1. Plants Used In Cancer Treatment Part - III

2. Camptotheca acuminata – the happy tree

3. n Tree in the Nyssaceae (Liriodendron family) n Distribution n Use in traditional medicine n Late 1950s - NCI screening n 1966 - a quinoline alkaloid camptothecin (CPT) was isolated from bark (and wood)

5. Early clinical trials of CPT n Solubility problems with CPT n 1985 interest renewed n Late 1980s semi-synthetic derivatives n Current status – Two semi-synthetics approved: Topotecan (Hycamptin) and Irinotecan (Camptosar)

6. Other CPTs n Other CPTs undergoing clinical trials for various forms of cancer – 9-nitrocamptothecin – BAY-38-3441 – Exatecan – 9-aminocamptothecin n CPTs also being investigated as anti-viral drugs, esp anti-HIV

7. Source of CPTs n Population decline of Camptotheca acuminata trees in China n Plantations in US n Found in leaves n Laboratory synthesis n New source of CPTs - Camptotheca lowreyana

8. Lapacho – Tabebuia impetiginosa

9. Lapacho n Tabebuia impetiginosa - tree in the family Bignoniaceae (catalpa family) n Distribution n Traditional uses in South America n Available as a dietary supplement n Lapachol isolated in 1884 n Beta-lapachone identified later

10. Lapachol and Beta-lapachone n Both are simple phenolic compounds n Lapachol is a napthaquinone n Beta-lapachone is a quinone n Both have anti-cancer properties but are both highly toxic

11. Evaluation n Early studies in South America n NCI - effective but side effects too great n Current investigations – Beta laphone – Mode of action n Derivative: 3-allyl-beta-lapachone n Interest in anti-viral activity of beta- lapachone n Use of lapacho teas as dietary supplements

12. Fumagillin – an angiogenesis inhibitor from Aspergillus fumigatus

13. Aspergillus fumigatus n Morphology and characteristics of Aspergillus n Environmental sources n Thermophilic fungus n Human pathogen

14. Fumagillin n Antibiotic from Aspergillus fumigatus n Discovered in 1953 – not widely used for human infections – used for animals n Recent interest as anti-malarial and other protozoans n Accidental discovery led to observation of death of endothelial cell cultures

15. Fumagillin derivative n Animal studies showed fumagillin inhibited vascularization of tumors in mice but quite toxic n Semisynthetic derivatives of fumagillin developed n TNP-470 now in Phase I, II, and III clinical trials for various types of cancer n Inhibits vascularization of tumors by arresting endothelial cell cycle in late G1 stage

16. Iscador from Viscum album, European mistletoe

17. Iscador n Extract from Viscum album n Widely used as a complementary therapy to conventional chemotherapy drugs – Lectins appear to be active components – Stimulates parts of the immune system that can slow the growth of cancer cells – Improves quality of life for cancer patients

18. Other sources n Many other plants, algae, fungi, and bacteria have anti-cancer properties n Some are used in chemotherapy n Others in clinical trials n Others still not developed n Many others not investigated yet