Cancer is a general term applied to abnormal growth of cells that starts to grow and propagate through uncontrolled cell division and gradually expand throughout body and finally lead to death by invading and destroying normal cells [1-3]. Skin cancer is the most common of all the cancers that affecting peoples due to exposure to uncontrolled ultra violet radiation [4]. Carcinogenic infections are also one of an important cause of cancer, particularly in less developed countries. In 2008, 32.7% of sub-Saharan Africa were affected by cancer through uncontrolled carcinogenic infections [2,5]. According to the World Health Organization (WHO), cancer represents noncommunicable diseases responsible for 63% of deaths worldwide, where it is characterized as the second cause of death after cardiovascular disease and was responsible for the death of 7.6 million people in 2005, 12.7 million new cancer cases in 2008, about 14 million new cases and 8 million cancer-related deaths in 2012 [6-10]. However, its severity will be expected to increase to 75 million prevalent cases, 27 million incident cases and 17 million cancer-related deaths by 2030 [9,10].

Recently, Ethiopia is one of the developing countries which are seriously affected by cancer and it has been reported that cancer death accounts for about 4% of all death [11,12]. Only about 15% of all cancers may be inherited from genetic defects and the rest are strongly affected by environmental risk factors such as exposure to ultraviolet ray, aging, diet, lifestyle, smoking cigarette and exposure to harmful substances [13]. So far, cancer treatment is based on surgery, radiotherapy and chemotherapy. But only 50% of the cancer patients are capable of curing and the rest may have only prolonged survival or even no benefit at all from the treatment and the success of drug therapy is still far from achievement. To overcome this serious problem, a lot of mechanism has been designed to synthesis a potential full anticancer drug. Many hundreds of chemical variants of known class of cancer chemotherapeutic agents have been synthesized but it is not still successfully achieved due to its more side effects. Some recent surveys confirmed that more than 60% of cancer patients use vitamins or herbs as therapy [1]. A successful anticancer drug should kill selectively abnormal or affected cells without excessive damage to normal cells [2,3]. Hence, medicinal plants continue to play an important role in the healthcare system of a large number of the world’s population.

Despite the remarkable advancements of the modern medicine, the traditional system of medicine (TSM) still serves as a potential primary health care modality in developing countries. The recent reports suggest that there is a renewed interest has been observed towards TSM even in the developed countries too, because of acute side effects of chemotherapy and radiotherapy can occasionally be life threatening and may affect patient compliance in addition to generating vulnerability to the adoption of herbal medicines use which promise cure [14-16].

According to world health organization, traditional medicine (TM) is the sum total of the knowledge, skills and practices based on the theories, beliefs and experiences indigenous to different cultures and nations. It is used in the maintenance of health, prevention, diagnosis, or treatment of disorders. Traditional medicine is popular in the developing world and its use is rapidly spreading in the developed nations. The World Health Organization (WHO) estimates that 80% of Asian and African populations rely on traditional medicine for their primary health care needs and in the developed countries 70%-80% of the population use some form of complementary and alternative medicine at some stage. In Ethiopia, there is a long history of using medicinal plants to treat a variety of diseases and up to 80% of the population uses it due to the cultural acceptability of healers, local pharmacopeias, the relatively low cost and difficult access to modern health facilities [16-22].

Traditionally, it has been believed that using fruit and leaves from trees/herbs have better potential to heal patients suffering from cancer diseases than modern medicines. Because, these traditional medicinal plants may possess secondary metabolites like polyphenols, terpenes and alkaloids which has anti-mutagenic and anticancer properties. The specific plants to be used and the methods of application for particular ailments were passed down through oral history. Eventually information regarding medicinal plants was recorded in herbals. Right from its beginning, the documentation of traditional knowledge, especially on the medicinal uses of plants, has provided many important drugs of modern day. These traditional medicines initially took in the form of crude drugs such as tinctures, teas, poultices, powders, and other herbal formulations [20,23,24]. Even though many plants/herbs used as a medicine for varies diseases including cancer, still it lacks scientific evidence for its therapeutic potential as anticancer agent.

