**2.1 Geography, population, demographics, and economy**

 The Republic of Suriname is situated in the north-eastern part of South America adjacent to the Atlantic Ocean and has a land area of roughly 165,000 km2 (**Figure 1**). The population of about 570,000 is among the ethnically most varied in the world, comprising Amerindians, the original inhabitants; Maroons, the immediate descendants of enslaved Africans shipped from western Africa between the seventeenth and the nineteenth century; Creoles, a generic term referring to anyone having one or more African ancestors; the descendants from indentured laborers attracted from China, India, and Java (Indonesia) between the second half of the nineteenth century and the first half of the twentieth century; as well as immigrants from various European, South American, and Caribbean countries [16].

#### **Figure 1.**

*Location of Suriname with respect to its neighboring countries French Guiana, Brazil, and Guyana, as well as its position in South America (insert) (from: https://goo.gl/images/F77jgS).* 

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

 Suriname can be characterized as a demographically transitioning country with declining mortality and infertility rates as well as a growing and aging population. These changes are for an important attributable to considerable progress in health care, nutrition, sanitation, and drinking water quality; the eradication of various infectious diseases; as well as improvements in average living and working conditions, education, and income [17, 18]. The result was a decline of the death rate from 24 per 1000 in 1923 to 6 per 1000 in 2011 and the attainment of an average life expectancy of 70 years in 2011 [17].

The country's most important economic means of support are crude oil drilling as well as gold and bauxite mining [19]. These activities, together with agriculture, fisheries, forestry, and ecotourism, have substantially contributed to Suriname's gross domestic income (GDI) in 2014 of USD 5.21 billion and the average *per capita income* in that year of USD 9325 [19]. This positions Suriname on the World Bank's list of upper-middle income economies [20].

#### **2.2 Health care**

Suriname spends about 5.7% of its GDI—which amounted to USD 589 *per capita*  in 2014—to health care [21]. This sum covers the health costs for the economically weakest individuals; insurance for government employees and employees of government-related companies; import and distribution of essential pharmaceuticals; vaccination programs; maternal and child health care; programs to fight parasitic and microbial diseases; dental care for schoolchildren; services for dermatological diseases, sexually transmitted diseases, and HIV/AIDS; as well as a Kidney Dialyses Center and a Blood Bank [21].

 Primary health care in Suriname is offered by the government-subsidized Regional Health Services and Medical Mission, as well as approximately 250 general practitioners. The Regional Health Services run 43 community health centers staffed with physicians and nurses, covers the entire coastal area, and offers basic laboratory testing as well as curative and preventive services including cervical cancer screening and dental, prenatal, and obstetric care. The Medical Mission is a nongovernmental organization that provides health services to people living in Suriname's hinterland. The clinics are staffed with community health workers who are supervised by general practitioners who travel back and forth on a regular basis.

 Secondary care is provided by two private and two government-supported hospitals in Paramaribo and one public hospital in the western district of Nickerie. Medical emergencies can turn around-the-clock to the First-aid Stations of the Academic Hospital Paramaribo and the Saint Vincentius Hospital Suriname. The Academic Hospital Paramaribo also functions as training facility for both general practitioners and medical specialists. All hospitals have modern clinical laboratory facilities as well as radiology services at their disposal. There are, in addition, four private clinical laboratories and three private radiology clinics. Diagnostic imaging including computed tomography and magnetic resonance imaging is possible at two private clinics and the Academic Hospital Paramaribo. This hospital also provides tertiary care at a Thorax Center, a Neurology High-Care Unit, a Neonatal Care Unit, and a Radiotherapy Center.

#### **3. Cancer in Suriname**

#### **3.1 Epidemiology**

As in many other low- and middle-income countries, there is no populationbased cancer registry in Suriname. The occurrence of cancer in the country is

estimated from data on the histopathologically confirmed cases at the Pathologic Anatomical Laboratory of the Academic Hospital Paramaribo that functions as the country's cancer-based registry. This institution reported for 2014 a crude incidence rate of 133 per 100,000 population with the most common cancers being breast, colorectal, prostate, and cervical cancer [22]. An earlier publication [23] mentioned an average of 70 per 100,000 population for the period 1980–2000, suggesting an almost twofold increase in the occurrence of cancer in Suriname since the turn of the century.

 Cancer mortality in Suriname has been registered since 1958. In the period between 1962 and 1970, the average death rate due to cancer was 60 per 100,000 per year [24]. This figure had risen to approximately 72 in 2011, ranking cancer as the second most common cause of mortality in the country, after cardiovascular diseases [25]. The top five causes of cancer mortality in that year were prostate, lung, rectum-sigmoid, female breast, and cervical cancer [25]. Most of the fatalities in females were attributable to breast and cervical cancer, while prostate cancer was the leading cause of cancer death in males [25].

