Anti-tumour activity of two 19-nor-clerodane diterpenes, trans-dehydrocrotonin and trans-crotonin, from Croton cajucara

The effects of two nor-diterpenes, trans-dehydrocrotonin (DCTN) and trans-crotonin (CTN) from Croton cajucara (Euphorbiaceae), on the survival of mice bearing Sarcoma 180 and Ehrlich carcinoma ascitic tumours, on the proliferation of cu[tu red Ehrlich cells and TNF alpha activity were determined. When the mice were treated with 80 and 120 mg/kg of DCTN or 38 mg/kg of 5-FU a significant anti-tumour activity was obtained (%T/C of 128-140). The cytotoxicity against Ehrlich carcinoma was 16 mu M for DCTN and CTN whereas the flavonoid quercetin was cytotoxic at 44 mu M in 48 h cell culture. No apoptosis was seen on in vitro electrophoresis of DNA extracted from the tumour cells treated with DCTN and CTN. A significant TNF alpha activity was detected in Ehrlich tumour-bearing mice treated with DCTN suggesting an enhanced immune function.