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Targeting Apoptosis Pathways in Cancer and Perspectives with Natural Compounds from Mother Nature

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Targeting Apoptosis Pathways in Cancer and Perspectives with Natural Compounds from Mother Nature Published OnlineFirst August 26, 2014; DOI: 10.1158/1940-6207.CAPR-14-0136 Cancer Prevention Review Research Targeting Apoptosis Pathways in Cancer and Perspectives with Natural Compounds from Mother Nature Faya M. Millimouno1,2,3, Jia Dong1, Liu Yang2, Jiang Li2, and Xiaomeng Li1 Abstract Although the incidences are increasing day after day, scientists and researchers taken individually or by research group are trying to fight against cancer by several ways and also by different approaches and techniques. Sesquiterpenes, flavonoids, alkaloids, diterpenoids, and polyphenolic represent a large and diverse group of naturally occurring compounds found in a variety of fruits, vegetables, and medicinal plants with various anticancer properties. In this review, our aim is to give our perspective on the current status of the natural compounds belonging to these groups and discuss their natural sources, their anticancer activity, their molecular targets, and their mechanism of actions with specific emphasis on apoptosis pathways, which may help the further design and conduct of preclinical and clinical trials. Unlike pharmaceutical drugs, the selected natural compounds induce apoptosis by targeting multiple cellular signaling pathways including transcription factors, growth factors, tumor cell survival factors, inflammatory cytokines, protein kinases, and angiogenesis that are frequently deregulated in cancers and suggest that their simultaneous targeting by these compounds could result in efficacious and selective killing of cancer cells. This review suggests that they provide a novel opportunity for treatment of cancer, but clinical trials are still required to further validate them in cancer chemotherapy. Cancer Prev Res; 7(11); 1081–107. Ó2014 AACR. Introduction such as, antiapoptotic proteins, growth factors, growth Cancer is a major public health problem and the second factor receptors, transcription factors, and tumor suppres- leading cause of mortality around the world, mainly Europe sors, which constituted the target for cancer treatment. and the United States with an incident rate of about 2.6 Prevailing treatment options have limited therapeutic suc- million cases per year (1, 2). It is characterized by unsched- cess in cancer in the past decade. The concept of chemo- uled and uncontrolled cellular proliferation in the spectrum prevention is gaining increasing attention because it is a of cell. Cancer incidence in developing countries has been cost-effective alternative for cancer treatment (5). Cancer prevailed by tumor types that are related to viral, genetic chemoprevention by natural compounds, especially phy- mutations, and bacterial contamination (3). Cancer has a tochemicals, minerals, and vitamins, in a number of studies in vitro in vivo high incidence and a long period of latency on its devel- under both and conditions has shown opment and in the progression of the sickness. There are promising results against various malignancies (6). numerous risk factors known concerning the development In the development of bioactive chemical, natural pro- of cancer including age, geographic area, and race (4). ducts have a rich and long history. Herbal medicines, as an However, cancer is mostly a preventable disease. important novel source with a wide range of pharmaceutical Regardless of whether a cancer specifically results from a potential, are being used to treat human ailments including genetic mutation and viral or bacterial contamination, the almost all kinds of cancer (7). recent extensive research indicated that most cancers are The involvement of multiple factors underlying develop- caused by dysfunction of many genes coding for proteins mental stages of cancer at epigenetic, genetic, cellular, and molecular levels is opening up enormous opportunities to interrupt and reverse the initiation and progression of the 1The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics disease and provide scientists and researchers with numer- and Cytology, Northeast Normal University, Changchun, China. 2Dental ous targets to arrest by physiologic and pharmacologic Hospital, Jilin University, Changchun, China. 