Cancer is a type of diseases, in which uncontrollable cell growth of an organ or circulatory cells can be recognized anywhere in the body if any mutation take place in gene level. For controlling the cancer disease, the treatment therapy is considering various anticancer drugs which can suppress the uncontrollable growth of cells by interacting with cellular process. Such anticancer drugs are……
Mitomycin, Doxorubicin, Kanchanomycin, Streptonigrin, Phleomycin, Anthramycin, Plurmycin family drugs, Bleomycin, Dactinomycin, Plicamycin, Carboplatin, Cisplatin
Mitomycin: The antibiotic mitomycin is an anticancer alkylating agent, produced by Streptomyces caespitosus. Mitomycin can covalently bind the DNA molecule and creates cross-links between complementary strands and generates free oxygen radicals, thereby inhibiting the DNA synthesis. The drug has been used to treat upper gastro-intestinal cancers, breast cancers, anal cancers, and bladder tumour.
Doxorubicin: Doxorubicin (adriamycin and rubex) antibiotic binds between two strands of DNA (intercalating between DNA strands) and also relax the topoisomerase complexes by binding to topoisomerase II enzyme and it resulting into inhibition of DNA synthesis.
Kanchanomycin: The antibiotic kanchanomycin inhibits the DNA replication by creating complexion with polynucleotides (or DNA) in the presence of a stoichiometric amount of divalent cations Mg2+
Streptonigrin: Streptonigrin is an aminoquinoline antibacterial and antitumor antibiotic produced by Streptomyces flocculus. With the help of divalent cations Zn2+, Streptonigrin interacts with DNA (ssDNA or DS DNA)and then produces reactive oxygen species (free radicals), resulting into the cleavage of DNA.
Phleomycin: Phleomycin is a glycopeptide antibiotic produced from Streptomyces verticillus. This drug has the ability to bind the DNA and cause DNA fragmentation.
Anthramycin: Anthramycin (pyrrolobenzodiazepine) is a broad-spectrum antibiotic isolated from Streptomyces refuineus. This medicine has been used in cancer treatment because it inhibits RNA and DNA synthesis by binding irreversibly with DNA.
Plurmycin family drugs: The antibiotics of plurmycin family produced by fermentation of Streptomyces violaceus shows antitumor activity by inhibiting the DNA synthesis.
Bleomycin: The antibiotic bleomycin is a nonribosomal peptide produced by Streptomyces verticillus, which has the ability to break the DNA strand and cleavage of DNA by bleomycin mainly depends on oxygen and metal ions. Some studies suggest bleomycin inhibits DNA synthesis by preventing the incorporation of thymidine into DNA strands. However, the exact mechanism of DNA strand scission is unclear, but it has been stated that bleomycin chelates metal ions (primarily iron) and produces pseudoenzyme, that reacts with oxygen to produce hydroxide free radicals and superoxide that cleave DNA. The other studies suggested that bleomycin may bind DNA strand at specific sites and creates breaks by abstracting the hydrogen atom from the nucleotide bases.
Dactinomycin: Dactinomycin also called as actinomycin D, is a crystalline antibiotic composed of two cyclic peptide chains and phenoxazine chromophore produced by Streptomyces parvulusis. The drug can be used in a chemotherapy medication to treat various types of cancer. Dactinomycin intercalates (squeezing) between adjacent guanine-cytosine base pairs present in the double standard DNA and inhibits transcription (RNA synthesis) especially during chain elongation which is more sensitive than initiation and termination. Dactinomycin treatment completely inhibits the protein synthesis by inhibiting the RNA synthesis, it is resulting in cell death.
Plicamycin: Plicamycin (Mithracin, Mithramycinum or Mithramycin) is aureolic acid produced by Streptomyces plicatus. The drug can inhibit RNA and protein synthesis by interacting with DNA. It is used to treat various cancers such as bone cancer and testicular cancer. Plicamycin is also has been recommended to treat hypercalcemia, especially that due to malignancies.
Carboplatin: Carboplatin (Paraplatin) is an alkylating agent and used as anticancer ant chemotherapeutic drug. The drug has the ability to bind and damage the DNA and RNA, thereby inhibition of protein synthesis. The drug can treat various cancers includes ovarian cancer, head and neck cancer, brain cancer, lung cancer, and neuroblastoma.
Cisplatin: The alkylating agent Cisplatin is also an anti-cancer chemotherapy drug suggested to treat various types of cancers includes testicular cancer, cervical cancer, bladder cancer, ovarian cancer and breast cancer etc. It also has the ability to damage the DNA and RNA and induce the apoptosis by activating caspases.
Dactinomycin is an antitumor drug, that can inhibit the RNA synthesis by binding the DNA. However, for the binging of this drug the polypeptide strand should contain both guanine and cytosine nucleotides. The question is why cannot Dactinomycin drug bind RNA, which also contains both guanine and cytosine in its polypeptide strand?
- For binding, the drug requires deoxyribose nucleotides.
- Dactinomycin is only specific to DNA because DNA is longer than RNA
- Drug intercalates between adjacent guanine-cytosine base pairs present in the double strand DNA
- The drug can only bind DNA during transcription because it requires triplet (RNA and DNA bound region).