Vinca Alkaloids

Four major vinca alkaloids are in clinical use for cancer: vinblastine, vinorelbine, vincristine, and vindesine.

These are sometimes called monoterpenoid indole alkaloids in the scientific literature. All vinca alkaloids are administered intravenously. They are eventually metabolized by the liver and excreted.

Inside the Malignant Cells

The vinca alkaloids are cytotoxics – they halt the division of cells and cause cell death. Specifically, they can be classified as microtubule target agents.  During cell division, vinca alkaloid molecules bind to the building blocks of a protein called tubulin, inhibiting its formation. The drugs work during the M-phase of cell reproduction. Tubulin protein normally works in cells to create “spindle fibers” (also called microtubules). These microtubules provide cells with both the structure and flexibility they need to divide and replicate. Without microtubules, cells cannot divide. The vinca alkaloid’s mechanism in a nutshell: by occupying tubulin’s building block structure, vinca alkaloids prevent cancer cells from successfully dividing.

In addition to interfering in multiplication of malignant cells, Vinblastine inhibits angiogenesis, or the process by which new blood vessels grow from pre-existing ones. Angiogenesis is an essential step in a tumor’s transition to malignancy. Vinblastine is most often applied to treat Hodgkin’s disease, non-Hodgkin’s lymphoma, breast cancer, and germ cell tumors. Side effects of vinblastine include: toxicity to white blood cells, nausea, vomiting, constipation, dyspnea, chest or tumor pain, wheezing, and fever. Vinblastine sometimes causes antidiuretic hormone secretion and angina.

Vinorelbine acts the same way as vinblastine. Vinorelbine stops or slows tumor growth in breast cancer and has antiproliferation effects on osteosarcoma (bone tumor cells). Furthermore, vinorelbine has been shown to decrease the stability of lipid bilayer membranes (like those of a cell’s). Vinorelbine’s side effects include: decreased resistance to infection, bruising or bleeding, anemia, constipation, diarrhea, nausea, numbness or tingling in the hands and feet, fatigue (also called peripheral neuropathy), and inflammation at the injection site. Less common side effects include hair loss and allergic reaction.

Vincristine’s inhibition of microtubule formation is powerful. This is because the tubulin protein is dynamic; its long chain of amino acids is always growing in some places and breaking in others. The less contiguous parts of a tubulin molecule have pieces only two amino acids long, called dimers. Vincristine has a high affinity for tubulin dimers, and the reaction between vincristine and the dimers is rapidly reversible. That means a vincristine molecule will attach to a dimer at one site, break off, and then reattach at another site. This keeps two sites per dimer “poisoned” and unable to reassemble into the protein. So vincristine’s ability to destabilize tubulin is especially effective.

Vincristine is FDA approved to treat acute leukemia, rhabdomyosarcoma, neuroblastoma, Wilm’s tumor, Hodgkin’s disease, and other lymphomas. Vincristine’s most common side effects are: peripheral neuropathy, suppression of bone marrow activity, constipation, nervous system toxicity, nausea, and vomiting.

Vindesine has a serum half-life of only 24 hours, but similar effects (intended and side) to that of vinblastine. Vindesine is administered at a dose of 3 milligrams per square meter of body surface. The drug is applied to treat melanoma, lung cancers, and (combined with other drugs) uterine cancers. Additional side effects from vindesine include: anemia, blood cell toxicity, fatigue, tingling or pricking sensations in the skin, and skin toxicity.

vinca alkaloid mechanism

Clinical Use

The vinca alkaloids are a subset of drugs derived from the Madagascar periwinkle plant. They were discovered in the 1950’s by Canadian scientists, Robert Noble and Charles Beer.

Information on the exact usage rates of Vinca alkaloid drugs is scant, but sales figures show decreases for all of the cytotoxics used to treat cancer in the past decade. In 2005, cytotoxics represented the majority of the top 20 cancer therapeutics, according to In the past decade, however, molecular targeted therapies have taken an increasing share of the market.

Nonetheless, vinca alkaloids remain among the fundamental cancer therapies.

They have also been used in treatment of hypertension and as disinfectants. The leaves of the periwinkle plant can be used to make a tea and it was once thought this tea would have a benefit for people with diabetes. Scientific investigation did not confirm this benefit exists.

Nature’s Binary

Interesting thing about the periwinkle – although these compounds are derived from the leaves, they do not exist in significant quantities inside the plant while the plant is alive. The plants do contain precursor alkaloids vindoline and catharanthine. The catharanthine is in the waxy coating of the leaves. When the leaves are broken – say by an animal looking for food – an opportunity is formed for mixing of the catharanthine and vindoline and for synthesis of the chemicals oncologists find useful in fighting cancer. It is not known why evolution resulted in segregation of the two precursors, but it might be because vinblastine, etc. have toxic effects on the periwinkle plant. In a somewhat analogous setup, the US Army stocks binary chemical weapons – weapons that don’t become poisonous until two constituents interact and produce a chemical reaction on the battlefield.

PDF list of Vinca Alkaloids


Brand/Trade Names: Alkaban-AQ, Velban

Formula: C46H58N4O9

Mechanism: Antimicrotubule

Class: Plant alkaloid

Administration: Intravenous

Notes: A mitotic inhibitor.  Approved by the FDA in 1961.  Used for treatment of breast cancer, choriocarcinoma, lymphoma, sarcoma,  and testicular cancer.


Brand/Trade Names: Navelbine

Formula: C45H54N4O8

Mechanism: Antimicrotubule

Class: Plant alkaloid

Administration: Intravenous

Notes:  Approved by the FDA in 1994.  Approved for treatment of non-small cell lung cancer.


Brand/Trade Names: Oncovin, Vincasar Pfs, Leurocristine

Formula: C46H56N4O10

Mechanism: Antimicrotubule

Class: Plant alkaloid

Administration: Intravenous

Notes:  Approved by the FDA in 1963.  Used for treatment of leukemia, neuroblastoma, lymphoma, rhabdomyosarcoma, and Wilms tumor.


Brand/Trade Names: Eldisine

Formula: C43H55N5O7

Mechanism: Antimicrotubule

Class: Plant alkaloid

Administration: Intravenous

Notes:  Approved by the FDA in 1994.  Used for melanoma, lymphoma, testicular, breast, non-small cell lung cancer, head and neck, and bladder cancers, sarcoma, and choriocarcinoma