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ago in Medicinal Chemistry by (390 points)
How does the drug doxorubicin work in treating cancer, and what specific cellular processes and pathways does it target?

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ago by (350 points)
Doxorubicin is an anthracycline antibiotic and a widely used chemotherapeutic drug for treating various types of cancer, including breast cancer, ovarian cancer, lung cancer, and leukemia. It works by targeting and disrupting several cellular processes and pathways essential for cancer cell growth and proliferation. The main mechanisms of action of doxorubicin include:1. DNA intercalation: Doxorubicin intercalates between the base pairs of the DNA double helix, causing DNA strands to unwind and separate. This process inhibits the activity of essential DNA processing enzymes, such as topoisomerase II, which is required for DNA replication, transcription, and repair. As a result, cancer cells cannot replicate their DNA and divide, leading to cell death.2. Topoisomerase II inhibition: Doxorubicin forms a stable complex with topoisomerase II and DNA, preventing the enzyme from resealing the DNA breaks it creates during the process of DNA replication and transcription. This leads to the accumulation of double-strand DNA breaks, which are highly toxic to cells and can trigger cell death through apoptosis.3. Generation of reactive oxygen species  ROS : Doxorubicin can undergo redox cycling in cells, leading to the production of reactive oxygen species, such as superoxide anions, hydrogen peroxide, and hydroxyl radicals. These ROS can cause oxidative damage to cellular components, including DNA, proteins, and lipids, ultimately leading to cell death.4. Induction of apoptosis: By causing DNA damage and oxidative stress, doxorubicin can activate cellular pathways that lead to programmed cell death, or apoptosis. This includes the activation of tumor suppressor proteins, such as p53, and the initiation of the intrinsic mitochondrial apoptotic pathway.5. Immunomodulatory effects: Doxorubicin has been shown to modulate the immune system by increasing the expression of certain immune-stimulatory molecules on cancer cells, making them more susceptible to immune-mediated destruction.In summary, doxorubicin targets multiple cellular processes and pathways, including DNA replication, transcription, and repair, topoisomerase II activity, oxidative stress, and apoptosis, to exert its anti-cancer effects.
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