The aim of this review is to collect available data about the cancer therapy of medicinal plants/herbs so far studied by ethnobotanical surveys and scientifically studied in Ethiopia. The information was obtained from scientific research engines Google Scholar between 2000 and 2017.

The ethnobotanical surveys were conducted in different regional state of Ethiopia country. Several commonly used plants/herbs have been identified by different ethnobotanical surveys as possessing cancer-preventive properties. These include members of various species as mentioned in Table 1 below. Table 1 shows part of the plant/ herb used, type of cancer, method of application and therapy type. It includes experimentally studied traditional medicinal plants used by traditional healers in Ethiopia for cancer therapy.

Table 1: Plants/herbs used by traditional healers for cancer therapy in Ethiopia.

Even though many plants/herbs have been used by traditional healers of Ethiopian society, many species do not have scientific evidence of their anticancer activity. Out of 65 plants/herbs reviewed in this study, only 30 plants/herbs have been scientifically studied by different researchers at different times for its medicinal value against different types of cancer diseases. As reviewed in Table 1, some plants/ herbs are traditionally in use at community level but not scientifically studied even though it has promise in future to be used as anticancer.

Aerva javanica

Aerva javanica is a species of prostrate shrub belonging to the Amaranthaceae family. It is widely distributed in much of tropical Africa, and in the south and south-west of Asia. The plant is deep rooted and used as a soil binder in desert reclamation [12,25].

In Ethiopia, peoples of different religious and ethical group use A. javanica as traditional medicine to treat various diseases including cancer [12,26]. The root powder mixed with bat’s blood is taken orally early morning before breakfast to treat breast cancer [26]. Scientifically supported study has been reported that the leaf extracts of A. javanica showed antiproliferative effect on human breast cancer cell lines (MCF-7). In addition to this, more purified leaf extracts of another species of A. lanata genus also showed anticancer, as well as apoptotic activities against different cancer cell lines [12,27].

Annona muricata L.

Annona muricata L. is a small, much branched, perennial tree of Annonaceae family of which is a typical tropical tree with heart shaped edible fruits and widely distributed in most of the tropical countries. Its fruit has been used in traditional medicine in many countries as antiviral, antinociceptive, anti-inflammatory and antihyperglycemic properties. It is also effective against multidrug resistant cancer cell line. It has been demonstrated that leaf extracts of A. muricata possess significant anticancer potentials in human cancerous cells [37].

Annona reticulata L.

Annona reticulata L. is referred as bullock's heart, which is a slender semi-deciduous tree is belonging to Annonaceae family and widely distributed throughout Ethiopia [37,38]. Traditionally peoples have been used A. reticulata as insecticides, anthelmintic and are also used externally as suppurate. Experimentally, it has been reported that the ethanol extract of roots showed the presence of antiproliferative activity against cancer cell lines in vitro [37,39].

Annona squamosa L.

Annona squamosa L. known as custard apple, is a family of Annonaceae. It is widely used as traditional medicine in different cultural religious for treating various diseases including antitumor [37,40]. It has been supported with scientific evidence that squamosin which is isolated from A. squamosa , inhibited proliferation of HL-60 cells and induced apoptosis by the activation of caspase-3. Ascimicin and acetogenin also exhibited cytotoxic activity against different tumor cells [37,41].

Asparagus racemosus

Asparagus racemosus is species which is belonging to Asparagaceae family. In addition to its traditional medicinal value, it has been documented that asparagamine A which is isolated from A. racemosus showed antitumor activity [12].

Asparagus africanus

Asparagus africanus is a species of climbing plant in the family of Asparagaceae [29]. In the practice of Ethiopian traditional medicine, it has been used to treat many diseases including uterine prolapse and breast tumor [12,29]. The roots of the plant have been reported to be used for tumor treatment. Of the compounds isolated from A.africanus , gallic acid has been demonstrated to display antineoplastic properties [12].

