**4.3 Asteraceae—***Eclipta prostrata* **(L.) L.**

The false daisy *E. prostrata*, also known as *E. alba* (L.) Hassk. or *E. erecta* L. (**Figure 4**), is probably native to either Asia or the Americas but is now commonly encountered in subtropical and tropical regions throughout the world. It has become an invasive weed in many parts of the tropics, which is particularly due to its ability to grow fast and flower early. The tender leaves and young shoots are consumed as a vegetable but may also serve as a source for the synthesis of titanium dioxide nanoparticles (nano-TiO2) [80]. Nano-TiO2 is widely employed to provide whiteness and opacity to paints, plastics, papers, inks, food colorants, and toothpastes; for the production of cosmetics and skin care products such as sun blocks because of its ability to protect the skin from UV rays while remaining transparent on the skin; and as an additive in antifogging coatings and self-cleaning windows because of its photocatalytic sterilizing properties [81].

**Figure 4.**  *The false daisy Eclipta prostrata (L.) (Asteraceae) (from: https://goo.gl/images/YGw37Z).* 

*Anticancer Activity of Uncommon Medicinal Plants from the Republic of Suriname: Traditional… DOI: http://dx.doi.org/10.5772/intechopen.82280* 

 *E. prostrata* is an important herb in Indian traditional medicine and is used for treating a host of conditions such as skin wounds and certain skin disorders; toothache; hair loss and graying hair; gastrointestinal complaints; uterine disorders; microbial infections; as well as cancer [42, 43, 82]. Some of these claims may be attributable to the presence in the plant of various bioactive constituents including coumestans, thiophene derivatives, terthiophenes, flavonoids, as well as triterpenoids and their glycosides such as eclalbasaponins [82, 83].

Converging lines of evidence suggest that *E. prostrata* preparations and some of their constituents may elicit anticancer activity through multiple mechanisms including direct cytotoxicity, angiosuppression, and chemoprevention. The former possibility is supported by the growth inhibitory effects of crude extracts of the plant in a variety of drug-sensitive and drug-resistant cell lines [84–87] while causing apoptosis in some cases [87, 88]. Also, an orally administered methanolic leaf extract exerted encouraging anticancer activity against Ehrlich ascites carcinoma in Swiss albino mice [89], and a hydroalcoholic extract reversed multidrug resistance in an animal model of liver cancer induced by diethylnitrosamine and 2-acetylaminofluorene [86]. Furthermore, terthiophenes, thiophenes, saponins, triterpenoids, coumestans, and flavonoids isolated from the aerial parts exhibited cytotoxicity against cultured SKOV3 human ovarian cancer cells [90]; an eclalbasaponin I-containing fraction from the aerial parts and the saponin dasyscyphin-C isolated from the leaves inhibited the *in vitro* proliferation of SMMC-7721 human hepatocarcinoma and HeLa human cervical carcinoma cells, respectively [85, 91]; and eclalbasaponin II induced cytotoxicity as well as apoptotic and autophagic cell death in human ovarian cancer cell lines [92].

 That *E. prostrata* may also exhibit angiosuppressive activities can be derived from the inhibitory effect of the juice from the whole plant on invasion, migration, and adhesion of a variety of cancer cell types and endothelial cells in the chick chorioallantoic membrane assay [93]. And indications for chemopreventive actions of this plant were provided by the growth inhibitory effect of a coumastan-containing methanolic whole-plant extract in an experimental skin cancer in mice [94]. This presumably occurred by restoring endogenous antioxidant defense mechanisms, enhancing immunosurveillance, silencing cell cycle progression signals, and inducing stable expression of p53 [94].

#### **4.4 Fabaceae—***Abrus precatorius* **L., 1753**

The crab's eye or rosary pea *A. precatorius* (**Figure 5**) is a slender, woody, climbing plant that grows twisting around trees, shrubs, and hedges and probably originates from India. However, due to its severely invasive capacity, this plant is now commonly encountered in many tropical and subtropical parts of the world. Its deep roots are very difficult to remove, and its aggressive growth, hard-shelled seeds, and ability to sucker make it very difficult to eradicate and to prevent reinfestation. The brightly red colored seeds are used to make necklaces and other ornaments as well as percussion instruments in various cultures. However, they are very toxic because of their high content of the toxalbumin abrin, and ingestion of a single well-chewed seed can be fatal [95].

 The sweet-tasting leaves of the plant are used in West Tropical Africa to sweeten foods [96]. These parts of the plant along with the seeds (after denaturing abrin at high temperatures [97]) are also used in various traditional medicinal systems for treating or preventing tetanus, inflammation, snake bites, rabies, and leukoderma; as aphrodisiacs; as oral contraceptives and abortifacients; and for treating cancer [42, 98].

