## 5 Bioactivity of Secondary Metabolites in the _Leontopodium_ Taxa
### Anti-Tumoral Activity  
The cytotoxic activities of three new bisabolene sesquiterpenes from _L. longifolium_ roots extracts were assessed against two tumour cell lines: SMMC-7721 (human hepatoma) \begin{table}
\begin{tabular}{c c c c c} \hline
**Taxon/Extract/Bioactive Compound(s)** & **Experimental Model** & **Effects/Applied Tests** & **Ref.** \\ \hline  & & - & cytotoxic effects on 7 cancer & \\  & & Tumor cell lines of breast & - & significantly reduced viability of \\ _L. alpinum_ & (MCE-7, MDA-MB-231, & SK-MES-1, MDA-MB-23, H1792 & \\ - & extracts from callus culture & MDA-MB-468, HS578T), prostate (22 RV1 and & and HS578T cell lines, & \\  & & LNCaP), colon (DLD-1, & for SK-MES-1, MDA-MB-231 and & \\  & & HCT-116) and lung (H1792, & HS578T lines, & \\  & & SK-MES-1) cancers & - & inhibited the development of new & \\  & & & colonies in all tumour lines. & \\ \hline \multicolumn{4}{l}{Antidiabetic activity} \\ \hline  & & Alloxan or & & \\  & adrenaline-induced & - & hypoglycaemic effect & [91] \\ _L. leontopodioides_ & & diabetic Kunming mice & & \\ - & whole plants decoction & & & \\  & HepG2 line & - & reduced the levels of blood glucose, & \\  & & HepG2 line & cholesterol and triglycerides and & [125] \\  & & & increased the insulin level & \\ \hline - & ethanolic extract & Hyperglycaemic mice & - & reduced the levels of blood glucose & [126] \\ \hline - & luteolin derivative and & Ex vitro assay of & - & potent inhibitors & [85] \\  & lignan glucoside & \(\alpha\)-glucosidase activity & & \\ \hline - & aqueous and hydroalcoholic & & & \\  & extracts, & & & \\  & leontoerialosides D and E. & & & \\ \hline \multicolumn{4}{l}{Hepatoprotective/Chemoprotective activity} \\ \hline _L. leontopodioides_ & D-GalN-induced liver & - & positive effects on AST, ALT levels & \\ - & aqueous extract & injury in mice & and histopathological alterations & [127] \\  & HL-7702 line & & & \\ \hline _L. alpinum_ & PHK with sirtuin-induced & - & inhibited cell cycle, & \\ - & callus culture extract & senescence and restored by & - & proliferation and apoptosis, & \\ - & leontopodic acid & trichostatin A (inhibitor of & - & inhibited expression of p53 & [12] \\  & & sirtuin) treatment & - & and caspase 3. & \\ \hline \end{tabular}
\end{table} 
Table 5: _Cont._and HL-60 (human promyelocytic leukaemia) [38]. The results showed that two of the three bisabolene derivatives exerted moderate cytotoxic effects (IC\({}_{50}\) = 81.2 \(\mathrm{\SIUnitSymbolMicro g}\)/mL and IC\({}_{50}\) = 88.6 \(\mathrm{\SIUnitSymbolMicro g}\)/mL, respectively) but only on the HL-60 cell line. The effects of the essential oils from aerial parts of \(L\). _leontopodioides_ were investigated on HepG2 (liver hepatocellular) and MCF-7 (human breast adenocarcinoma) cell lines using the MTT assay [36]. The essential oil extract had a cytotoxic effect on HepG2 (IC\({}_{50}\) = 67.44 \(\pm\) 5.08 \(\mathrm{\SIUnitSymbolMicro g}\)/mL) and MCF-7 (IC\({}_{50}\) = 70.49 \(\pm\) 3.8 \(\mathrm{\SIUnitSymbolMicro g}\)/mL) cell lines after 72 h exposure. A novel norsesquiterpene, longifolactone, was isolated from \(L\). _longifolium_ roots, and its cytotoxicity was assessed against two human cancer lines, HepG2 and HeLa [35]. The results of this study showed that this compound exhibited weak cytotoxic effects on the tested human cancer cell lines. Among the curative effects of \(L\). _alpinum_ plants, ethnobotanical treatises mention using them against breast cancer [65], but the first research which highlighted the antiproliferative activity of a methanolic extract of \(L\). _alpinum_ callus culture on ten tumour cell lines characteristic of breast (MCF-7, MDA-MB-231, MDA-MB-468 and HS578T lines), prostate (22 RV1 and LNCaP), colon (DLD-1, HCT-116 lines) and lung cancer (H1792, SK-MES-1 lines) was quite recent [37].