Plant sources of anti-cancer agents

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Extracts from Camptotheca (the "happy tree" or "cancer tree") were used to develop the chemotherapeutic drug Topotecan Camptotheca acuminata - United States Botanic Garden - DSC09523.JPG
Extracts from Camptotheca (the "happy tree" or "cancer tree") were used to develop the chemotherapeutic drug Topotecan

Plant sources of anti-cancer agents are plants, the derivatives of which have been shown to be usable for the treatment or prevention of cancer in humans. [1] [2]

Contents

Background

In the 1950s, scientists began systematically examining natural organisms as a source of useful anti-cancer substances. [1] It has recently been argued that "the use of natural products has been the single most successful strategy in the discovery of novel medicines". [3]

Plants need to defend themselves from attack by micro-organisms, in particular fungi, and they do this by producing anti-fungal chemicals that are toxic to fungi. Because fungal and human cells are similar at a biochemical level it is often the case that chemical compounds intended for plant defence have an inhibitory effect on human cells, including human cancer cells. [4] Those plant chemicals that are selectively more toxic to cancer cells than normal cells have been discovered in screening programs and developed as chemotherapy drugs [5]

Research and development process

Some plants that indicate potential as an anticancer agent in laboratory-based in vitro research  for example, Typhonium flagelliforme ,[ citation needed ] and Murraya koenigii [6] are currently being studied. There can be many years between promising laboratory work and the availability of an effective anti-cancer drug: Monroe Eliot Wall discovered anti-cancer properties in Camptotheca in 1958, but it was not until 1996  after further research and rounds of clinical trials   that topotecan, a synthetic derivative of a chemical in the plant, was approved for use by the US Food and Drug Administration. [7]

Plants

Camptotheca acuminata

The cancer treatment drug topotecan is a synthetic chemical compound similar in chemical structure to camptothecin which is found in extracts of Camptotheca (happy tree). [7]

Catharanthus roseus

Vinca alkaloids were originally manufactured by extracting them from Catharanthus (Madagascar Periwinkle). [1]

Podophyllum spp.

Two chemotherapy drugs, etoposide and teniposide, are synthetic chemical compounds similar in chemical structure to the toxin podophyllotoxin which is found in Podophyllum peltatum (May Apple). [1]

Taxus brevifolia

Chemicals extracted from clippings of Taxus brevifolia (Pacific yew) have been used as the basis for two chemotherapy drugs, docetaxel and paclitaxel. [8]

Euphorbia peplus

Contains ingenol mebutate (Picato) which is used to treat skin cancer [9]

Maytenus ovatus

Trastuzumab emtansine (Kadcyla) is an antibody conjugated to a synthetic derivative of the cytotoxic principle of the Ethiopian plant Maytenus ovatus. It used to treat breast cancer. [10]

Mappia foetida

Some of the research has been showed that it has an effective anticancer property against breast cancer

See also

Related Research Articles

<span class="mw-page-title-main">Chemotherapy</span> Treatment of cancer using drugs that inhibit cell division or kill cells

Chemotherapy is a type of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent or it may aim to prolong life or to reduce symptoms. Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.

<span class="mw-page-title-main">Paclitaxel</span> Medication used for cancer

Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer, and pancreatic cancer. It is administered by intravenous injection. There is also an albumin-bound formulation.

<i>Camptotheca</i> Genus of flowering plants in the family Nyssaceae

Camptotheca is a genus of medium-sized deciduous trees growing to 20 metres (66 ft) tall, native to southern China and Tibet. The genus is usually included in the tupelo family Nyssaceae, but sometimes included in the dogwood family Cornaceae.

<span class="mw-page-title-main">Vincristine</span> Chemical compound; chemotherapy medication

Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's disease, neuroblastoma, and small cell lung cancer among others. It is given intravenously.

<span class="mw-page-title-main">History of cancer chemotherapy</span>

The era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards and folic acid antagonist drugs. The targeted therapy revolution has arrived, but many of the principles and limitations of chemotherapy discovered by the early researchers still apply.

<span class="mw-page-title-main">Vinblastine</span> Chemical compound; chemotherapy medication

Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small cell lung cancer, bladder cancer, brain cancer, melanoma, and testicular cancer. It is given by injection into a vein.

