Since the 1940s, humans have begun to use synthetic, small-molecule inhibitors to treat tumors. A series of drugs, such as alkylating agents, fluorouracil, methotrexate, cyclophosphamide, have been launched on the market. However, most of these molecules have large side effects. Since the 1950s, drug developers in many countries and regions, including the United States, began to focus on natural small molecules that have anti-cancer effects. For example, the National Cancer Institute (NCI) commissioned botanists in the United States Department of Agriculture (USDA) in 1960 to provide 1,000 plants each year for the National Cancer Chemotherapy Service Center (CCNSC) for the screening of anticancer drugs. Over the years of efforts, more natural products with anti-cancer effects have been found and successfully marketed, becoming star therapeutic drugs in the corresponding field. Let’s see what these natural compounds are.
1. Paclitaxel — the first tubulin inhibitor
Initially, researchers discovered white alkaloid toxic constituents from the branches and leaves of Taxus chinensis (Pilger) Rehd., but they didn’t know what the specific substances are. Then, American researcher Barclay specially extracted taxus samples and screened them for activity and found it has significant antitumor activity. In further extraction studies, researchers found the most active white crystalline monomer in the extract and named it paclitaxel.
Since then, paclitaxel has been found to have a tubulin inhibitory effect. It is also the first tubulin inhibitor to be discovered by humans. In 1984, the FDA approved clinical trials of paclitaxel and officially granted its marketing approval in 1992. At present, paclitaxel has become a recognized broad-spectrum antitumor drug in the world, and further drug development on paclitaxel has not ceased. In 2004, FDA approved the listing of a paclitaxel derivative, docetaxel.
2. Camptothecin
Camptothecin is isolated from Camptotheca Acuminata, a unique plant of the Davidia involucrata family in China, and has significant antitumor effects. Since the research found that camptothecin is different from general chemotherapeutics, the activity of topoisomerase I has attracted great interest from researchers. Starting from the 1960s, many drug developers have begun drug development of camptothecin and its derivatives. FDA approved the listing of camptothecin derivatives topotecan and irinotecan, which marks the expanded contribution of camptothecin to the antitumor combat.
3. Homoharringtonine: still effective in imatinib-resistant populations
Chinese folks have a long history of using Cephalotaxus Fortunei to treat cancer. Subsequent research has proved that the chemical constituents of the plants, including harringtonine, homoharringtonine, hetero harrington Ester base, deoxyharringtonine, and pseudodehydroharringtonine, have significant inhibitory effects on the growth of leukemia cells. In 2012, the FDA accelerated the approval of homoharringtonine for the treatment of leukemia. In particular, homoharringtonine is still effective in imatinib-resistant populations, which has attracted much attention and achieved success.
4. Ginsenoside Rg3: a new class of antitumor drugs
Ginsenoside Rg3 is a dammarane-type tetracyclic triterpenoid saponin, whose chemical structure was determined in 1983, and subsequently proved to have antitumor effects. It is a new class of anti-tumor drugs developed in China and has also obtained a number of international patents. Ginsenoside Rg3 is also one of the representative drugs of natural antitumor products.
5. Vinblastine and colchicine
Vinblastine and vinblastine are isolated from vinca flowers of the oleander family and have been shown to have significant antitumor effects. Eli Lilly and Company has invested a lot of energy in this field, and obtained clinical approval from FDA in 1963 through clinical trials. It is also a classic old medicine in the anti-cancer history. Furthermore, colchicine is also an old medicine targeted for the treatment of cancer, fibrosis and inflammation.
In addition to the drugs mentioned above, podophyllotoxin, pinnin, indorubin, berberine, agroglycine, anisin, and gossypol are also natural product molecules that have been marketed and play important roles in their respective fields. Moreover, in recent years, with the deepening of the understanding and emphasis on natural products in the drug research and development community, it has brought many new opportunities for the development of natural anti-tumor molecules, such as naphthol. It is certain that natural medicine will play a greater role in the antitumor field in the future.

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BOC Sciences