Selective tumor cell growth inhibition by lignans and a seco-triterpenoid from Combretum mellifluum

Abstract

Two new tetrahydrofuran lignans 1-2, along with 2,3-seco-lup-20(29)-en-2,3-dioic acid(3), (-)-larreatricin (4), and 15 additional compounds were isolated from Combretum mellifluum (Combretaceae). Their structures were determined by 1D and 2D NMR spectroscopic data and HRESIMS. Another 15 compounds were identified after HPLC-DAD-MS/MS analysis. Tested against HT-29 (colon) neoplastic cells, lignan 1 showed marked cytotoxicity (GI50 = 3.9 µM) and high selectivity (SI > 227), compared with non-neoplastic NIH/3T3 cells, while 2 proved less cytotoxic, despite exhibiting SI > 75. Seco-triterpene 3 was strongly cytotoxic to 786-0 (kidney) and HT-29 cells (GI50 = 0.5 and 2.9 µM, respectively), proving roughly 107 and 18 times more selective for these cell lines, respectively, than for NIH/3T3 cells. After 48 h of incubation, 1-3 exhibited potent cytostatic activity against HT-29 cells at all concentrations tested, while 3 had a cytocidal effect on 786-0 cells at 25 µg.mL -1 .

Traditional Uses and Anticancer Potential of the Combretum Genus: A Literature Review

“…Combretastatin A4 phosphate undergoes clinical trials as an anticancer agent for the treatment of solid cancers [69,70]. (34) 2,3-seco-lup-20(29)-en-2,3-dioic acid 786-0 Kidney carcinoma 0.5 μM [81] HT-29 Colon adenocarcinoma 2.9 μM…”