<span class="mw-page-title-main">Podophyllotoxin</span>

Podophyllotoxin (PPT) is the active ingredient in Podofilox, which is a medical cream that is used to treat genital warts and molluscum contagiosum. It is not recommended in HPV infections without external warts. It can be applied either by a healthcare provider or the person themselves.

<span class="mw-page-title-main">Topotecan</span> Chemical compound

Topotecan, sold under the brand name Hycamtin among others, is a chemotherapeutic agent medication that is a topoisomerase inhibitor. It is a synthetic, water-soluble analog of the natural chemical compound camptothecin. It is used in the form of its hydrochloride salt to treat ovarian cancer, lung cancer and other cancer types.

<span class="mw-page-title-main">Lapatinib</span> Cancer medication

Lapatinib (INN), used in the form of lapatinib ditosylate (USAN) is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways. It is used in combination therapy for HER2-positive breast cancer. It is used for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 (ErbB2).

<i>Vinca</i> alkaloid

Vinca alkaloids are a set of anti-mitotic and anti-microtubule alkaloid agents originally derived from the periwinkle plant Catharanthus roseus and other vinca plants. They block beta-tubulin polymerization in a dividing cell.

Topoisomerase inhibitors are chemical compounds that block the action of topoisomerases, which are broken into two broad subtypes: type I topoisomerases (TopI) and type II topoisomerases (TopII). Topoisomerase plays important roles in cellular reproduction and DNA organization, as they mediate the cleavage of single and double stranded DNA to relax supercoils, untangle catenanes, and condense chromosomes in eukaryotic cells. Topoisomerase inhibitors influence these essential cellular processes. Some topoisomerase inhibitors prevent topoisomerases from performing DNA strand breaks while others, deemed topoisomerase poisons, associate with topoisomerase-DNA complexes and prevent the re-ligation step of the topoisomerase mechanism. These topoisomerase-DNA-inhibitor complexes are cytotoxic agents, as the un-repaired single- and double stranded DNA breaks they cause can lead to apoptosis and cell death. Because of this ability to induce apoptosis, topoisomerase inhibitors have gained interest as therapeutics against infectious and cancerous cells.

<span class="mw-page-title-main">Mitotic inhibitor</span> Cell division inhibitor

A mitotic inhibitor is a drug that inhibits mitosis, or cell division. These drugs disrupt microtubules, which are structures that pull the chromosomes apart when a cell divides. Mitotic inhibitors are used in cancer treatment, because cancer cells are able to grow and eventually spread through the body (metastasize) through continuous mitotic division. Thus, cancer cells are more sensitive to inhibition of mitosis than normal cells. Mitotic inhibitors are also used in cytogenetics, where they stop cell division at a stage where chromosomes can be easily examined.

<span class="mw-page-title-main">Camptothecin</span> Chemical compound

Camptothecin (CPT) is a topoisomerase inhibitor. It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. It was isolated from the bark and stem of Camptotheca acuminata, a tree native to China used in traditional Chinese medicine. It has been used clinically more recently in China for the treatment of gastrointestinal tumors. CPT showed anticancer activity in preliminary clinical trials, especially against breast, ovarian, colon, lung, and stomach cancers. However, it has low solubility and adverse effects have been reported when used therapeutically, so synthetic and medicinal chemists have developed numerous syntheses of camptothecin and various derivatives to increase the benefits of the chemical, with good results. Four CPT analogues have been approved and are used in cancer chemotherapy today, topotecan, irinotecan, belotecan, and trastuzumab deruxtecan. Camptothecin has also been found in other plants including Chonemorpha fragrans.

CRLX101 is a experimental approach to cancer chemotherapy that is under investigation in human trials. It is an example of a nanomedicine.

<span class="mw-page-title-main">Maitansine</span> Chemical compound

Maitansine (INN), or maytansine (USAN), is a cytotoxic agent. It inhibits the assembly of microtubules by binding to tubulin at the rhizoxin binding site.

<span class="mw-page-title-main">Antibody-drug conjugate</span> Class of biopharmaceutical drugs

Antibody-drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. As of 2019, some 56 pharmaceutical companies were developing ADCs.