**Figure 5.**  *The crab's eye Abrus precatorius L., 1753 (Fabaceae) (from: https://goo.gl/images/8VobSd).* 

 Pharmacological studies with preparations from *A. precatorius* seeds and leaves revealed that many of their biological activities may be attributable to abrin [98]. This compound consists of a dimer with a B subunit that facilitates its entry into cells by binding to plasma membrane-associated transport proteins, after which the A subunit inactivates the 26S subunit of ribosomes, preventing protein synthesis [99]. One molecule of abrin is able to inactivate up to 1500 ribosomes per second [95], indicating its powerful inhibitory effect on protein synthesis. On the other hand, this mechanistic feature of abrin presents the opportunity of inhibiting the proliferation of cancerous cells which characteristically have a higher metabolic turnover when compared to normal cells.

Indeed, protein-rich extracts or peptide fractions from *A. precatorius* seeds and ethanol, ethyl acetate, and water extracts from the leaves potently inhibited the proliferation of several tumor cell lines [100–104] without affecting the growth of normal murine peritoneal macrophages [102]. The cytotoxic effects were accompanied by upregulation of particularly p21 and p53 levels [104] and clear signs of apoptosis occurring through the mitochondrial pathway [101]. The seed preparations also inhibited the growth of several tumor types implanted into laboratory rodents [105–108]. And direct injection of abrin into a murine Meth-A sarcoma growing in syngeneic BALB/c mice led to regression of the tumor [109]. The anticancer effects might be related to the antioxidant activities of phenolics and flavonoids in the extracts [102, 104].

 Importantly, administration of Meth-A tumor cells which had been treated *in vitro* with abrin, induced strong antitumor immunity of the mice [109]. This suggests that the antitumor effects of abrin were also produced by boosting the immune system. Support for this presumption came from the immunopotentiating and immunostimulatory properties of abrin [107, 110] and the behavior of *Abrus*  agglutinin as a B cell and T cell stimulator [111].

#### **4.5 Fabaceae—***Tephrosia sinapou* **(Bucholz) A.Chev.**

The Surinam poison *T. sinapou*, also known as *T. toxicaria* (Swartz) Pers. (**Figure 6**), is native to parts of Central America, the Caribbean, and tropical South America. The plant is mainly known for its high content of the isoflavonoids rotenone and tephrosin in its black roots and seeds, which are used as a fish poison by the Amazon Indigenous peoples [112, 113]. Particularly rotenone is also highly toxic to insects and pests [112, 113]. For this reason, Guyana hinterland peoples use the root sap or the leaf juice externally against head lice [112]. These preparations are also used to ward off evil spirits and for treating eczema, snakebites, syphilis,

*Anticancer Activity of Uncommon Medicinal Plants from the Republic of Suriname: Traditional… DOI: http://dx.doi.org/10.5772/intechopen.82280* 

**Figure 6.**  *The Suriname poison Tephrosia sinapou (Bucholz) A.Chev. (Fabaceae) (from: https://goo.gl/images/q6BZZN).* 

and gonorrhea, as well as skin ulcers associated with AIDS and cancer [42, 43, 114]. These health benefits have particularly been ascribed to the rotenoids and other flavonoids in roots, leaves, and aerial parts of the plant [115–117].

 Indications for anticancer activity of *Tephrosia* preparations were provided by the cytotoxic effects of extracts from parts of *T. calophylla* Bedd., *T. persica* Boiss., *T. purpurea* (L.) Pers., *T. villosa* (L.) Pers., and *T. vogelii* Hook F. against human carcinoma cell lines and brine shrimp cultures [118–124]. In some cases, the cytotoxic effects were accompanied by signs of apoptotic cell death [118]. Comparable anticancer effects were produced by benzil and coumestan derivatives from a *T. calophylla* root extract [125]; flavonoids from parts of *T. calophylla*, *T. pulcherrima*  (Baker) Gamble, and *T. pumila* (Lam.) Pers. [126]; phenol- and flavonoid-rich methanolic extracts from the leaves of *T. purpurea* and the aerial parts of *T. apollinea*  (Delile) DC. [124, 127]; and a prenylated flavone from the aerial parts of *T. apollinea*  [128]. Notably, the high flavonoid content of the aerial parts of *T. apollinea* has also been associated with potent anti-angiogenic activity in an *ex vivo* rat aortic ring assay [127].

