Antineoplastic plant origin

The main agents of this group are vinblastine, vincristine, vinorelbine, docetaxel, irinotecan, paclitaxel, teniposide, topotecan, etoposide, etc.
According to the classification of D.A. Kharkevich, herbal anticancer agents can be represented by the following groups:
1. Alkaloids of pink vinca – vinblastine, vincristine.
2. Yew tree alkaloids (taxanes) – paclitaxel, docetaxel.
3. Podophyllotoxins secreted from the thyroid podophyllum – etoposide, teniposide.
4. Alkaloids of colchicum magnificent – demecolcine (colhamin), colchicine.
Most alkaloids are phase-specific antineoplastic agents, i.e. effective in certain phases of the cell cycle.
Taxanes belong to a class of drugs that act on microtubules. Unlike vinca alkaloids, which inhibit the formation of the mitotic spindle, taxanes, by binding to free tubulin, increase the rate and degree of its polymerization, stimulate the assembly of microtubules, stabilize formed microtubules, and prevent tubulin depolymerization and microtubule disintegration. Taxanes disrupt cell function during mitosis (M-phase) and in interphase.
The formation of an excessive number of microtubules and their stabilization lead to inhibition of the dynamic reorganization of the microtubule network, which ultimately leads to a disruption in the formation of the mitotic spindle and inhibition of the cell cycle in G2 and M-phases. Changes in cell functioning in interphase, incl. violation of intracellular transport, transmission of transmembrane signals, etc. is also a consequence of a violation of the microtubular network.
Paclitaxel and docetaxel have a similar mechanism of action. However, differences in the chemical structure determine some nuances in the mechanism of action of these substances found in the experiment. For example, docetaxel has a more pronounced effect on the activation of tubulin polymerization and inhibition of its depolymerization (approximately two times). Under the action of paclitaxel on the cell, some changes in the structure of microtubules are characteristic, which were not detected under the action of docetaxel. Thus, experimental studies have shown that microtubules formed in the presence of paclitaxel contain only 12 protofilaments (instead of 13 in the norm) and have a diameter of 22 nM (in contrast to 24 in the norm).
In addition, paclitaxel induces an abnormal bundle of microtubules throughout the cell cycle and the formation of multiple stellate clumps (asters) during mitosis.
The mechanisms of action of various drugs that affect microtubules remain not fully understood, despite the large amount of accumulated information. It was found that the sites of binding with tubulin are different for natural vinca alkaloids, vinorelbine, colchicine, and taxanes. Thus, in experimental studies of paclitaxel, it was shown that it predominantly binds to the beta-subunit of tubulin, while its ability to bind to microtubules is higher than that of tubulin dimers.
Taxanes are effective for breast cancer, ovarian cancer, non-small cell lung cancer, head and neck tumors, etc.
Podophyllotoxins. Antineoplastic agents of plant origin include podophyllin (a mixture of natural substances secreted from rhizomes with roots of thyroid podophyllum). (Podophyllum peltatum L.) family of barberry (Berberidaceae). Podophyllin contains at least 40% podophyllotoxin, alpha and beta peltatins. The extract from the rhizomes of podophyllum has long been used in folk medicine as a laxative for chronic constipation, as an emetic and antihelminthic agent. Subsequently, its cytostatic activity was discovered, manifested by the blockade of mitosis at the metaphase stage (it resembles colchicine in action). Podophyllotoxin is used topically in the treatment of papillomas and other skin neoplasms.
In clinical practice, semi-synthetic derivatives of podophyllotoxin are widely used – epipodophyllotoxins (etoposide and teniposide), which are related to topoisomerase inhibitors by the mechanism of action.
Topoisomerases are enzymes that are directly involved in the process of DNA replication. These enzymes change the topological state of DNA: by making short-term breaks and reunions of DNA sections, they promote rapid unwinding and twisting of DNA during replication. At the same time, the integrity of the chains is preserved.
Topoisomerase inhibitors, binding to the topoisomerase-DNA complex, affect the spatial (topological) structure of the enzyme, reduce its activity and thereby disrupt the process of DNA replication, inhibit the cell cycle, delaying cell proliferation.
Topoisomerase inhibitors have a phase-specific cytotoxic effect (during periods S and G2 phase of the cell cycle).
Etoposide and teniposide are topoisomerase II inhibitors.
Camptothecins – semi-synthetic derivatives of camptothecin alkaloid isolated from bush stems Camptotheca acuminata,represented by irinotecan and topotecan. In accordance with the mechanism of action, they belong to the group of topoisomerase inhibitors. Unlike epipodophyllotoxins, camptothecins are topoisomerase I inhibitors. Irinotecan is currently the first-line drug for the treatment of colon cancer. Topotecan is widely used in the treatment of lung and ovarian cancer.
Below is a list of herbal anticancer agents:

  • Paclitaxel
  • Podophyllotoxin
  • Vinblastine
  • Vinorelbin
  • Etoposide
  • Vincristine
  • Topotecan
  • Teniposide
  • Cabazitaxel
  • Docetaxel
  • Vinflunine
  • Irinotecan
  • Trabektedin
  • Vindesine