### **3.2 Allopathic forms of cancer treatment in Suriname**

Suriname has no national guidelines for the screening, diagnosis, and treatment of cancer, and structured screening programs for breast, cervical, and colon cancer are nonexistent. For these reasons, a comprehensive national cancer control plan has been developed [22] that will be executed in the short term by the Ministry of Health.

 Still, primary prevention programs such as mandatory vaccination against the hepatitis B virus (since 2011) and the availability of a HPV vaccine for young girls (implemented in 2013) may help reduce the cancer burden in the country. This may also be achieved by early detection services such as screening for cervical and breast cancer, even though these facilities are in general utilized on an *ad hoc* basis. Cervical cancer screening occurs upon referral and is done at the Lobi Foundation, a nongovernmental organization for reproductive preventive services, using cytology (Pap smear) or visual inspection with acetic acid. Unfortunately, the coverage of this program is below 20% and thus has probably little impact on cervical cancer mortality [26]. Mammography, breast ultrasound, and fine needle aspiration for the assessment of breast lesions are since 2009 possible at two private clinics and two hospitals. Stereotactic (mammogram-guided) breast biopsy has been available since 2018 at the Academic Hospital Paramaribo. Cancer-specific evaluations such as testing for hormone receptors and tumor markers, are carried out at the Pathologic Anatomical Laboratory of this hospital.

Surgery, radiation therapy, and chemotherapy as standard therapeutic modalities for cancer are all available in Suriname. Surgical treatment is offered by all four hospitals in Paramaribo. Radiation therapy has been available since 2012 and is performed by two radiation oncologists. Chemotherapy is delivered by two oncologists and two gynecologic oncologists. If diagnostic or therapeutic services are not available in Suriname, patients can be transferred to health centers abroad provided that they have a good prognosis and are younger than 70 years. More than half of the selected patients are treated in Bogotá, Columbia. All costs are covered by the Surinamese Ministry of Health through the State Health Foundation [21].

#### **3.3 Traditional forms of cancer treatment in Suriname**

All ethnic groups in Suriname have preserved their own specific identity including their particular forms of traditional medicine, probably as a means of *Anticancer Activity of Uncommon Medicinal Plants from the Republic of Suriname: Traditional… DOI: http://dx.doi.org/10.5772/intechopen.82280* 

strengthening the ethnic identity after their relocation to their new homeland [27, 28]. Not surprisingly, the use of various traditional medicinal systems—involving, among others, Indigenous, African, and Chinese traditional medicine, Indian Ayurveda, as well as Indonesian Jawa—is deeply rooted in Suriname [27, 28]. Furthermore, Suriname's large biodiversity provides ample and readily available raw material that can be processed into ethnopharmacological plant-based preparations [29]. As a result, many diseases including cancer are often treated with such medications instead of, or in conjunction with, allopathic forms of treatment [30] despite the availability of affordable and accessible modern health care throughout the entire country.

 This holds true for, for instance, patients who are motivated by aversion of "chemical" drugs with attendant adverse or side effects and those whose philosophy about life is not compatible with the use of allopathic medicine or who have reservations about the viewpoints of allopathic medicine [31]. Others prefer traditional treatments because these modalities would improve conventional therapies and represent gentler means of managing their disease when compared to allopathic medicines [32]. Still other patients, particularly those with advanced disease or cancer that, from a medical standpoint, can no longer be treated, resort to traditional medicines as an ultimate means to improve their situation [33]. And cultural beliefs, traditional values, and certain perceptions of health and disease may entice some people to choose for a familiar traditional therapy rather than a "western" therapy [34, 35].

## **4. Plants for treating cancer in Suriname**

Hereunder, nine plants that are used in Suriname for treating cancer have in detail been assessed for their presumed activity against this disease. The plants have been selected after consulting a number of comprehensive publications describing various aspects of medicinal plants in the country [36–43]. Several of these plants such as the graviola *Annona muricata* L. (Annonaceae), *Aloe vera* (L.) Burm.f. (Asphodelaceae), the bitter melon *Momordica charantia* L. (Cucurbitaceae), the neem tree *Azadirachta indica* A.Juss., 1830 (Meliaceae), *Moringa oleifera* Lam. (Moringaceae), several subspecies and varieties of the black nightshade *Solanum nigrum* L. (Solanaceae), as well as the noni *Morinda citrifolia* L. (Rubiaceae) have elaborately been dealt with in the literature. This led us to decide to leave these plants out of the current chapter and address a number of less well-known plants, which *prima facie* may not qualify for evaluation for their anticancer potential (**Table 1**).

#### **4.1 Annonaceae—***Annona squamosa* **L.**

The sugar apple *A. squamosa* (**Figure 2**) is probably native to the tropical parts of South America and the Caribbean but is now widely cultivated for its flavorful fruit in many other tropical and subtropical regions throughout the world. Unripe fruits as well as seeds and leaves contain toxic alkaloids with effective vermicidal and insecticidal properties [44]. For these reasons, the seed oil is commonly used to treat head lice [44]. *A. squamosa* preparations are also used against gastrointestinal ailments, urinary tract infections, irregular menstrual flow, and cancer [42, 43, 45]. The therapeutic efficacy of some of these applications may be attributed to acetogenins, terpenes and terpenoids, as well as alkaloids [45, 46].