 There are also indications for cancer chemopreventive activity of *Tephrosia*  preparations. Thus, flavonoids from an ethyl acetate-soluble extract of *T. sinapou*  stem selected for potential cancer chemopreventive properties in an *in vitro* assay for quinone reductase induction, inhibited the formation of preneoplastic lesions induced by DMBA in a mouse mammary organ culture [129]. Furthermore, *T. purpurea* extracts substantially reduced the formation of skin lesions in Swiss albino mice treated with the potent tumor promoter phorbol 12-myristate 13-acetate (PMA) following treatment with DMBA [130]. The extract also inhibited the development of hepatocellular carcinoma in Wistar rats treated with the carcinogenic and mutagenic compound N-nitrosodiethylamine [131].

#### **4.6 Loranthaceae—***Phthirusa stelis* **(L.) Kuijt**

The bird vine *P. stelis* (**Figure 7**) is, like many of its relatives in the plant family Loranthaceae (commonly known as mistletoes), a small flowering plant that grows

**Figure 7.**  *The bird vine Phthirusa stelis (L.) Kuijt (Loranthaceae) (from: https://goo.gl/images/J9D1zG).* 

 hemiparasitically on the branches of trees and shrubs. It is encountered in various Southern and Middle American countries between Costa Rica and Bolivia where it often constitutes a serious pest on cultivated trees of economic importance such as rubber, orange, cocoa, and bread fruit trees [132]. *P. stelis* is mostly spread by bird droppings, hence the abovementioned Surinamese vernacular name of "*pikin fowru doti*" meaning small birds' excrement.

None of the parts of the plant have edible uses. However, the viscous layer of its fruits has been suggested to represent a potential source of natural rubber [133]. *P. stelis*  preparations are traditionally used to treat oral candidiasis in children; leukorrhea; problems of the female reproductive system; tonsillitis; and skin problems such as scabies [42, 43, 134]. The plant is also used as a chemopreventive substance and by cancer patients for whom no other options are available, presumably because of its hemiparasitic, cancer-like lifestyle, which would signal its usefulness for these purposes [43].

 Indications for anticancer activity of *P. stelis* are scant, being limited to the cytotoxic effects of small polypeptides of 3–5 kDa isolated from dried dichloromethane or ethanol whole-plant extracts in cultured U-937 GTB human histiocytic lymphoma cells [135]. This finding is in line with the identification of (larger) cytotoxic peptides in the Loranthaceae species *Helicanthus elastica* (Desr.) Dans. [136] and *Ligaria cuneifoli*a (Ruiz & Pav.) van Tiegh. [137]. Other phytochemicals in Loranthaceae species with *in vitro* anticancer activity are alkynic fatty acids in *Scurrula atropurpurea* (BL.) Dans. [138]; lectins in *Viscum album coloratum* Kom. [139]; the triterpene moronic acid in *Phoradendron reichenbachianum* (Seem.) Oliv. [140]; glycosides in *Macrosolen globosus* (Roxb.) Tiegh. [141], *Loranthus tanakae*  Franch. & Sav. (Loranthaceae) [142], and *Viscum coloratum* (Kom.) Nakai [143]; and flavonoids in *L. cuneifolia* [144].

Crude extracts from stem or leaves of *Scurrula oortiana* (Korth.) Danser [145], leaves of *Dendrophthoe pentandra* (L.) Miq. [146], and stem *of Elytranthe parasitica* (L.) Danser [147] also exerted cytotoxic effects. In addition, the alkynic fatty acids from *S. atropurpurea* potently inhibited *in vitro* tumor cell invasion [148], and extracts from the stem or leaves of *S. oortiana* increased tumor cell sensitivity to TNF-α-mediated lysis [145].

*Anticancer Activity of Uncommon Medicinal Plants from the Republic of Suriname: Traditional… DOI: http://dx.doi.org/10.5772/intechopen.82280* 

### **4.7 Rubiaceae—***Uncaria guianensis* **(Aubl.) J.F. Gmel.**

 The cat's claw *U. guianensis* (**Figure 8**) is indigenous to the Amazonian parts of Paraguay, Brazil, Bolivia, Peru, Ecuador, Colombia, Venezuela, and the Guyanas. Preparations from its stembark and leaves have a long history of traditional medicinal use and are particularly employed for treating osteoarthritis and rheumatoid arthritis [42, 43, 149]. Pharmacological studies with extracts from *U. guianensis* and with those from other closely related species, mainly *U. tomentosum* (Willd. ex Schult.) DC—indeed showed anti-inflammatory activities [150]. These effects have primarily been attributed to pentacyclic oxindole alkaloids [149–152]. Clinical studies with an *U. guianensis* stembark extract or a highly purified pentacyclic oxindole alkaloids fraction from *U. tomentosum* reported some benefits in patients with osteoarthritis of the knee [153–155]. However, the overall clinical data are insufficient to draw a firm conclusion about the anti-inflammatory efficacy of *Uncaria*  preparations [156].

