Mini Reviews 1203 Medicinal Plants from Jordan in the Treatment of Cancer: Traditional Uses vs. In vitro and In Vivo Evaluations – Part 1 Authors Fatma U. Afifi-Yazar, Violet Kasabri, Rana Abu-Dahab Affiliation Faculty of Pharmacy, University of Jordan, Amman, Jordan Key words Abstract stituents are listed. Studies of random screening l" traditional medicine ! for selective cytotoxicity and antiproliferative ac- l" medicinal plants Plant species have long been used as principal in- tivity of local spices, domesticated greens, or wild l" cancer gredients in traditional medicine. Different sur- plants are briefly discussed. Recommended future l" Jordan veys showed that ethnomedicinal plant species directives for the design and conduct of compre- used by the inhabitants of Jordan for the treat- hensive trials are pointed out to validate the use- ment of cancer are inadequately screened for fulness of these active plants or bioactive phyto- their therapeutic/chemopreventive potential and constituents either alone or in combination with phytochemical findings. In this mini review, tra- existing therapies or complementing pharmacol- ditional herbal medicines pursued indigenously ogies. with their methods of preparation and active con- Introduction their national conservation and sustainability ! [18]. The Hashemite Kingdom of Jordanʼs habitat is In a survey carried out with the herbalists in Jor- unique in that the intersection of dense forest, dan, none of the interviewed herbalists men- arid desert, and tropical geography endows the tioned any plants for the treatment of cancer country with a rich variety of plants and microor- [15]. On the other hand, literature surveys based ganisms that can be studied efficiently in a rela- on the published studies indicated that in Jordan tively small land area (l" Fig. 1) [1]. More than and in the neighboring countries, 27 plant species received January 13, 2011 2500 wild plant species from 700 genera exist; of are considered as traditional remedies for the revised January 28, 2011 these, there are approximately 100 endemic spe- treatment of the different types of cancers [14, accepted February 2, 2011 cies, 250 rare species, and 125 very rare species 19–23]. This article summarizes information on Bibliography [1–3]. In the Mediterranean basin, there seems to different aspects of chemopreventive-therapeutic DOI http://dx.doi.org/ be a wealth of ethnobotanical studies providing a plants as well as randomly screened plants for the 10.1055/s-0030-1270832 new and key tool for a quest after invaluable phy- antiproliferative activity to stimulate interest in Published online February 23, 2011 topharmaceuticals or the development of func- these herbs which are of importance in Jordan Planta Med 2011; 77: tional foods or nutraceuticals [4–12]. Traditional and other countries of the semi-arid tropics. 1203–1209 © Georg Thieme medicine practices are part of the Jordanian cul- Verlag KG Stuttgart · New York · ture. Despite modern medicine accessibility, ISSN 0032‑0943 herbal medicine has often maintained popularity Results and Discussion Correspondence [13]. The percentage of reliability on herbal med- ! Prof. Dr. Fatma U. Afifi-Yazar icine varies from rural and desert areas to urban Cancer is a leading cause of death worldwide. Department – of Pharmaceutical Sciences ones [14 16]. Crucially, the folk phytotherapy is More than 70% of all cancer deaths occurred in Faculty of Pharmacy “aging” or “vanishing” in the sense that knowl- low- and middle-income countries. Deaths from University of Jordan edge of medicinal plants persists mainly in elderly cancer worldwide are projected to continue ris- Queen Rania Al-Abdullah Street Amman 11942 rural people with little schooling [17]. In the last ing, with an estimated 12 million deaths in 2030 Jordan decades negative human impacts also affected [24]. Phone: + 96265355000 the ecosystem, adding more plants to the list of Running second after heart diseases, cancer is a ext. 23301 Fax: + 962 65300250 endangered species, thus calling on the urgent major cause of morbidity among the Jordanian [email protected] need for community-based programs promoting population, with an estimated incidence rate of Afifi-Yazar FU et al. Medicinal Plants from… Planta Med 2011; 77: 1203–1209 1204 Mini Reviews dominica, Conyza canadiensis and Achillea santolina, I. viscosa, Lavendula officinalis,andS. syriaca showed promising and potent antiproliferative activities on a breast cancer cell line (MCF-7) [27–29]. The most active plant was I. graveolens with an IC50 of 3.83 µg/mL [27]. Inclusive reporting of the selective cytotoxicity of Rhus coriera and A. biberstenii along with the preceding seven species were collectively presented at the 1st Annual World Can- cer