Bersama abyssinica

Bersama abyssinica is a species belonging to Melianthaceae family and traditionally treat tumor using chewing stem peelings [42]. The fresh roots are pounded and juices [43], infusion prepared from the bark (from stem) were administered to treat some forms of tumor [12]. It has been investigated that bufadienolides-cardiac glycosides compound which was isolated from B. abyssinica showed antitumor activity [42]. Hallebergenin-3-acetate and lignin have been isolated and shown to inhibit tumor and certain form of carcinoma respectively [12].

Crinum abyssinicum

Crinum abyssinicum is a species of bulbous plant belongs to Amaryllidaceae family and believed to be native to Ethiopia [44]. Traditionally, the leaves of C. abyssinicum have been reported to be used in Ethiopia as a remedy for some forms of tumor [12,34]. The leaf powder mixed with hyena feces and latex applies topically on the affected area and gets relief gradually [26]. It has been scientifically demonstrated that C. abyssinicum contain the compounds like lycorine, crimine, narciclasine, 3-epihalmanthidine, crinamine, lycobetaine, precriwelline, crinamide, crinafolidine, criasbetaine, crinasiadine, crinasiatine and crotepoxide, all with antitumor/ anticancer properties [12].

Cucumis prophetarum/ficifolius

Cucumis prophetarum is a species of tendril bearing herb of Cucurbitaceae family [29]. It is widely grown in Africa, Asia, Australia and Ethiopia [12]. C. prophetarum has been used as traditional medicinal plants by community of Oromo in Ethiopia to treat various human ailments including skin cancer. As reported on different ethnobotanical survey, pulverized roots made as pastes/ointments are applied topically on affected areas. In consistent with the traditional use of this plant, scientific studies have also demonstrated potent antineoplastic activity for some compounds of tetracyclic triterpenes isolated from the fruits of the plant [12,29]. The same to this, compounds cucurbitacin D and E obtained from C. ficifolius showed potent cytotoxic and antineoplastic agents [12].

Dorstenia barnimiana

Dorstenia barnimiana is a perennial monoecious herb of Moraceae family and it is more unique to East Africa including Ethiopia [12,45]. It is one of the most known traditional medicinal plants in Ethiopia to treat various human ailments including external cancer/tumor visible on the surface of body [12,34]. The powder of areal parts made in to paste with butter and applied topically to treat hemorrhoid-cancer [33]. Making small opening at affected part and inserting in the opening with fresh or dry root is one of the methods used to treat cancer [26,34]. For cancer treatment, the tuber of the plant is directly applied on the affected area. Experimentally, it has been confirmed that styrene is one of the compounds isolated from the tubers of D. barnimiana and demonstrated anticancer activity [12,46].

Eucalyptus globulus

Eucalyptus globulus is a species of Fabaceae family. The Sidama communities of Ethiopia are traditionally use E. globules leave to rub on skin to reduce fever and use the boiled leave of a mixture of Eucalyptus and ‘’Damakasse’’ in water to treat common cold. But the scientific study shows that borneol and euglobal-III are compounds isolated from hexane extracts were reported as antitumor, anthelmintic and antihistaminic activity [42,47].

Euphorbia tirucalli

Euphorbia tirucalli is a plant species in the family of Euphorbiaceae and widely distributed in Africa, prominently in the northeastern part of the continent that includes Ethiopia [12]. E. tirucalli produces milky vesicant/poisonous latex that partially contributes to its medicinal value. Traditionally, the powder of the roots and/or latex has been used in Ethiopian communities for treatment of different forms of tumors/ cancers and other diseases. Experimentally, alcoholic and aqueous extracts of the stems of E. tirucalli have been shown significant activity against adenocarcinoma and sarcoma. The esters of the tetracyclic diterpenol phorbol found in the plant act as tumor inhibitors. However, even though E. tirucalli has been promoted and traditionally used as an anticancer agent, under certain circumstances it also suppresses the immune system and promotes tumor growth [12,29]. So, it needs further investigation to confirm whether it has good anticancer activity or not in order to help the community so far use it.