No studies have been carried out on the anticancer activity of *U. guianensis*. However, studies with the oxindole alkaloids from *U. tomentosa* stembark showed notable anticancer activity against human cancer cell lines [157–160] and a mouse model [159] which was in some cases accompanied by apoptosis [157]. In addition, *Uncaria* preparations may possess immunomodulatory and chemopreventive properties besides direct cytotoxic activity. The former assumption is supported by the involvement of anti-inflammatory processes rather than cytotoxic events in the antitumor activity of a hydroethanolic *U. guianensis* stembark extract in 4 T1 mammary tumor-bearing BALB/c mice [161]. The latter supposition stems from the changes in expression patterns of critical proto-oncogenes and tumor suppressor genes in DMBA-treated CBA/Ca mice following administration of Claw of Dragon tea (CoD™ tea), a mixture of the stembarks from *U. guianensis*, *U. tomentosa*, and the trumpet-tree *Tabebuia avellanedae* Lorentz ex Griseb. (Bignoniaceae) [162].

A clinical trial with a dried extract of *U. tomentosa* stembark reported improved overall quality of life, social functioning, and fatigue in patients with advanced solid tumors, but there were no improvements in biochemical and inflammatory markers or tumor responses [163]. Another trial found a decrease in the occurrence of neutropenia caused by the 5-fluorouracil-doxorubicin-cyclophosphamide combination in patients with breast cancer [164]. However, a third study found no effect of oral tablets containing a dried ethanolic *U. tomentosa* stembark on the most prevalent adverse events caused by the 5-fluorouracil-oxaliplatin regimen in colorectal cancer patients [165].

**Figure 8.**  *The cat's claw Uncaria guianensis (Aubl.) J.F. Gmel. (Rubiaceae) (from: https://goo.gl/images/7ezTTN).* 

## **4.8 Simaroubaceae—***Quassia amara* **L.**

The bitterwood *Q. amara* (**Figure 9**) is native to South and Central America but is now also cultivated in various other tropical and subtropical regions throughout the world. In Suriname, the plant has been named "kwasibita" (Kwasi's bitter) after the freedman Kwasi or Quassi (1692–1787) who was the first to broadly apply the remarkable medicinal properties of the hardwood for treating malaria fevers [28]. The plant contains triterpene quassinoids, secondary metabolites that are among the bitterest in nature [166]. These compounds are almost exclusively encountered in members of the Simaroubaceae and are a taxonomic marker of this plant family [166]. They constitute basic ingredients of Angostura bitters, concentrated alcoholic preparations produced by the House of Angostura in Trinidad and Tobago, which are key ingredients of cocktails such as gin-based drinks.

The quassinoids quassin, neoquassin, bruceantin, and simalikalactones D and E have been associated with a host of pharmacological activities including antimalarial, insecticidal, anti-inflammatory, antimicrobial, and antianorectic activities [166–168]. Other *Q. amara* phytochemicals with a broad pharmacological spectrum are canthin-6-one alkaloids, which displayed antiviral, antiparasitic, antibacterial, anti-inflammatory, and cytotoxic activities [166, 168, 169]. Notably, a 4%-*Quassia*  cream containing both groups of phytochemicals has been found safe and effective in the management of rosacea [170].

 There is ample evidence that *Q. amara* preparations and some of its constituents also possess anticancer activity. For instance, crude stem or leaf extracts, quassimarin- and/or similikalactone-enriched fractions, partially purified quassinoid-containing fractions, as well as quassimarin, similikalactones, and canthin alkaloids displayed substantial cytotoxicity against human carcinoma cell lines [171–174] as well as P-388 lymphocytic leukemia inoculated into laboratory mice [171]. Importantly, the quassinoids did not affect the viability of nontumorogenic African green monkey Vero kidney cells [173] and produced anticancer effects at lower concentrations than those required for antimalarial effects [172, 173]. Comparable results were found with quassinoids and/or canthin alkaloids from other members of the Simaroubaceae family [175–178]. Markedly, the quassinoids and canthin alkaloids also prevented the activation of Epstein-Barr virus early antigen by PMA [175] and inhibited the activity of CYP1A1, a cytochrome P450 isoform with presumed carcinogen-activating properties [179]. These observations suggest that these compounds may also possess chemopreventive properties.

Based on this large body of preclinical data, several *Q. amara* constituents have undergone clinical evaluation in patients with advanced solid and hematological

**Figure 9.**  *The bitterwood Quassia amara L. (Simaroubaceae) (from: https://goo.gl/images/d5ZqEd).* 

 malignancies. Unfortunately, the results from phase 1 and phase 2 studies with bruceantin—as well as Fructus bruceae oil obtained from the dried ripe fruits of *Brucea javanica* (L.) Merr.—were uniformly disappointing, showing no meaningful anticancer activity but substantial toxicity [180–182].