Congress 2008 Shanghai, China. The ethanol extracts of the active plants were further evaluated using T47D, ZR-75-1, and BT474 cell lines, as were some of their volatile fractions and iso- lated pure flavonoids [28]. Al-Kalaldeh et al. demonstrated the cytotoxicity activity for the ethanol extracts of Origanum syriacum (IC50 of 6.4 µg/mL), Laurus nobilis (IC50 of 24.5 µg/mL), and S. triloba (IC50 of 25.3 µg/mL) against MCF-7 cell lines [30]. These were among many other commonly used culinary spices or edible domesticated greens proven for their therapeutic properties [31]. In a parallel line of work, Faris et al. illustrated the enhanced chemopreventive effect of cooked lentils against colorectal carcinogenesis [32]. Further- more, compared to garlic-only treatment, combined supplemen- tation of soy and garlic had a marked modulation of 7,12 dimeth- Fig. 1 Biogeographic zones of Jordan. ylbenzy-α-anthracene induced mammary cancer in female albi- no rats [33]. Additionally, aqueous extracts of Nigella sativum, Al- lium sativum,andOnopordum acanthium augmented signifi- cantly splenic natural killersʼ cytotoxicity against tumor targets 5000 new cases per year. Male to female ratio for cancer cases in in vitro and in vivo [34–36]. Jordan is 0.97:1. The overall median age of cancer diagnosis in Few more reports on selective evaluation of the traditionally Jordan is 56 years (males: 60 years; females: 52 years). 43.15% used plants for their cytotoxicity activities were obtainable [23, of all newly registered cases occurred in the age of 60 years and 37,38]. Talib and Mahasneh screened 16 plants for their antipro- above, and 11.6% occurred below the age of 30 years [25]. liferative activity against Hep-2, MCF-7, and Vero cell lines and As recently updated by the Jordan National Cancer Registry demonstrated that methanol fractions of Ononis hirta and I. vis- (JNCR) statistics, the most commonly diagnosed cancers in a de- cosa exerted their antiproliferative activity by inducing apoptosis scending order in 2008 would be breast (18.8%), colon (7.7%), in cancer cell lines [23]. In vitro antiproliferative activities of sev- lung (7.7%), bladder (4.3%), and non-Hodgkinʼs lymphoma eral Salvia species against different cancer cell lines were tested (4.8%) [25,26]. by Fiore et al. [37]. Their findings showed promising cytotoxic ac- The evidence-based practices of consuming plants and plant de- tivity for S. menthefolia, S. spinosa, S. sclarea,andS. dominica [37]. rived products in the treatment of cancer with the orthodox ther- In a panel of fibrosarcoma L929sA cells, breast cancer cells MDA- apy were first reported by Afifi et al. [13]. In cooperation with the MB231 and MCF-7, organic extracts of Withania somnifera, Psidi- King Hussein Cancer Centre (KHCC), the researchers interviewed um guajava, L. nobilis,andS. fruticosa also displayed remarkable a total of 1138 randomly selected cancer outpatients, predomi- antitumor cytotoxicity [38]. Withaferin A, a major constituent of nantly Jordanians. Among interviewees, the total number of com- W. somnifera, was further characterized among a novel class of plementary and alternative medicine (CAM) users was 404 NF-κB inhibitors, holding promise in cancer treatment [39]. As (35.5%). All CAM users were either on chemotherapy or radio- part of serial studies on the unique and under-explored biodiver- therapy and preferred to use the crude extract in the form of in- sity of Jordan, the colchicinoids of Colchicum spp. (Colchicaceae) fusions (n = 296, 73.3%) [13]. Crude extracts were prepared from were pursued [40–44]. Alkaloids of the colchicinoid structural coarsely powdered plant mixtures and none of the individual class are well known from this genus, particularly (−)-colchicine, plants could be identified by the researchers. Therefore emphasis and these compounds have been investigated extensively for is given in the present review to the plants with claimed anti- both toxicological and potential medical properties, exhibiting cancer activities in the ethnopharmacological studies and to the potent cytotoxicity against a human cancer cell panel [45]. Never- findings of the random screening of the plant species from the lo- theless, the pyrrolizidine alkaloids recovered from Echium glom- cal flora for their antiproliferative activities. l" Table 1 lists the eratum (Boraginaceae) by the same research group lacked any ethnopharmacologically promoted plants with the method of anticancerous cytotoxicity [46]. preparation; parts used and reported phytochemical constitu- Nowadays, it is well accepted that plant constituents possess can- ents. Clearly, in half of them, experimental studies to prove their cer-preventive and cancer-therapeutic activities and natural cytotoxicity properties, however