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 A₁ on all cancer cells (IC₅₀ from 4.5 to 12 μM). The antiproliferative effects on malignant melanoma M4 Beu (IC₅₀ ca 4.5 μM) versus normal cells (IC₅₀ ca 7.5 μM) suggests that, despite a lack of specificity for cancer cells, hederacolchisid A₁ has potential anti-tumor applications. Comparison of the cytotoxicity of hederacolchisid A₁ 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-α-L-rhamnopyranosyl (1 → 2)-α-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.

Hederacolchisid A₁ - Hedera colchica - Araliaceae - anti-tumor activity - α-hederin (kalopanaxsaponin A) - triterpene saponins - human melanoma M4 Beu - human carcinoma - structure-activity relationship (SAR)

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