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Anticancer Potential of Aloes: Antioxidant, Antiproliferative, and Immunostimulatory Attributes

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Anticancer Potential of Aloes: Antioxidant, Antiproliferative, and Immunostimulatory Attributes Reviews 843 Anticancer Potential of Aloes: Antioxidant, Antiproliferative, and Immunostimulatory Attributes Authors Eli Harlev1, Eviatar Nevo1, Ephraim P. Lansky1, Rivka Ofir 2, Anupam Bishayee3 Affiliations 1 Institute of Evolution and International Graduate Center of Evolution, University of Haifa, Mount Carmel, Haifa, Israel 2 Dead Sea and Arava Science Center and Ben Gurion University of the Negev, Beere Sheva, Israel 3 Department of Pharmaceutical and Administrative Sciences, School of Pharmacy, American University of Health Sciences, Signal Hill, CA, USA Key words Abstract nosy. Structures of key compounds are provided, l" Aloe vera ! and their pharmacological activities reviewed. l" Xanthorrhoeaceae Aloe is a genus of medicinal plants with a notable Particular attention is given to their free radical l" immunobiology history of medical use. Basic research over the scavenging, antiproliferative, and immunostimu- l" antiproliferative past couple of decades has begun to reveal the ex- latory properties. This review highlights major re- l" anticancer ʼ l" aloe‑emodin tent of Aloe s pharmaceutical potential, particu- search directions on aloes, reflecting the enor- l" acemannan larly against neoplastic disease. This review looks mous potential of natural sources, and of the ge- at Aloe, both the genus and the folk medicine, nus Aloe in particular, in preventing and treating often being called informally “aloes”, and delin- cancer. eates their chemistry and anticancer pharmacog- Introduction (l" Fig. 2), included in the gel of the Aloe vera leaf, ! while the immunostimulating activity is mainly Aloe is a genus of small to large, evergreen peren- due to acemannan (l" Fig. 2), a mucopolysaccha- nials, with fleshy, sword to lance-shaped leaves ride of Aloe vera gel, and to aloemannan included belonging to the Xanthorrhoeaceae family. This in the leaves of Aloe arborescens – both plants dis- genus comprises about 400 species native to sub- playing antitumor activities in vitro through acti- Saharan Africa, the Saudi Arabian Peninsula, and vation of immune responses [4]. Polyphenols and many islands of the Western Indian Ocean. other reactive oxygen species (ROS) scavengers Although thought to grow only in hot and dry act preventively through their antioxidant effects. climates, Aloe plants (l" Fig. 1) actually grow in a Aloe vera Burm. f. (also called Aloe barbadensis variety of climates, including desert, grassland, Miller) (l" Fig. 1) is the most known species of received February 1, 2012 coastal, or even alpine locations [1,2]. However, the Aloe genus and the most researched one. Over revised March 11, 2012 the majority are arid zone plants inhabiting the 4000 studies were performed on the effectiveness accepted March 26, 2012 deserts of South Africa. These succulents, sub- of Aloe vera in medical treatment, part of which This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Bibliography jected to the dry areas of the tropics and sub- addressed their role in recovery from diagnosed DOI http://dx.doi.org/ tropics, such as steppes, semi-desert, and desert, cancer. It grows mainly in arid and semiarid cli- 10.1055/s-0031-1298453 are forced to collect and store water to survive mates, although, this plant, as well as Aloe arbor- Published online April 19, 2012 long, dry periods. Aloe plants have long been the escens and other aloes are found also in non-arid Planta Med 2012; 78: 843–852 source of important products due to their nutri- countries like Greece, Italy, and Japan. Naturalized © Georg Thieme Verlag KG Stuttgart · New York · tional and therapeutic values, their leaf exudates stands of the species occur in the southern half of ISSN 0032‑0943 being used to a great extent in traditional medi- the Arabian peninsula, throughout North Africa cine [3]. (Morocco, Mauritania, and Egypt), Sudan, and Correspondence Eli Harlev Aloe plants exhibit anticancer activity in vitro neighboring countries, and in the Canary, Cape Institute of Evolution and Inter- (l" Table 1)andin vivo (l" Table 2). Their antineo- Verde, and Madeira Islands. The species is fre- national Graduate Center of plastic property is due to at least three different quently cited as being used in herbal medicine, Evolution University of Haifa mechanisms based on antiproliferative, immu- such as in treating wounds and burns, but also Mount Carmel nostimulatory, and antioxidant effects. The anti- diabetes and elevated blood lipids in humans [5]. Haifa 31905 proliferative action is determined by anthracenic These effects are attributed to compounds, such Israel Phone: + 972899565713 and anthtraquinonic molecules, such as aloe- as polysaccharides, mannans, anthraquinones, [email protected] emodin, aloesin, and aloin (also called barbaloin) and lectins, present in the Aloe leavesʼ gel. Harlev E et al. Anticancer Potential of… Planta Med 2012; 78: 843–852 844 Reviews