Cytotoxic Resin Glycosides from Ipomoea aquatica and Their Effects on Intracellular Ca²⁺ Concentrations

Abstract

Eleven new resin glycosides, aquaterins I-XI (1-11), were isolated from the whole plants of Ipomoea aquatica. The structures of 1-11 were elucidated by a combination of spectroscopic and chemical methods. They were found to be partially acylated tetra- or pentasaccharides derived from simonic acid B and operculinic acids A and C. The site of the aglycone macrolactonization was placed at C-2 or C-3 of the second saccharide moiety, while the two acylating residues could be located at C-2 (or C-3) of the second rhamnose unit and at C-4 (or C-3) on the third rhamnose moiety. All compounds were evaluated for cytotoxicity against a small panel of human cancer cell lines. Compound 4 exhibited the most potent activity against HepG2 cells with an IC50 value of 2.4 μM. Cell cycle analysis revealed 4 to inhibit the proliferation of HepG2 cells via G0/G1 arrest and apoptosis induction. In addition, compounds 1-4, 7, 9, and 10 were found to elevate Ca(2+) in HepG2 cells, which might be involved in the regulation of the cytotoxic activities observed.

Down‐regulation of aquaporin 5‐mediated epithelial‐mesenchymal transition and anti‐metastatic effect by natural product Cairicoside E in colorectal cancer

“…CE, a resin glycoside isolated from Ipomoea cairica , inhibited multiple tumor cells proliferation in our earlier study . Resin glycosides were reported to exert laxative properties, and had a potent anti‐tumor effect . AQP5, as an important regulator of body water metabolism, is critical to osmoregulation, may be involved in the laxative properties of resin glycosides.…”

Edible freshwater macrophytes: a source of anticancer and antioxidative natural products—a mini-review

“…Sequential fractionation of active extracts with organic solvents, for example, petroleum ether, acetone, dichloromethane, ethyl acetate, butanol and methanol (Khlifi et al 2013;Tagne et al 2014) has also been reported. The cytotoxicity assay most widely used for estimating the anticancer potential of EFM is the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (Babykutty et al 2008;Fan et al 2014;Liu et al 2014;Park et al 2005), but other assays such as the sulphorhodamine B (SRB), neutral red, and lactate dehydrogenase (LDH) leakage assays have also been used (Aboul-Enein et al 2014;Prasad et al 2005;Rose et al 2005). The MTT assay gives an indication of whole cell cytotoxicity.…”

“…Flow cytometric analysis, apoptosis-specific assays (i.e., acridine orange/ethidium bromide staining; annexin/propidium iodide staining), mitochondrial membrane potential visualization assay, DNA fragmentation assay, gene expression analysis, reverse transcription-polymerase chain reaction (RT-PCR) assay, and Western blot analysis have been used to study the induction of apoptosis by extracts and compounds isolated from EFM (Aboul-Enein et al 2014;Babykutty et al 2008;Chen et al 2014;Dwarka 2012;Engel et al 2014;Hussin et al 2014;Zhang et al 2013b). Instrumental analyses such as reversed-phase high performance liquid chromatography (RP-HPLC), gas chromatography (GC), mass spectrometry (MS), infrared (IR) and nuclear magnetic resonance (1D and 2D NMR) (Boyd et al 2006;Fan et al 2014;Ooh et al 2014) were used to detect, characterize, and identify potential anticancer compounds from EFM.…”

“…The isolation of 11 resin glycosides (aquaterins I-XI) from I. aquatica was recently reported (Fan et al 2014). Based on MTT assays, most of the resin glycosides exhibited low cytotoxicity against the human cancer cell lines tested.…”

“…Aquaterin IV was the most cytotoxic resin glycoside against the HepG2 cells, which had an IC 50 value (2.4 lM) lower than that of cis-platinum (IC 50 6.4 lM). Cell cycle analysis found that aquaterin IV inhibited HepG2 cell proliferation by G 0 /G 1 arrest and apoptosis induction (Fan et al 2014). 7-O-b-D-glucopyranosyl-dihydroquercetin-3-O-a-D-glucopyranoside (DHQG) isolated from I. aquatica crude methanolic extract was investigated for cytotoxicity by using MTT and SRB assays.…”