<span class="mw-page-title-main">Trastuzumab emtansine</span> Pharmaceutical drug

Trastuzumab emtansine, sold under the brand name Kadcyla, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the cytotoxic agent DM1. Trastuzumab alone stops growth of cancer cells by binding to the HER2 receptor, whereas trastuzumab emtansine undergoes receptor-mediated internalization into cells, is catabolized in lysosomes where DM1-containing catabolites are released and subsequently bind tubulin to cause mitotic arrest and cell death. Trastuzumab binding to HER2 prevents homodimerization or heterodimerization (HER2/HER3) of the receptor, ultimately inhibiting the activation of MAPK and PI3K/AKT cellular signalling pathways. Because the monoclonal antibody targets HER2, and HER2 is only over-expressed in cancer cells, the conjugate delivers the cytotoxic agent DM1 specifically to tumor cells. The conjugate is abbreviated T-DM1.

Tubulin inhibitors are chemotherapy drugs that interfere directly with the tubulin system, which is in contrast to those chemotherapy drugs acting on DNA. Microtubules play an important role in eukaryotic cells. Alpha- and beta-tubulin, the main components of microtubules, have gained considerable interest because of their function and biophysical properties and has become the subject of intense study. The addition of tubulin ligands can affect microtubule stability and function, including mitosis, cell motion and intracellular organelle transport. Tubulin binding molecules have generated significant interest after the introduction of the taxanes into clinical oncology and the general use of the vinca alkaloids. These compounds inhibit cell mitosis by binding to the protein tubulin in the mitotic spindle and preventing polymerization or depolymerization into the microtubules. This mode of action is also shared with another natural agent called colchicine.

<span class="mw-page-title-main">Ingenol mebutate</span>

Ingenol mebutate, sold under the brand name Picato, is a substance that is found in the sap of the plant Euphorbia peplus, commonly known as milkweed, and is an inducer of cell death. A gel formulation of the drug has been approved by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for the topical treatment of actinic keratosis. Two different strengths of the gel have been approved for use on either the face and scalp (0.015%) or the trunk and extremities (0.05%), respectively. In 2020 the drug was withdrawn from the market in the EU.

This is a historical timeline of the development and progress of cancer treatments, which includes time of discovery, progress, and approval of the treatments.

References

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  2. Shoeb, Mohammad (2008). "Anticancer agents from medicinal plants". Bangladesh Journal of Pharmacology. 1 (2). doi: 10.3329/bjp.v1i2.486 .
  3. Tulp, Martin; Bohlin, Lars (2002). "Functional versus chemical diversity: Is biodiversity important for drug discovery?". Trends in Pharmacological Sciences. 23 (5): 225–31. doi:10.1016/S0165-6147(02)02007-2. PMID   12008000.
  4. Cardenas, ME; Cruz, MC; Del Poeta, M; Chung, N; Perfect, JR; Heitman, J (1999). "Antifungal activities of antineoplastic agents: Saccharomyces cerevisiae as a model system to study drug action". Clin. Microbiol. Rev. 12 (4): 583–611. doi:10.1128/CMR.12.4.583. PMC   88926 . PMID   10515904.
  5. "Discovery of Camptothecin and Taxol - National Historic Chemical Landmark". Archived from the original on 2015-06-20. Retrieved 2015-06-20.
  6. Syam, Suvitha; Abdul, Ahmad Bustamam; Sukari, Mohd. Aspollah; Mohan, Syam; Abdelwahab, Siddig Ibrahim; Wah, Tang Sook (2011). "The Growth Suppressing Effects of Girinimbine on Hepg2 Involve Induction of Apoptosis and Cell Cycle Arrest". Molecules. 16 (8): 7155–70. doi: 10.3390/molecules16087155 . PMC   6264672 . PMID   21862957.
  7. 1 2 "Topotecan (NSC 609699)". National Cancer Institute. Archived from the original on May 27, 2010. Retrieved August 27, 2013.
  8. "Yew clippings to make chemotherapy". Cancer Research UK. Archived from the original on September 8, 2022. Retrieved August 27, 2013.
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