3Higher Institute of Science and Veterinary Medicine of Dalaba, Dalaba, Guinea. mechanisms to delay the development of cancer. The aim of this review is to summarize recent researches on twelve F.M. Millimouno and J. Dong contributed equally to this work. (12) natural compounds, such as flavonoids (honokiol, Corresponding Authors: Xiaomeng Li, School of Life Sciences, Northeast magnolol, jaceosidin, and casticin), sesquiterpenes (parthe- Normal University, Renmin Street 5268, Changchun, China. Phone: 86- 431-85099285; Fax: 86-431-85099285; E-mail: [email protected]; nolide, costunolide, isoalantolactone, and alantolactone), and Jiang Li, Jilin University, Changchun 130021, China. Phone: 86- alkaloid (evodiamine), diterpenoids (oridonin and pseu- 186-86531019; Fax: 86-431-85579335; E-mail: [email protected] dolaric acid B), and polyphenolic (wedelolactone) focusing doi: 10.1158/1940-6207.CAPR-14-0136 on anticancer activity. The literature was screened from Ó2014 American Association for Cancer Research. various sites including PubMed, Scopus, and Elsevier www.aacrjournals.org 1081 Downloaded from cancerpreventionresearch.aacrjournals.org on September 28, 2021. © 2014 American Association for Cancer Research. Published OnlineFirst August 26, 2014; DOI: 10.1158/1940-6207.CAPR-14-0136 Millimouno et al. Science Direct Journal. Access to the Elsevier Science Direct effects, including antifungal, antihelmintic, antimicrobial, Journal was made possible through library of Northeast anti-inflammatory, antitrypanosomal, and antiproliferative Normal University, Changchun, China. We propose that effects on various cancer types as described in Tables 1 the development of natural compounds into new antican- and 2. cer agents has a bright future despite some difficulties. Role of Natural Compounds in Cancer Prevention Natural Sources and Biologic Activities of Plants provide an extensive reservoir of natural pro- Anticancer Chemopreventive Agents ducts, demonstrating important structural diversity, and Natural products are important and valuable resources offer a wide variety of novel and exciting chemical entities for drug development. Extensive researches have been car- and have a long history of use in the treatment of several ried out on the phytochemicals for their health-promoting illnesses. The significance of natural products in health potential. They have been found in fruits, vegetables, nuts, care is supported by a report that 80% of the global seeds, herbs, spices, stems, flowers, and tea. The phyto- population still relies on plant-derived medicines to constituent from these plants was extracted by several addresstheirhealthcareneeds(8).Itisalsoreported techniques, mainly high-performance liquid chromatogra- that 50% of all drugs in clinical use are natural products, phy, micellar electrokinetic chromatography, microemul- or their derivatives, or their analogs (9), and 74% of the sion electrokinetic chromatography, and their structures most important drugs consist of plant-derived active were elucidated on the basis of nuclear magnetic resonance ingredients (10). There are more than 3,000 plant species analysis (Fig. 1). that have been reported to be used in the treatment of The selected natural compounds among diterpenoids, cancer in modern medicine (11–14). sesquiterpenes, flavonoids, alkaloids, and polyphenolic There is a continued interest in the investigation of have been reported for their wide spectrum of biologic extracts of microorganisms, terrestrial plants, and marine Sesquiterpenes compounds Flavonoids compounds Diterpenoids compounds H3C OH CH OH 2 O OH O HO O OH H C CH OH O 3 3 OH PARTHINOLIDE HONOKIOL CH3 ORIDONIN Tanacetum parthenium Magnolia grandiflora Isodon rubescens H O HO O O H3C COOCH3 O O H H OH O COSTUNOLIDE MAGNOLOL PSEUDOLARIC ACID B Inula helenium Magnolia officinalis Pseudolarix kaempferi Polyphenolic compound CH H 3 OH OH O O HO O OH O OH O H H O CH CH 2 O 2 OH O O O ISOALANTOLACTONE JACEOSIDIN WEDELOLACTONE Inula helenium L. Artemisia princeps Wedelia chinensis Alkaloid compound OH CH3 H OCH3 O O O H3CO O H N H CO OCH3 H H 3 O N N CH CH2 OH 2 H ALANTOLACTONE CASTICIN Inula racemosa Vitex rotundifolia EVODIAMINE Evodia rutaecarpa Figure 1. Chemical structure of the promising natural compounds and major natural sources. 1082 Cancer Prev Res; 7(11) November 2014 Cancer Prevention Research Downloaded from cancerpreventionresearch.aacrjournals.org on September 28, 2021. © 2014 American Association for Cancer Research. www.aacrjournals.org Downloaded from Table 1. Natural source, pharmacologic action, and molecular targets of promising natural compounds Compound Natural source Mode of action Type of cancers Synergistic Major targets Flavonoids cancerpreventionresearch.aacrjournals.org Honokiol Magnolia officinalis, Magnolia Antioxidant, antiproliferation Glioblastoma, melanoma, Fluconazole, CDK1?, Bcl-2#, Bax", cyclin D1#, Published OnlineFirstAugust26,2014;DOI:10.1158/1940-6207.CAPR-14-0136 grandiflora, Magnolia spp. (cell-cycle arrest, apoptosis), gastric, leukemia, skin, Epigallocatechi n pAKT#, g-secretase activity#, anti-inflammation, colon, breast, ovarian, gallate (EGCG), TNFa g-secretase complex proteins#, antiangiogenesis, pancreatic, hepatocellular, PPAR-g?, COX-2?, NF-kB?, antiautophagy, colorectal, lung, prostate, EGFR/P13K/AKt#; JunB # and immunomodulation, human renal mesangial,
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