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Anti-tumor antibiotics
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RNA polymerase inhibition p. 38
targets of p. 446
dactinomycin for p. 448
dactinomycin for p. 448
dactinomycin for p. 448
dactinomycin for p. 447
All right, we know that antibiotics kill microbes, but a certain class of antibiotics called antitumor antibiotics can kill cancer too. Antitumor antibiotics include products that are produced from Streptomyces bacteria like: bleomycin; anthracyclines like doxorubicin and daunorubicin; and dactinomycin, also called actinomycin D. These medications interfere with DNA replication and often damage the DNA itself, leading to cell death. Most of them are cell cycle non-specific. Now, the cell cycle refers to the events that somatic cells go through in order to divide into two identical daughter cells.
The cell cycle can be divided in two phases: interphase and mitosis. Interphase starts with the G1 phase during which the cell grows and performs its cell functions. At the end of G1, there’s a control point called the G1 checkpoint - where the cell checks to see if the DNA is damaged and it synthesized the right proteins in the correct amount. If there is any reason for the cell not to divide, the cell can either enter a non-dividing state, called the G0 phase, where the DNA repair mechanisms try to fix the problem, or the cell can self-destruct in a process called apoptosis.
Now, if the cell does get the go-ahead at the G1 checkpoint, it enters the S phase during which DNA is replicated. All right, so during DNA replication, we unzip the double helix with the enzyme DNA helicase, and this creates a replication fork, with the two prongs of the fork being the two strands that are separated from one another. Now, as DNA helicase does its thing, the segments of DNA ahead of it start to overwind, meaning, the double helix becomes more tightly wound. Overwinding of the DNA can slow down replication, so the enzyme DNA topoisomerase works ahead of DNA helicase to loosen up the tight DNA coils.
Next, RNA primase creates a matching RNA primer on one pron of the replication fork. This is the area where the next enzyme, DNA polymerase, can bind to the DNA to use it as a template and start adding nucleotides that’s complementary to the DNA onto the end of the primer. Eventually we get a completed complementary copy of the DNA. Next is the G2 phase, during which the cell grows again before entering mitosis. However, before it can do that, it must pass the final G2 checkpoint to make sure there is no DNA damage after replication. Now, during mitosis, the replicated DNA divides equally for the two daughter cells, and the cell cycle ends with cytokinesis, which is when the cell membrane actually divides to form the two new cells.
Antitumor antibiotics refer to a type of anticancer drug that interferes with cell growth by disabling DNA replication, thus leading to cellular death. There are different types of antitumor antibiotics. Common antitumor antibiotics are mitomycin, anthracyclines which include drugs like doxorubicin, actinomycin D, and bleomycin.
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