Fig. 1 The two mostly used Aloe plants in cancer research and therapy, Aloe vera (A)andAloe arbor- escens (B). Fig. 2 Chemical structures of acemannan (1), aloin (2), aloe-emodin (3), and aloesin (4). The purpose of this article is to review the work performed up- work located in the scientific literature adding new information to-date on the application of extracts and isolated components has been incorporated into the manuscript, while concentrating derived from plants of the Aloe genus in cancer research. To the on the essence and ignoring experimental details. Major key best of our knowledge this attempt is a first of its kind. The article words used: cancer, anticancer, Aloe, Aloe vera, Aloe arborescence, This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. is divided into subsections, each focused on the various anti- Aloe saponaria in various combinations. cancer attributes of a major bioactive component contained in the Aloe leaf. Acemannan ! Search Methodology In vitro studies ! Many studies of the immunological effects of extracts from plants The purpose of this review has been to display before the inter- of Aloe have focused on the clear mesophyll gel of the Aloe vera ested reader a broad view of the research work performed up- leaf and on its major storage carbohydrate, acetylated mannan, to-date on the subject. For that end, the scientific search engine acemannan (l" Fig. 2). Acemannan is the name given to the major “SciFinder” was found to be an extremely usefull tool, as it re- carbohydrate fraction, a polysaccharide, or a mixture of polysac- trieves information from both MEDLINE and CAPLUS data bases. charides, obtained from the gel of the Aloe vera leaf. Acemannan In most cases the whole papers were obtained and carefully gone is known to have diverse biological activities, including immuno- through. In few cases only the abstract could be obtained. As the modulatory and antitumor attributes [6]. amount of work performed on the subject is not very large, any Harlev E et al. Anticancer Potential of… Planta Med 2012; 78: 843–852 Reviews 845 Table 1 In vitro anticancer effects of components included in the Aloe leaf. Compound Plant Cellular effects Mechanism Conc. Reference Acemannan Aloe vera Produced cell morphology changes in Immunomodulatory 100 µg/mL Zhang and mouse macrophage cell line (RAW activities Tizard, 1996 [4] 264.7 cells) Aloe vera Inhibited [3H]B[a]P‑DNA adduct for- 0.4–250 µg/mL Kim and Lee, mation in primary rat hepatocytes 1997 [7] treated with [3H]B[a]P Aloe saponaria Exhibited antiproliferative effect on 0.6 mg/mL (IC50) Sampedro et al., and Aloe vera human and mouse cultures of T lym- 2004 [9] phocites Aloe vera Induced tumor cell cytotoxicity in Murine macrophage stimu- 500 µg/mL Liu et al., 2006 murine peritoneal macrophage cells lation [12] Aloin Aloe vera Showed antiproliferative effect in He- ↑Apoptosis 97 μM (IC50) Niciforovic et al., LaS3 human cervix carcinoma cells 2007 [16] Not specified Exhibited cytotoxic activity against ↑Apoptosis, ↓topoisomer- 60 µg/mL (MCF-7); Esmat et al., 2006 two human breast cancer cell lines ase type IIA, ↓cyclin B1 80 and 150 μg/mL [18] (MCF-7 and SKBR-3) (SKBR-3) Aloe-emodin Aloe vera Produced reproducible antitumor 29 µM (IC50, K562); Grimaudo et al., effects in human K562 leukemia cell 10.5 µM (IC50, 1997 [25] line K562/R) Induced cytotoxicity in human colon ↓Apoptosis, ↓casein kinase 0.37 mM Lin and Uen, carcinoma cell lines (DLD-1 and II, ↑cyt. c, ↑caspase-3 acti- 2010 [26] WiDr) vation Not specified Reduced cytotoxicity of TNF-α ↑Autophagy, ↓ERK activa- 5–120 µM Harhaji et al., towards L929 mouse fibrosarcoma tion 2007 [27] and U251 human glioma cell lines Aloe vera Displayed a long-term antiprolifera- ↓PKC, ↓c-myc 40 µM Guo et al., 2008 tion effect in human gastric cancer [28] MGC-803 and SGC-7901 cells Not specified Inhibited the viability of T24 human ↑p53, ↑p21, ↑Bax, ↑Fas/ 50 µM Lin et al., 2006 bladder cancer cells APO‑1, ↑caspase-3 [29] Aloe vera Decreased cell proliferation in trans- ↓S phase progression, 40 µM Acevedo-Duncan formed glia (SVG) and human glioma ↓PKC activity et al., 2004 [24] U-373MG cell line (U-373MG) Not specified Differentiated surviving cells toward Formation of intracytoplas- 40 µM Mijatovic et al., the astrocytic lineage and exhibited mic acidic vesicles, ↓ERK1/2 2005 [30] autophagic cell death in rat C6 glioma cell line Not specified Caused cell death in human lung ↑caspase-3, ↑caspase-8, 50 µM Lee et al., 2001 squamous cell carcinoma cell line ↑caspase-9, ↑Bax, ↑Fas [31] (CH27) Not specified Inhibited cell proliferation in human ↑Apoptosis,↑p53, ↑p21 10 and 20 µg/mL Kuo et al., 2002 liver cancer cell lines (HepG2 and Hep G1 arrest [32] 3B) Not specified Induced cytotoxicity in human lung ↑Apoptosis, modulation of 40 µM Yeh et al., 2003 non-small cell carcinoma cell line cAMP-dependent protein ki- [33] H460 nase, PKC, Bcl-2, caspase-3, and p38 protein expression Not specified Inhibited growth of metastatic lesion Not specified Wasserman et al., of Merkel cell carcinoma (MCC) cells 2002 [34] This document was downloaded for personal use only.
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