The seed oil as well as the essential oils from the pericarp, the leaves, and the stembark of *A. squamosa* displayed anticancer activity against a broad range of human cancer cell lines [47–62] as well as H22 hepatoma implanted into laboratory


#### **Table 1.**

*Plants with anticancer activity addressed in this chapter, parts preferentially used, presumed constituents with anticancer and chemoprotective activity, and references supporting these activities.* 

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

mice [51, 60–63]. The anticancer effects have particularly been attributed to annonaceous acetogenins in the seed oil [47–53, 59] as well as annonaceous acetogenins, terpenes, and terpenoids, and alkaloids in pericarp, leaves, and stembark [56–58, 60–62]. Interestingly, the acetogenin squamoxinone-D displayed selective cytotoxicity against the (drug-resistant) SMMC 7721/T cell line [59], and annonaceous acetogens were highly active in H22 hepatoma-bearing laboratory mice [64].

 The antitumor activities have in some cases been associated with cycle arrest effects and apoptotic events [54, 60–62] as indicated by the increased caspase-3 activity, the downregulation of antiapoptotic genes, and the fragmentation of the nuclear DNA [54, 60]. The mechanism underlying these events presumably involves the generation of oxidative stress [54]. This supposition is based on the enhanced generation of intracellular reactive oxygen species and the decreased levels of intracellular glutathione species noted in cultured human cells undergoing apoptosis following exposure to *A. squamosa* seed oil [54, 60].

Notably, leaf and stembark extracts protected Swiss albino mice and Syrian golden hamsters from the mutagenic effects of the alkylating agent cyclophosphamide [65] or the potent laboratory carcinogen 7, 12 dimethylbenz(a) anthracene (DMBA) [66], respectively. Furthermore, aqueous and ethanolic stembark extracts decreased lipid peroxidation and potentiated antioxidant activities in an animal model of oral carcinogenesis [67]. These observations suggest that *A. squamosa* also possesses chemopreventive properties.

#### **4.2 Asteraceae—***Cyanthillium cinereum* **(L.) H.Rob.**

The little ironweed *C. cinereum*, also known as *Vernonia cinerea* (L.) Less. (**Figure 3**), is native to the tropical parts of Africa and Asia but has become naturalized in various other tropical regions including those in South America and the Caribbean. The plant is traditionally used for treating genitourinary disorders, gastrointestinal complaints, and respiratory ailments; to stimulate perspiration in malaria patients; against childhood conditions including bed-wetting; and to fight cancer [42, 43, 68]. *C. cinereum* seeds yield vernonia oil that contains vernolic acid [69], a natural epoxy fatty acid that may serve as a renewable starting material for manufacturing adhesives, paints, dyes, coatings, composites, and plastics [70].

 Pharmacological and phytochemical studies have shown a wide range of bioactive compounds such as (a) sesquiterpene lactone(s), which may lend credit to the traditional uses [68]. Two clinical trials found *C. cinereum* preparations efficacious in smoking cessation [71], while one study reported encouraging results with a

herbal *C. cinereum*-containing preparation in patients with type 2 diabetes mellitus [72]. However, the clinical evidence available at this moment is insufficiently sound to support these applications [73].

Support for anticancer activity of *C. cinereum* came from the potent cytotoxicity of an extract from the whole plant against various drug-sensitive and multidrugresistant human tumor cell lines [74–76]. The whole-plant extract caused the cells to apoptose and sensitized them to common cytotoxic drugs [76]. Furthermore, such an extract as well as the sesquiterpene lactone vernolide A stimulated the activity of cytotoxic T lymphocytes and natural killer cells and enhanced antibody-dependent cellular cytotoxicity and antibody-dependent complement-mediated cytotoxicity in tumor-bearing BALB/c mice by increasing the secretion of interleukin-2 and interferon-γ [77]. This suggests that (this) sesquiterpene lactone may play an important role in the anticancer activity of *C. cinereum* [68, 78].

 Other indications for anticancer activity of *C. cinereum* preparations were the inhibitory effects of a 70%-methanol whole-plant extract on the *in vitro* proliferation, invasion, migration, and matrix metalloproteinase activation of B16F-10 murine melanoma cells [79]. The extract also prevented the formation of lung metastases by the B16F-10 cells in C57BL/6 mice, lowered vascular-endothelial growth factor (VEGF) levels in the animals, and substantially increased their life span when compared to untreated controls [79]. Together, these observations raise the possibility that *C. cinereum* may exert its anticancer activity by boosting the immune system, suppressing angiogenesis, and inhibiting drug transport mechanisms in addition to direct cytotoxicity.
