How Do Chemotherapy Drugs Work?
04 January 2020
Today, cancer remains the largest cause of mortality in the world, claiming over six million lives each year. Chemotherapy is considered the cornerstone of treatment for many types of cancers. There are many types of agents used in chemotherapy. These drugs can be divided into several groups based on how they work and their chemical structure. Below are some common ones.
Alkylating Agents
Alkylating agents work by damaging the DNA (the genetic material in each cell) to keep the cell from reproducing. These drugs are used to treat many different cancers, including leukaemia, lymphoma, Hodgkin disease, as well as cancers of the lung, breast, and ovary. Examples include mechlorethamine, lomustine and busulfan.
Side effects: Predominant toxicities are to the bone marrow and gastrointestinal tract. It can also lead to acute leukaemia in rare cases.
Antimetabolites
Antimetabolites interfere with DNA and RNA growth, damaging cells when their chromosomes are being copies. They are commonly used to treat leukaemias, cancers of the breast, ovary, and intestinal tract. Examples include 5-fluorouracil, 6-mercaptopurine and capecitabine.
Anthracyclines
Anthracyclines are anti-tumour antibiotics that interfere with enzymes involved in DNA replication. They are widely used for a variety of cancers. Examples include daunorubicin, epirubicin and idarubicin.
Side effects: Permanent heart damage in high doses.
Mitotic inhibitors
Mitotic inhibitors are often plant-alkaloids and other compounds derived from natural products. They work by stopping mitosis in the M phase of the cell cycle. They are used to treat breast cancer, lung cancer, myelomas, lymphomas, and leukaemias. Examples include paclitaxel and docetaxel.
Side effects: Nerve damage at high doses. Since many chemotherapeutic drugs exhibit dose-limiting toxicities, there is an increased interest in alternative treatments that can reduce the toxicity of chemotherapy by lowering the drug concentration, while maintaining potency against cancer cells.
A US study in 2008 demonstrated that arabinoxylan from rice bran sensitises human breast cancer cells (BCC) to daunorubicin (DNR). Arabinoxylan from rice bran is a natural product obtained by reacting rice bran hemicellulose with multiple carbohydrate-hydrolysing enzymes from Shitake mushrooms. Data from the study suggested that food supplement Arabinoxylan from rice bran in conjunction with chemotherapy may be useful for the treatment of breast cancer.
Meanwhile, a 2014 study further evaluated the ability of Arabinoxylan from rice bran to sensitise cells to another chemotherapy agent, paclitaxel. The study showed that Arabinoxylan from rice bran increased the susceptibility of both metastatic and non-metastatic cancer cells to paclitaxel by over 100-fold. Mechanistically, Arabinoxylan from rice bran works synergistically with paclitaxel by causing DNA damage, enhancing apoptosis, and inhibiting cell proliferation. The study concluded that Arabinoxylan from rice bran is an effective chemosensitiser and may represent a novel adjuvant for the treatment of metastatic breast cancer.
References:
- American Cancer Society “Chemotherapy Drugs: How They Work” (www.cancer.org)
- Gollapudi S, Ghoneum M. MGN-3/Biobran, Modified Arabinoxylan from Rice Bran, Sensitizes Human Breast Cancer Cells to Chemotherapeutic Agent, Daunorubicin. Cancer Detect Prev. 2008;32(1):1-6, doi: 10.1016/j.cdp.2008.02.006. Epub 2008 Apr 11.
- Mamdooh Ghoneum, Nariman K. Badr El-Din, Doaa A. Ali And Mai Alaa El-Dein. Modified Arabinoxylan from Rice Bran, MGN-3/Biobran, Sensitizes Metastatic Breast Cancer Cells to Paclitaxel In Vitro. Anticancer Research 34: 81-88 (2014).
Tags: cancer,chemotherapy
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