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Mechanistic Evaluation of Phytochemicals in Breast Cancer Remedy: Current Understanding and Future Cite This: RSC Adv.,2018,8,29714 Perspectives

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Mechanistic Evaluation of Phytochemicals in Breast Cancer Remedy: Current Understanding and Future Cite This: RSC Adv.,2018,8,29714 Perspectives RSC Advances View Article Online REVIEW View Journal | View Issue Mechanistic evaluation of phytochemicals in breast cancer remedy: current understanding and future Cite this: RSC Adv.,2018,8,29714 perspectives Muhammad Younas,a Christophe Hano,b Nathalie Giglioli-Guivarc'hc and Bilal Haider Abbasi *abc Breast cancer is one of the most commonly diagnosed cancers around the globe and accounts for a large proportion of fatalities in women. Despite the advancement in therapeutic and diagnostic procedures, breast cancer still represents a major challenge. Current anti-breast cancer approaches include surgical removal, radiotherapy, hormonal therapy and the use of various chemotherapeutic drugs. However, drug resistance, associated serious adverse effects, metastasis and recurrence complications still need to be resolved which demand safe and alternative strategies. In this scenario, phytochemicals have recently gained huge attention due to their safety profile and cost-effectiveness. These phytochemicals modulate various genes, gene Creative Commons Attribution-NonCommercial 3.0 Unported Licence. products and signalling pathways, thereby inhibiting breast cancer cell proliferation, invasion, angiogenesis and metastasis and inducing apoptosis. Moreover, they also target breast cancer stem cells and overcome drug resistance problems in breast carcinomas. Phytochemicals as adjuvants with chemotherapeutic drugs have greatly enhanced their therapeutic efficacy. This review focuses on the recently recognized molecular Received 7th June 2018 mechanisms underlying breast cancer chemoprevention with the use of phytochemicals such as curcumin, Accepted 15th August 2018 resveratrol, silibinin, genistein, epigallocatechin gallate, secoisolariciresinol, thymoquinone, kaempferol, DOI: 10.1039/c8ra04879g quercetin, parthenolide, sulforaphane, ginsenosides, naringenin, isoliquiritigenin, luteolin, benzyl rsc.li/rsc-advances isothiocyanate, a-mangostin, 3,30-diindolylmethane, pterostilbene, vinca alkaloids and apigenin. This article is licensed under a 1 Introduction therapy.3–8 Current therapeutic interventions in breast cancer remedy include radiation, surgical exclusion and the use of Breast cancer is one of the most commonly diagnosed cancers various chemotherapeutic drugs such as paclitaxel, doxorubicin, Open Access Article. Published on 22 August 2018. Downloaded 9/24/2021 3:20:28 PM. around the world and accounts for a large proportion of cisplatin, docetaxel, carboplatin, epirubicin, bevacizumab and mortalities in females. The American Cancer Society estimated cyclophosphamide.9,10 However, the incidences of drug resistance that in 2017, there will be an expected 63 410 new cases of in situ, and serious side-effects associated with these treatment methods 252 710 cases of invasive and 40 610 cases of breast cancer have greatly reduced their therapeutic potential.11 These mortalities across women in the United States alone.1,2 On the complications propel researchers to look into alternative and basis of expression of the estrogen receptor (ER), breast cancer is safer chemotherapeutic strategies. categorized into ER-positive and ER-negative types. The human Human beings have always been suffered from infections by epidermal growth factor receptor 2 (HER2) and progesterone fungi, parasites, bacteria, viruses and many health disorders receptor (PR) further divide breast cancer into several molecular such as pain, inammation, digestive complications and colds subtypes like HER2-positive, luminal A and luminal B. These etc.12 Recent medicines, based on antibiotics and synthetic types of breast carcinomas respond to aromatase inhibitors or drugs, have come into practice during the previous 150 years. hormonal therapy. However, another type of breast cancer, Before that, humans had to depend on drugs derived from known as basal-like or triple negative breast cancer (TNBC), lacks plants, animals and fungi. The curing of health disorders and these three receptors and thus does not respond to hormonal infections with herbal medicines includes active natural prod- ucts, known as secondary metabolites or phytochemicals, which are found in almost all plant species.12 Secondary metabolites aDepartment of Biotechnology, Quaid-i-Azam University, Islamabad-45320, Pakistan. encompass a diverse group of organic compounds which have E-mail: [email protected]; Fax: +92-51-90644121; Tel: +92-51-90644121; +33- a vital role in plant defence systems and assist the interaction 767-97-0619 with the biotic environment. Many secondary metabolites like bLaboratoire de Biologie des Ligneux et des