**3. Plant-based compounds with anticancer features**

The chemistry and biology of plants to fight against malignant cells are wide and diverse. Various classes of metabolites have been reported to possess valuable anticancer properties. As a recall, taxol, one of the mostly used anticancer drug in chemotherapy, is a complex diterpene-based metabolite; vinblastine, used in the therapy of various cancer as well, is made up of terpenic indol-type alkaloids and artemisinin or parthenolide actually in active clinical trials for cancer drugs possess a sesquiterpenoid lactone backbone. Since 2010, more than 72 compounds have



#### *Plant-Derived Compounds against Microbial Infections and Cancers DOI: http://dx.doi.org/10.5772/intechopen.92596*




*Melanoma (MDA-MB-435, A2058 and SK-Mel-2); human non-small-cell lung (H522-T1), ovarian cancer (A2780), human epidermoid carcinoma (KB), human lung adenocarcinoma (LU-1), breast (MDA-MB-231), gastric (AGS), human myeloid leukemia (K562), human gastric (SGC-7901), human-lung-tumor (A549). Murine leukemia (P-388), human pancreatic (Pan C1 and SW1990), human cervical carcinoma (Hela), mouse leukemia (P388), human leukemia (HL-60 and ALL-SIL), mouth epidermal carcinoma cells (KB), breast cancer (MCF-7 and MDA-MB-231) lung cancer (A549), hepatocellular carcinoma (HepG2), human promyelocytic leukemia (HL60), human chronic myeloid leukemia (K562), Blymphocyte (Raji), colon carcinoma (LS174T), human neuroblastoma (IMR-32), skin carcinoma (SK-MEL-28), colon (HCT-8), liver (Bel-7402), stomach (BGC-823), ovarian (A2780), lung (A549). Myeloid leukemia (HL-60 and K562), lung (A549), hepatocellular carcinoma (HepG2), colon (HT-29), ovarien (A2780), melanoma (A2058), non-small-cell lung cancer (H522-T1), lymphoblastic leukemia cell line (CCRF-CEM), resistant T-cell leukemia cell line (CEM-ADR5000), the pancreatic, carcinoma cell line (MIA PaCa-2)–, and on peripheral blood mononuclear cells (PBMC) from healthy human subjects, HeLa (cervical carcinoma), Jurkat (T-cell leukemia), and U937 (monocytic leukemia) cell lines, human acute lymphoblastic leukemia (CEM), and normal human skin fibroblasts (BJ), human breast (MDA-MB-231), human gastric (HGC-27), human leukemia (CCRF-CEM).*

#### **Table 2.**

*Examples of significant secondary metabolites with antiproliferative properties.*

been reported with considerable antiproliferative activity against different cancer cell lines with IC50 ranging from 0.001–10 μM.

These compounds are distributed in homoisoflavonoids (**45**–**60**), isoprenylflavonoids (**61**–**63**, **68**–**70**), stilbenoids (**64**–**67**), xanthones (**71**–**72**), benzophenanthridines (**73**–**82**), *Amaryllidaceae*-type alkaloids (**83**–**86**), cardenolides (**87**–**90**) and sesquiterpenoid lactones (**91**–**117**). Their respective sensibility toward tumor cell lines are depicted in **Table 2** and their respective structures in **Figure 2**. As expected, sesquiterpenoid lactones were the most exploited metabolites. They are reputed for their ability to induce apoptosis in cancer cell lines with good selectivity. Homoisoflavonoids were the second most important group of compounds found to exhibit high cytotoxicity herein. The interest in this class of metabolites for anticancer solution is most likely related to their potency as inhibitor of angiogenesis both *in vitro* and *in vivo*, without showing any toxicity [80]. On the other hand, benzophenanthridines are reputed for their bioavailability because they contained more often ionic bond besides their bioactivity. Their mode of action in cancer therapy includes either the inhibition of mitosis via a reaction of the imine bond with the sulfhydryl nucleophile in protein and enzyme or the enzymatic activities of DNA Topoisomerase I and Topoisomerase II by implantation into DNA molecules to retard the fast proliferation of tumor cells [81].

#### **4. Natural products in active development for drug discovery**

Knowing the categories of compounds which has been screened and choose for clinical trials is quite important. It can help redefine our objectives and outlines in research. However, such information is not accessible easily. Almost all pharmaceutical makers keep this information for private uses. Nevertheless, available reports before 2010 on valuable compounds in development for cancer therapy for instance can continue to be used and analyze. There are privilege structures with

*Plant-Derived Compounds against Microbial Infections and Cancers DOI: http://dx.doi.org/10.5772/intechopen.92596*

**Figure 2.** *Bioactive compounds against cancer cell lines.*

#### *Plant-Derived Compounds against Microbial Infections and Cancers DOI: http://dx.doi.org/10.5772/intechopen.92596*

unique structurally subunits which confer to drugs distinctive therapeutic affinities to a biological system. These core molecules include β-lactam unit like in penicillin; cyclopentanoperhydrophenanthrene fragment like in testosterone; pyrone, coumarins, isoflavone, or chalcone moieties and alkaloids like quinoline, isoquinoline or indole units.

As an example, since the large-scale screening for anticancer agents launched in the USA in 1960, more than 3000 sesquiterpene lactones have been reported. Most of them are with cytotoxic properties. Sesquiterpene lactones are well-known for their ability to bind sulfhydryl-containing peptides, mainly in proteins, presented as important route in well- programed death of a cell [82–85]. This property and other have raised up interests in this class of compounds. Many members of this class are currently in clinical trials for drug development including parthenolide, artemisinin or thapsigargin among others.

Another most important class of phytocompounds in cancer therapy is phenolic compounds. Members of these classes of metabolites are reputed in caspase activation causing apoptosis in tumor cell lines. Research found that furanocoumarins for instance in grapefruit showed significant effects towards breast cancer, the second World leading cause of cancer-related death among Women [86]. In the same line, coumarine-type of compounds known as calanolides, isolated from *Calophyllum* species have been found to be active against lymphoblastic cells infected with HIV-1 [87]. They are currently in clinical trials Phase II to drug development. Likewise, all other phenolic compounds listed above can also undergo similar interactions with cancer cells. Anthraquinones, and quinones, in general form the basic core of many anticancer drugs known as anthracyclines. Resveratrol, a stilbene-like metabolite, is being continuously checked to explain issues encountered during laboratory trials against cancer in animal model. However, association of resveratrol with established anticancer drugs like clofarabine has been proved against mesothelioma cell lines [88].

### **5. Conclusion**

The World is facing an unprecedented drastic climate change that impacts negatively not only on human beings but also plants. New metabolism routes have surely emerged leading to compounds with unprecedented structures for some and with relevant bioactivities for others. However, nothing is being done to take advantages of this wealth for our health care always relying on "modern drugs." We should start exploring ways to use natural products with anticancer effects along with standard chemotherapy treatments to increase potency while reducing side effects of actual drugs. This strategy is currently being used in the USA. We highlighted relevant bio-sensibility of some compounds and they should now be investigated as main constituents to a standardization process of their respective plant extracts. The present survey can also help researchers in developing countries working on plants, to re-focus their research works.

#### **Acknowledgements**

The authors would like to acknowledge the Yaounde-Bielefeld Graduate School of Natural Products with Antiparasite and Antibacterial Activities (YaBiNaPA, www.yabinapa.de) for the research stay granted at the University of Bielefeld in Germany under the project No. 57316173.