Gindia involucrate

Gindia involucrate is a perennial herb of Thymelaeaceae family [12]. In Ethiopia, G. involucrate is used as traditional medicine for treatment of malaria and breast cancer/tumor. The root part is used for cancer treatment. In consistence with traditional value of this plant, it was experimentally proved the anticancer activities of diterpenes, gnidicin, gnididin, gniditrin, gnidiglucin, gnidilatidin and mezerein compounds isolated from G. involucrate against cancer cell models [12,29].

Gloriosa superba

Gloriosa superba is a species of perennial trailing/climbing herb belonging to the family Liliaceae [42]. Traditionally, the root part of this plant has been used for the treatment of breast cancer in Ethiopian societies. First, the root part was chewed and applies externally on the affected breast and then get relieve [12,29,34]. Experimentally, it has been reported that alkaloid colchicines which is a well-known antineoplastic compound was isolated from root of G. superb [12,29].

Jatropha curcas

Jatropha curcas is a species of flowering plant belonging to Euphorbiaceae family [12]. J. curcas has been used as traditional medicinal plants for the treatment of various diseases including inhibiting some forms of tumor. A paste made from seed powder of the plant with honey is used in the treatment of tumor. In consistence with its traditional value, the extracts of the plant showed significant inhibition against P388 lymphocytic leukemia both in vitro and in vivo . Triterpenes: α-amyrin and taraxerol; the diterpenes: jatrphol, jatropholone A, B and phorbols are compounds isolated from this plant and showed significant antitumor activities [12,29].

Kalanchoe petitiana

Kalanchoe petitiana is a species of a succulent plant that belongs to the Crassulaceae family [12,48]. In Ethiopia, the leave part of K. petitiana has been used as traditional medicine to treat many diseases including breast tumor and skin cancer [12,29]. Gallic acid which was isolated from leaves of K. petitiana showed significant antitumor activity which confirms the traditional value of the plant [12,29,49].

Lagenaria sicararia

Lagenaria sicararia is a species of climbing plant that belongs to the Cucurbitaceae family [12]. Traditionally, the leaves are crushed and squeezed onto the affected area and relieve from cancerous sores [12,21,29]. In consistence with its traditional value, alcoholic extracts of some triterpinoid compounds isolated from the stems and fruits of L. sicararia exhibited significant cytotoxicity and anticancer activities against SKHIP1 cell line and human breast carcinoma cell line (MCF-7) [12].

Maesa lanceolata

Maesa lanceolata is a species belongs to the Myrsinaceae family and is a shrub widely distributed throughout countries in Central Africa, including Ethiopia and Kenya. It’s all parts (flowers, leaves, stem, bark, seeds, and roots) has been used as traditional medicinal plants to treat different human ailments but not known its use as anticancer. Experimentally, the quercetin-3-O rhamnose compound isolated from methanolic extracts of seeds of M. lanceolata showed significant antitumor activity against HCT116 cells [44].

Maytenus senegalensis

Maytenus senegalensis is a shrub species belonging to Celastraceae family [12]. In the community of Ethiopia, traditional medicinal plants/herbs are widely used for the remedial solution of different human ailments. As reports of ethnobotanical surveys indicates, M. senegalensis is used to treat cancer [12,50]. Ansamacrolide which was isolated from M. senegalensis showed significant inhibition against tumor in mice but, like the quassinoids from B. antidysenterica , did not show sufficient activity in phase 2 clinical trials [12].