Grandes Cultures (LBLGC), Plant Lignans phenolics, alkaloids and terpenes are classied on the basis of ´ ´ Team, UPRES EA 1207, Universite d'Orleans, F 28000 Chartres, France ff cEA2106 Biomolecules et Biotechnologies Vegetales, Universite Francois-Rabelais de their biosynthetic origin which possess di erent biological Tours, Tours, France properties and are employed as pharmaceuticals, avors, 29714 | RSC Adv.,2018,8,29714–29744 This journal is © The Royal Society of Chemistry 2018 View Article Online Review RSC Advances colors, agrochemicals, fragrances, food additives and bio- behaviours in breast cancer cells (Fig. 3 & 4). Moreover, these pesticides.13–15 Secondary metabolites specically modulate compounds greatly enhanced the therapeutic efficacy of a molecular target in humans or animals. Such targets oen different anti-cancer drugs, overcame drugs resistance in include neuroreceptors, ion pumps, ion channels and elements breast cancer cells and also achieved sensitization to radia- of the cytoskeleton or enzymes degrading neurotransmit- tions.53–58 The compounds targeted breast cancer stem cells ters.12,16–20 An estimated more than 5000 distinct phytochemi- (bCSCs)/progenitor cells.59,60 CSCs are mainly involved in cals have been recognized in vegetables, fruits and grains, promotion of invasion, metastasis, abnormal proliferation, however, a large proportion is yet to be identied and under- recurrence and drug resistance.61 The self-renewal capability stood before we can completely comprehend their health of CSCs is related to the regulatory pathways of Notch, Wnt/b- benets in whole foods.21 Phytochemicals can be categorized catenin, hedgehog and P13K/Akt. These pathways might also À into different classes such as phenolics, terpenes, organosulfur contribute in the maintenance of CD44+/CD24 /low bCSCs compounds and alkaloids (Fig. 1).393,394 The molecular struc- stemness.59,62 Dandawate et al. (2016) reviewed the role of tures of various phytochemicals involved in breast cancer che- phytochemicals in targeting bCSCs.60 Abdal Dayem et al. moprevention with their major plant sources are given in (2016) reviewed the effect of polyphenols against breast Table 1. cancer and CSCs (Fig. 5).395 Petric et al. (2015) reviewed some Phytochemicals display diverse range of disease- phytochemicals modulating signalling pathways in breast preventing or protective effects. They have been used since and hormone related cancers.63 Moreover, Siddiqui et al. ancient times to cope with various ailments including cancer, (2015) have also put some light on therapeutic effect of diabetes, cardiovascular diseases, inammation, neurolog- phytochemicals in breast cancer.64 In this review article, we ical disorders and skin diseases etc.22–28 Numerous epidemi- summarize various phytochemicals that are involved in ological studies have predicted reduced cancer incidence breast cancer prevention, by putting in view the recently with the use of phytochemicals.29–31 Phytochemicals such as recognized molecular mechanisms, which may serve useful 32 33,34 Creative Commons Attribution-NonCommercial 3.0 Unported Licence. curcumin, resveratrol, epigallocatechin gallate in future drugs development. (EGCG),35,36 silibinin,37 benzyl isothiocyanate,38,39 genistein,40 kaempferol,41,42 thymoquinone,43 quercetin,44 parthenolide,45 sulforaphane,46 naringenin,47,327,330 isoliquiritigenin48,49 and ginsenosides50–52 have been shown to suppress breast carci- 2 Literature search noma via modulation of various signalling transduction This review was conducted using various search engines pathways, genes and gene products. These phytochemicals including Google Scholar, PubMed, and Scopus by putting exert anti-breast cancer effects by inducing cellular apoptosis keywords such as breast cancer, chemoprevention, phyto- and reducing cell proliferation through modulation of This article is licensed under a chemicals and individual names of respective phytochemicals various targets (Fig. 2 & 4). Additionally, phytochemicals plus breast cancer. All the research articles included in here are inhibit the angiogenesis, metastasis and migratory from the last half decade: 2012–2018. Open Access Article. Published on 22 August 2018. Downloaded 9/24/2021 3:20:28 PM. Fig. 1 Classification of phytochemicals involved in breast cancer chemoprevention. This journal is © The Royal Society of Chemistry 2018 RSC Adv.,2018,8,29714–29744 | 29715 View Article Online RSC Advances Review Creative Commons Attribution-NonCommercial 3.0 Unported Licence. This article is licensed under a Open Access Article. Published on 22 August 2018. Downloaded 9/24/2021 3:20:28 PM. Representative molecular structures of phytochemicals with their major plant sources Table 1 29716 | RSC Adv.,2018,8,29714–29744 This journal is © The Royal Society of Chemistry 2018 View Article Online Review RSC Advances Creative Commons Attribution-NonCommercial 3.0 Unported Licence. This article
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