Chromatin function inhibitors

There are two classes of drugs that inhibit chromatin activity which are derived from plants, and are used in cancer chemotherapy regimens. 

The first class are semisynthetic derivatives of epipodophyllotoxin which is extracted from the American mayapple plant (Podophyllum peltatum) and consists of etoposide and teniposide. These drugs are glycosides and are potent inhibitors of chromatin activity due to targetting topoisomerase II (DNA gyrase) and DNA-binding complex I. These interactions destabilize the tension of the DNA molecule and contribute to double strand breaks. Tumor cells have difficulty repairing such breaks since they rely on the topoisomerase enzyme more than normal cells. Etoposide has clinical usefulness in solid tumors (testicular, lung, neuroblastoma etc.) as well as hematologic malignancies (leukemias and lymphomas). Myelosuppression (which is the major dose-limiting toxicity) is a well-known side effect. Hypotension and infusion-site pain/reactions are also commonly reported. Anaphylactic reactions are possible but less encountered. Paradoxically, when used for solid tumor treatment, these drugs can produce secondary leukemias (even though they can also treat such leukemias).  

The second class is derived from camptothecin, from the bark of a tree (Camptotheca acuminata) and consists of irinotecan. This is a prodrug which is converted by liver and GI enzymes (carboxylesterases) to the active metabolite, SN-38 which is 1000x more potent than the parent compound. Irinotecan is a potent inhibitor of topoisomerase I which leads to single-strand breaks which, in a similar fashion to double strand breaks observed with the first class, cancer cells have difficulty repairing. Irinotecan is used for several GI cancers, such as colon and pancreatic cancers. Diarrhea is the key dose-limiting toxicity, but myelosuppression and secondary leukemias are also possible. As benign as diarrhea sounds it is clinically significant, and must be monitored and managed, since it can have an impact on quality of life and can be life-threatening if dehydration ensues or if it is associated with neutropenia.