Investigation of potential cytotoxicity and mutagenicity of guaianolides isolated from Chrysophthalmum montanum (DC.) Boiss

In research on natural compounds, medicinal plants belonging to the Asteraceae, containing sesquiterpene lactones, are being investigated for their cytotoxic activities leading to the development of new anticancer agents [1]. In this regard, in our previous study we investigated the cytotoxic activity of Chrysophthalmum montanum (DC.) Boiss. (Asteraceae) on human cancer cell lines [MCF 7, MDA-MB-231, PC3, and HT-29] using the SRB assay through bioassay-guided fractionation. We revealed that the active chloroform sub-extract led to guaianolide-type sesquiterpene lactones, namely 6α-acetoxy-4α-hydroxy-1βH-guaia-9.11(13)-dien-12.8α-olide (1), 6α-acetoxy-4α-hydroxy-9β.10β-epoxy-1βH-guaia-11(13)-en-12.8α-olide (2), 4α,6α-dihydroxy-1β,5α,7αH-guaia-9(10),11(13)-dien-12,8α-olide (3), and (4α,5α,8β,10β)-4,10-dihydroxy-1,11(13)-guaidien-12,8-olide (4). The guaianolides (1-4) exhibited significant growth inhibition, and 4 possessed strong cytotoxicity against HT-29 with high selectivity between cancer, and normal (BEAS-2B) cell lines [2]. In the continuation of this study, we aimed to evaluate the cytotoxic potential of these guaianolides against different human cancer cell lines, i.e. cervical (HeLa), and lung (A549), and a normal human cell line (BEAS-2B) using the MTT method. In addition, we firstly assessed their mutagenicities in silico by combining knowledge-based and statistical-based approaches. Among the tested compounds, 1, and 2 showed the strongest activities with IC₅₀ values of <4 µg/mL on HeLa, A549, and BEAS-2B. We also revealed that 1, 3, and 4 were non-mutagenic, while 2 was mutagenic. As a conclusion, this study firstly reported cytotoxicities of the isolated guaianolides against HeLa, and A549 cell lines, as well as their mutagenicities. Our results suggest that 1, and 2 can be regarded as promising candidates for discovering anticancer drugs, and determination of their cytotoxic mechanisms.

• References

• 1 Cheng XR, Ye J, Ren J, Zeng Q, Zhang F, Qin JJ, Shen YH, Zhang WD, Jin HZ. Terpenoids from Inula sericophylla Franch. and their chemotaxonomic significance. Biochem Syst Ecol 2012; 42: 75-78.
• 2 Ayaz F, Küçükboyacı N, Gören N, Çalış İ, Aydınlık Ş, Ulukaya E, Duman H, Choudhary MI. Bioassay-guided isolation of cytotoxic compounds from Chrysophthalmum montanum (DC.) Boiss., Food Chem Toxicol 2019; 125: 10-20.