In vitro Activity of Hederacolchisid A1 Compared with Other Saponins from Hedera colchica Against Proliferation of Human Carcinoma and Melanoma Cells

Abstract

Hederacolchisid A1, a new oleanolic acid monodesmoside, isolated from Hedera colchica K. Koch, an ivy species endemic in Georgia, was evaluated in vitro for antiproliferative activity on cancer cells versus normal cells in comparison to cisplatin. Investigations were made on six human cell lines (colon adenocarcinoma DLD-1, ovarian teratocarcinoma PA 1, lung carcinoma A 549, breast adenocarcinoma MCF7, prostatic adenocarcinoma PC 3 and malignant melanoma M4 Beu) versus normal human fibroblasts, by assaying both cellular metabolic activity (RTT test) and DNA content in living cells (test with Hoechst 33,342) after 48 h continuous contact. Results demonstrated the strong cytotoxicity of hederacolchisid A 1 on all cancer cells (IC50 from 4.5 to 12 microM). The antiproliferative effects on malignant melanoma M4 Beu (IC50 ca 4.5 microM) versus normal cells (IC50 ca 7.5 microM) suggests that, despite a lack of specificity for cancer cells, hederacolchisid A1 has potential anti-tumor applications. Comparison of the cytotoxicity of hederacolchisid A 1 with that of five other saponins from H. colchica, offers some new information about structure-activity relationships. It was observed that i) for a same sugar sequence, monodesmosides with oleanolic acid as aglycone exhibit higher cytotoxicity than those containing hederagenin, ii) the sugar sequence O-alpha-L-rhamnopyranosyl (1 --> 2)-alpha-L-arabinopyranoside at C3 induces strong cytotoxicity and might be identified as a basic sequence for anti-tumor activity of oleanolic acid monodesmosides. iii) a complementary glucopyranosyl moiety branched at C1 of arabinose increases the cytotoxicity against malignant melanoma M4 Beu, prostatic adenocarcinoma PC 3 and normal fibroblasts in a different manner for each type of monodesmoside. A slight increase whose amplitude was quite similar on cancers and normal cells, was observed with oleanolic acid monodesmoside. This increase was much higher with hederagenin monodesmoside and markedly elevated in normal cells than in cancer cells.

Effects of Hedera helix L. extracts on rat prostate cancer cell proliferation and motility

“…Previously, researchers have been focused on in vitro and in vivo studies using saponins and their derivatives obtained from various parts (including, leaves or fruits) of herbal sources, and certain Hedera species (18,(28)(29)(30). Triterpenoid saponins such as α-hederin, β-hederin, δ-hederin, hederacosides A-I, hederacolchisides (A, A 1 and B) and hederagenin are the primary phytochemical components in Hedera spp.…”

“…Triterpenoid saponins such as α-hederin, β-hederin, δ-hederin, hederacosides A-I, hederacolchisides (A, A 1 and B) and hederagenin are the primary phytochemical components in Hedera spp. (15,16,18). Saponin derivatives isolated from Hedera spp.…”

“…Saponin derivatives isolated from Hedera spp. (18,28) and other plants (29,30) produce antiproliferative, antitumor and cytotoxic effects (18,28), as well a range of other biological activities [including, antimicrobial (19), antifungal (20), anthelmintic (21) and antileishmanial (22)]. In the present study, crude extracts of H. helix leaves and fruits were used.…”

“…Barthomeuf et al (18) isolated certain saponin derivatives, including α-hederin, β-hederin, δ-hederin, hederacolchiside (A and A1) and hederagenin, from H. colchica fruits and used them for treating 6 human cancer cell lines (PC-3, DLD-1, PA1, A549, MCF7 and M4Beu) and a human fibroblast cell line. It was observed that hederacolchiside A 1 and β-hederin had the highest inhibitory activity on cancer cell lines (18). It was also observed that these two compounds were cytotoxic against fibroblast cells, but that the concentration producing this cytotoxicity was increased compared with the dose required for inhibiting the proliferation of cancer cell lines (18).…”

“…Saponin derivatives obtained from Hedera spp. have numerous biological activities, including antiproliferative, cytotoxic (17,18), antibacterial (19), antifungal (20), anthelmintic (21), antileishmanial (22), anti-elastase and anti-hyaluronidase (23) effects. de Medeiros et al (24) demonstrated that H. helix spp.…”