Otostegia integrifolia

Otostegia integrifolia is an herbaceous plant belongs to Lamiaceae family [14,51]. Some research has been indicated that stigmasterol which is one of the chemical constituents of O. integrifolia showed to some extent anticancer activities against certain cancers, including ovarian, prostate, breast and colon cancers [14,52]. Its traditional use for the treatment of cancer is not yet known.

Plambago zeylanicum

Plambago zeylanicum is a species of evergreen shrub with long tuberous roots and straight stems belongs to the Plumbaginaceae family [53]. It is used in Ethiopian traditional medicine for the treatment of different types of diseases, including cancer/tumor [12,34,54]. The juicy product of squeezed fresh leaves is taken orally to treat cancer/tumor. In consistence with its traditional value, chitranone, isozeylanicone, zeylanicone, elliptinone, droserone and plumbagin were isolated from P. zeylanicum have shown anticancer activities. Of the compounds mentioned above, plumbagin which is a class of quinoid inhibit tumor by controlling hormone-refractory invasive prostate cancer (PC-3, LNCaP, and C4-2) [12,53,55-58] with apoptosis induction, which was accompanied by ROS generation and depletion of intracellular GSH levels [55-58]. It is also strong enough to inhibit molecular targets such as PKC, STAT-3, AKT and PI-3K [12]. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent. Plumbagin enhances TRAIL-mediated apoptosis through up-regulation of death receptor in human melanoma A375 Cells. It activates ERK1/2 and inhibits Akt activity in cancer cells. It activates NAD(P)H oxidase, Src, and PI3K and that the activated PI3K or PDK1 subsequently stimulate Akt and Ras–Raf– MEK1/2–ERK1/2 in 3T3-L1 cells. The antiproliferative and apoptotic activity of plumbagin by using two human colonic cancer cell lines, HT29 and HCT15 showed the IC50 of plumbagin for HCT15 and HT29 cells (22.5 μM and 62.5 μM, respectively) were significantly different through activation of NFκB, Caspases-3, elevated levels of TNF-α, cytosolic Cytochrome C were seen in both HCT15 cells HT29 treated with plumbagin, aberrant apoptosis with decreased level of pEGFR, pAkt, pGsk-3β, PCNA and Cyclin D1 was observed only in 15 μM and 30 μM plumbagin treated HCT15 and 75 μM plumbagin treated HT29 cells. It has been used to inhibit ultraviolet radiation (UVR)-induced development of squamous cell carcinomas (SCC). It (5-20 μmol/L) induces apoptosis of SGC-7901 cells and potentiated the sensitivity of SGC-7901 cells to chemotherapeutic agent TNF-α and cisplatin. The naphthoquinones, juglone and plumbagin could be promising chemopreventive agents for human intestinal neoplasia [55-58]. Ethanolic extract of root has anticancer activity against male Swiss albino mice and Wistar albino rats induced with cancer [53,59].

Prunus africana

Prunus africana is an evergreen tree belongs to Rosaceae family [12]. Traditionally, the root of P. africana is used to treat a number of diseases including cancer. In addition to its traditional medicinal value, tenuifolin and ferulic acid those were isolated from the roots and leaves of P. africana have been demonstrated antineoplastic properties [12,29].

Rumex abyssinicus

Rumex abyssinicus is a perennial weed plant in the family Polygonaceae. Traditionally, Ethiopian women use the roots of the plant as cosmetic to beauty their palms hands and feet. Like others traditional medicinal plants, its roots also used for treating various types of diseases including breast cancer. The literature report shown that the anticancer activity of the crude extracts of the roots of R.abyssinicus seen against tumor cell lines of prostate, brain, breast and in leukemia cell cultures [12].

