Plants Used In Cancer Treatment

Part - III

Camptotheca acuminata – the happy tree

Camptotheca acuminata – the happy tree

Tree in the Nyssaceae (Liriodendron family)

Distribution Use in traditional medicine Late 1950s - NCI screening 1966 - a quinoline alkaloid camptothecin

(CPT) was isolated from bark (and wood)

Early clinical trials of CPT

Solubility problems with CPT 1985 interest renewed Late 1980s semi-synthetic derivatives Current status

– Two semi-synthetics approved: Topotecan (Hycamptin) and Irinotecan (Camptosar)

Other CPTs

Other CPTs undergoing clinical trials for various forms of cancer– 9-nitrocamptothecin– BAY-38-3441– Exatecan– 9-aminocamptothecin

CPTs also being investigated as anti-viral drugs, esp anti-HIV

Source of CPTs

Population decline of Camptotheca acuminata trees in China

Plantations in US Found in leaves Laboratory synthesis New source of CPTs - Camptotheca

lowreyana

Lapacho – Tabebuia impetiginosa

Lapacho

Tabebuia impetiginosa - tree in the family Bignoniaceae (catalpa family)

Distribution Traditional uses in South America Available as a dietary supplement Lapachol isolated in 1884 Beta-lapachone identified later

Lapachol and Beta-lapachone

Both are simple phenolic compounds

Lapachol is a napthaquinone

Beta-lapachone is a quinone

Both have anti-cancer properties but are both highly toxic

Evaluation

Early studies in South America NCI - effective but side effects too great Current investigations – Beta laphone

– Mode of action Derivative: 3-allyl-beta-lapachone Interest in anti-viral activity of beta-

lapachone Use of lapacho teas as dietary supplements

Fumagillin – an angiogenesis inhibitor from Aspergillus fumigatus

Aspergillus fumigatus

Morphology and characteristics of Aspergillus

Environmental sources Thermophilic fungus Human pathogen

Fumagillin

Antibiotic from Aspergillus fumigatus Discovered in 1953 – not widely used for

human infections – used for animals Recent interest as anti-malarial and other

protozoans Accidental discovery led to observation of

death of endothelial cell cultures

Fumagillin derivative

Animal studies showed fumagillin inhibited vascularization of tumors in mice but quite toxic

Semisynthetic derivatives of fumagillin developed

TNP-470 now in Phase I, II, and III clinical trials for various types of cancer

Inhibits vascularization of tumors by arresting endothelial cell cycle in late G1 stage

Iscador from Viscum album, European mistletoe

Iscador

Extract from Viscum album 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

Other sources

Many other plants, algae, fungi, and bacteria have anti-cancer properties

Some are used in chemotherapy Others in clinical trials Others still not developed Many others not investigated yet