Cell proliferation and migration of KFs suppressed by EGCG and IC50 54.4 µM. EGCG inhibited PI3K and extracellular signal regulated ERK1/2 and STAT3 Strongly suppressed proliferation, migration and collagen production by KFs.[33] Daily treatment of three GTCs capsule 200 mg each and total 600 mg/d after 1 year tumor diagnosed among the 30 GTCs treated men. On the other hand nine cancers were found among men and secondery observation administration on GTCs also reduced lower urinary tract symptoms. [34] The above information proof that catechins plays biggest role on prostate cancer according to research result.

Investigation of catechins activity upon Lung cancer cell line.

A significant portion of cancer related deaths are caused by lung cancer, which accounts for 80-85% of cases. Previous research has suggested that the injection of GTCs can prevent the onset of lung carcinogenesis in all variety of chemically induced and transgenic animal models. By inhibiting important protein kinases, green tea’s catechins have been demonstrated to have anti-cancer properties. Modulation of signaling molecules and gene expression, including those of cycclin D1, VEGF, Bax, Bcl-2, p21, p53, COX-2, Caspase-3, 7 and 9, has also been seen. [35] Additionally, research by Lu and colleagues using 4-Methylnitrosamino-1-3-pyridyl-1-butanone(NNK) induced A/J mice showed that GTCs were more effective than caffeine at inhibiting lung tumorigenesis. The treatment consisted of 0.5% Polyphenon E (65% EGCG) or 0.044% caffeine aas the only source of drinking fluid for 52 weeks. It was also claimed that EGCG can significantly inhibit the phosphor. [36] Treatment of H1299 and Lu99 NSCLC cells with 50 and 100M EGCG confirmed the inhibition of lung metastasis of melanoma cells by admission of EGCG. The related mechanisms were linked to the downregulation of epithelial mesenchymal transition (EMT), tyrosine phosphorylation of matrix metalloproteinases-9 (MMP-9) and FAK activities. [37] H1299 cells growth was found to be decreased by the use of 0-20M EGCG. This was followed by an increase in tumor cell death, high affinity EGCG binding to the Ras-GTPase activating protein SH3 domain binding protein 1 (G3BP2), and the production of ROS. [38] Additionally, nicotine induced migration, invasion, and angiogenesis in NSCLC cells wirh 10-100M EGCG have been demonstrated to be inhibited. As a result, EGCG had a substantial impact in inhibiting tumorigenesis and metastasis in lung cancer cells. [39] Similar to this, it was shown that EGCG (0-120 µM) treatment of human small-cell lung cancers cells resulted in the deregulation of telomerase activity as well as Caspase-3, and 9 activities. [40] Induction of apoptosis and cell growth suppression by EGCg in a number of cell culture studies. Cell proliferation and induction modulated apoptotic cell death evaluated in A549 cell line 100 µM for 24 h. The mRNA expression level of B lymphocyte decreased at that dose. [41] EGCg suppresses oncogenic pathways and induces cell cycle arrest r apoptosis by caspase 3/7. Catechin mixture cans upregulate p53 receptor a potent apoptosis inducer that functions p53 dependent pathways in A549 cells. [42] Inhibitory effect of tea polyphenol on the growth of human lung cancer cell line and PC9 cells. The mechanism of growth inhibition by EGCG studied to cell cycle regulation that 50 -100 μM increase cell cycle arrest at G2-M phase. [43] 14 Protein identified that changed expression 2 fold after GTE treatment. These protein involved calcium binding, cytoskeleton and motility, metabolism, detoxification or gene regulation. Upregulation of several genes that modulate actin remodeling and cell migration, including lamin A/C. GTE alters the levels of many protein involve growth, motility and apoptosis. [44] As a result, catechins can function as new agents to stop or slow the development of lung tumors.

Future perspective and clinical proofs

In Bio Medical and Medicine world, Dietary phytochemical keeps biggest role for life and prevent disease. The demonstrated evidence suggests that Catechins could be used as a potential agent to develop a comprehensive competent strategy towards the treatment and prevention of Breast, Lung and Prostate cancer cell line. Catechins have been reported to exert anti Breast, Lung and Prostate cancer effects via induction of apoptosis, cell cycle arrest and inhibition of tumor cell proliferation (Fig 1). Based on the research original investigations, almost all studies have been performed following in vitro models. To confirm their efficacy, in vivo studies using proper animal models of both cancers need to be done. Catechins have been studied in most of the studies. As agent for sensitization and potentiation of chemotherapeutic drugs, more studies need to be done. Preclinical studies on catechins as an anticancer agent for colon cancer control need attention about bioavailability improvement (Table 1) As well as, combinational therapy may also be advantageous for bioavailability improvement. Identification of novel target proteins and pathways in which they function, epidemiological studies, clinical trials and determination of safety profile are also needed. At a glance, In vitro and In vivo data examined in this review suggest that catechins are promising agents in the prevention and intervention of Breast, Lung and Prostate cancer.

Acknowledgements

This Research article was originally written by Md. Rokibul Islam Bhuiyan. This paper was reviewed and Data collected by Md. Sadikuj Jaman.

Compliances with Ethical Standards:

Funding Information

No Fund receipt from any institution or Company.

Contributions

The first draft of the manuscript was originally written by Md Sadikuj Jaman and Md Rokibul Hasan Bhuiyan . All authors contributed to the study conception and design. Table arrangement, Data collection and analysis, Figure design, Material preparation was done by Md. Sadikuj Jaman, Md. Rokibul Hasan Bhuiyan. Both authors read and approved the final manuscript.

Conflict of Interest

The authors have no relevant financial or non-financial interests to disclose.

Ethics declarations

Ethical approval and consent to participate

This study discuss with animal model and clinical application. Informed consent was obtained from all individual participants included in the study.

Patient consent for publication

Not Applicable

Competing interests

The authors declare that this manuscript will save humanity from cancer and tumor related disease.

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