**1. Introduction**

Cancer is one of the most severe health problems in both developing and developed countries, worldwide. Among the most common (lung, stomach, colorectal, liver, breast) types of cancers, lung cancer has continued to be the most common cancer diagnosed in men and breast cancer is the most common cancer diagnosed in women. An estimated 12.7 million people were diagnosed with cancer across the world in 2008, and 7.6 million people died from the cancer during the same year [1]. Lung cancer, breast cancer, colorectal cancer and stomach cancer accounted for two-fifths of the total cases of cancers diagnosed worldwide [1]. More than 70% of all cancer deaths occurred in low- and middle-income countries. Deaths due to cancer are projected to continuously increase and it has been estimated that there will be 11.5 million deaths in the year 2030 [1] and 27 million new cancer cases and 17.5 million cancer deaths are projected to occur in the world by 2050 [2]. According to Canadian cancer statistics, issued by the Canadian Cancer Society, it is estimated that 186,400 new cases of cancer (excluding 81,300 non-melanoma skin cancers) and 75,700 deaths from cancer will occur in Canada in 2012 [1]. The lowest number of incidences and mortality rate is recorded in British Columbia. Both incidence and mortality rates are higher in Atlantic Canada and Quebec [3].

More than 30% of cancers are caused by modifiable behavioral and environmental risk factors, including tobacco and alcohol use, dietary factors, insufficient regular consumption of fruit and vegetable, overweight and obesity, physical inactivity, chronic infections from *Helicobacter pylori*, hepatitis B virus (HBV), hepatitis C virus (HCV) and some types of human papilloma virus (HPV), environmental and occupational risks including exposure to ionizing and nonionizing radiation [4].

© 2013 Fernando and Rupasinghe; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Conventional treatment of cancer includes interventions such as psychosocial support, surgery, radiotherapy and chemotherapy [4]. Currently, the most commonly use cancer chemotherapy includes mainly alkylating agents, antimetabolites, antitumor antibiotics, platinum analogs and natural anticancer agents. However, due to the increasing rate of mortality associated with cancer and adverse or toxic side effects of cancer chemotherapy and radiation therapy, discovery of new anticancer agents derived from nature, especially plants, is currently under investigation. Screening of medicinal plants as a source of anticancer agents was started in the 1950s, with the discovery and development of vinca alkaloids, vinblastine and vincristine and the isolation of the cytotoxic podophyllotoxins [5] (Figure 01). The cool temperate climate of North America supports the growth of an enormous number of plant species which are important sources of unique phytochemicals having anticancer properties (Table 01). In this chapter, selected medicinal plants grown in the cool climate of North America (mainly Canada and USA) are discussed. The major bioactive phytochemicals and their mechanisms of action are also reviewed.

 (a) Vinblastine – [dimethyl (2β,3β,4β,5α,12β,19α)- 15-[(5S,9S)- 5-ethyl- 5-hydroxy- 9-(methoxycarbonyl)- 1,4,5,6,7,8,9,10-octahydro- 2H- 3,7-methanoazacycloundecino[5,4-b]indol- 9-yl] - 3-hydroxy- 16-methoxy- 1-methyl-6,7-didehydroaspidospermidine- 3,4-dicarboxylate] (b) Vincristin – [(3aR,3a1R,4R,5S,5aR,10bR)-methyl 4-acetoxy-3aethyl-9-((5S,7S,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-2,4,5,6,7,8,9,10-octahydro-1H-3,7-

methano[1]azacycloundecino[5,4-b]indol-9-yl)-6-formyl-5-hydroxy-8-methoxy-3a,3a1,4,5,5a,6,11,12-octahydro-1Hindolizino[8,1-cd]carbazole-5-carboxylate] (c) Podophyllotoxin – [(10*R*,11*R*,15*R*,16*R*)-16-hydroxy-10-(3,4,5 trimethoxyphenyl)-4,6,13-trioxatetracyclohexadeca-1,3(7),8-trien-12-one]

4

**Figure 1.** Some selected currently used phytochemical-based anticancer agents

Anticancer Properties of Phytochemicals Present in Medicinal Plants of North America http://dx.doi.org/10.5772/55859 161


Conventional treatment of cancer includes interventions such as psychosocial support, surgery, radiotherapy and chemotherapy [4]. Currently, the most commonly use cancer chemotherapy includes mainly alkylating agents, antimetabolites, antitumor antibiotics, platinum analogs and natural anticancer agents. However, due to the increasing rate of mortality associated with cancer and adverse or toxic side effects of cancer chemotherapy and radiation therapy, discovery of new anticancer agents derived from nature, especially plants, is currently under investigation. Screening of medicinal plants as a source of anticancer agents was started in the 1950s, with the discovery and development of vinca alkaloids, vinblastine and vincristine and the isolation of the cytotoxic podophyllotoxins [5] (Figure 01). The cool temperate climate of North America supports the growth of an enormous number of plant species which are important sources of unique phytochemicals having anticancer properties (Table 01). In this chapter, selected medicinal plants grown in the cool climate of North America (mainly Canada and USA) are discussed. The major bioactive phytochemicals and their

160 Using Old Solutions to New Problems - Natural Drug Discovery in the 21st Century

 **(a) Vinblastine (b) Vincristine (c) Podophyllotoxins**  *Metabolite Natural source Mode of action Ref* 

> Apocenacea Inhibition of microtubule assembly

Apocenacea Inhibition of microtubule assembly

Berberidaceae Inhibition of microtubule assembly

6, 7

6, 7

8, 9

*Botanical name Family* 

 (a) Vinblastine – [dimethyl (2β,3β,4β,5α,12β,19α)- 15-[(5S,9S)- 5-ethyl- 5-hydroxy- 9-(methoxycarbonyl)- 1,4,5,6,7,8,9,10-octahydro- 2H- 3,7-methanoazacycloundecino[5,4-b]indol- 9-yl] - 3-hydroxy- 16-methoxy- 1-methyl-6,7-didehydroaspidospermidine- 3,4-dicarboxylate] (b) Vincristin – [(3aR,3a1R,4R,5S,5aR,10bR)-methyl 4-acetoxy-3a-

methano[1]azacycloundecino[5,4-b]indol-9-yl)-6-formyl-5-hydroxy-8-methoxy-3a,3a1,4,5,5a,6,11,12-octahydro-1Hindolizino[8,1-cd]carbazole-5-carboxylate] (c) Podophyllotoxin – [(10*R*,11*R*,15*R*,16*R*)-16-hydroxy-10-(3,4,5-

(Madagascar periwinkle)

(Madagascar periwinkle)

(Himalayan mayapple)

ethyl-9-((5S,7S,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-2,4,5,6,7,8,9,10-octahydro-1H-3,7-

4

mechanisms of action are also reviewed.

Vinblastine *Catharanthus roseus*

Vincristine *Catharanthus roseus*

Podophyllotoxins *Podophyllum hexandrum*

trimethoxyphenyl)-4,6,13-trioxatetracyclohexadeca-1,3(7),8-trien-12-one]

**Figure 1.** Some selected currently used phytochemical-based anticancer agents



**Table 1.** Medicinal plants with potential anticancer properties grown in North America