Solanum nigrum

Solanum nigrum is a species of perennial shrub belongs to the Solanaceae family [29]. The different parts (leaves, roots and stem) of S. nigrum are reported to be used as both food and medicinal plants in different rural communities of Ethiopia. It has been used as medicinal plant for the treatment of cancerous sores [12,31,60]. In support with its anticancer effects, experimentally the leaves of the plant have shown significant inhibition against growth of cervical carcinoma in mice. S. nigrum and other species in the genus have been shown to contain the compound solasodine which has potent antineoplastic activity and supporting at least the claimed anticancer activity of the plants used in Ethiopia [12,29]. Acetic acid, solanine, solanidine are some of the isolated compounds from leave part of S. nigrum showed significant antioxidant, hepatoprotective, anti-tumor cytostatic and anticonvulsant [42,61].

Verbascum sinaiticum

Verbascum sinaiticum is a perennial plant species belongs to Scrophulariaceae family [12]. As a traditional medicinal plant, the community of Ethiopia uses the root part of V. sinaiticum for different types of diseases including tumor. In consistent with the reported use of V. sinaiticum as antitumor, the bioactive compound sinaitiein has been isolated with proven anticancer activity against breast and prostate cancer cells [12,29].

Vernonia amygdalina

Vernonia amygdalina is a species of relatively small plants belongs to Compositae family [12]. As a traditional medicinal plant, different parts of V. amygdalina are used in Ethiopia for relieving from cancer/ tumor. In agreement with its traditional value, vernoid and vernomygdin were isolated from V. amygdalina and shown inhibition of carcinoma cells of nasopharynx in vitro . Another compound identified as verlnolepin was also reported to act as cytotoxic as well as antitumor against Walker 256 carcinosarcoma in a rat model [12,29]. Sequiterpene lactones, flavonoids (luteolin), coumarins and phenolic acids are among the cancer chemoprevention, free radical scavenging and induce detoxification compounds isolated from leaves and tender shoots of V. amygdalina [42,62].

Withania somenifera

Withania somnifera is a shrub species belongs to Solanaceae family [12]. It is Ethiopian traditional plants used to treat different ailments including tumor/swelling. It is experimentally supported that the crude extract as well as compounds (withaferin A and withanolides) isolated from W. somnifera shown antitumor properties against animal and cell culture models [12,29].

Zingiber officinale

Zingiber officinale is a species herbal plants belonging to Zingiberaceae family. It is traditionally used as spice and used for motion sickness and gastrointestinal distress. Experimentally, some compounds such as monoterpenoids: gingerols and shogaols are among the isolated compounds from Z. officinale act as immuno-modulatory, antitumorigenic, anti-inflammatory and antiapoptotic [42,63].

Ethiopia is one of the developing countries which is seriously affected by cancer and it has been reported that cancer death accounts for about 4% of all death. To overcome this serious problem, about 80% of the population uses traditional medicine due to the cultural acceptability of healers and local pharmacopeias, the relatively low cost and difficult access to modern health facilities. Traditionally, it has been believed that using fruit and leaves from trees/herbs have better potential to heal patients suffering from cancer diseases than modern medicines.

This review shows the therapeutic potential of many traditional medicinal plants/herbs that can be used as anticancer agents in future. The extensive study on the anticancer activity of traditional medicinal plants/herbs in Ethiopia highlighted their potential for future chemotherapeutic agents, especially Annona muricata, Bersama abyssinica, Crinum abyssinicum, Eucalyptus globules, Euphorbia tirucalli, Gindia involucrate, Jatropha curcas, Maesa lanceolata, Plambago zeylanicum, Prunus Africana and Vernonia amygdalina are among the species which have more phytochemical constituents that showed anticancer properties at in vitro stage. Even though many plants/herbs have been used by traditional healers of Ethiopian society, many species still do not have scientific evidence of their anticancer activity. So, it needs scientific study to know whether it has therapeutic potential for cancer treatment or not. In addition to in vitro analysis, it needs further investigation at in vivo and in clinical trials to know its anticancer potential more for future use. Furthermore, it needs better knowledge and skills on the mechanism of action in order to establish rational phototherapeutic approaches.