In Vitro Anticancer Potential of <i>Jasione montana</i> and Its Main Components against Human Amelanotic Melanoma Cells
<i>Jasione montana</i> L. (Campanulaceae) is used in traditional Belarusian herbal medicine for sleep disorders in children, but the chemical composition and biological activity have not been investigated. In this study, the activities of <i>J. montana</i> extracts, their fra...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/7/3345 |
| Summary: | <i>Jasione montana</i> L. (Campanulaceae) is used in traditional Belarusian herbal medicine for sleep disorders in children, but the chemical composition and biological activity have not been investigated. In this study, the activities of <i>J. montana</i> extracts, their fractions and main compounds were evaluated in amelanotic melanoma C32 (CRL-1585) cells and normal fibroblasts (PCS-201-012). The extracts and fractions were analyzed using liquid chromatography–photodiode array detection–electrospray ionization–mass spectrometry (LC–PDA–ESI–MS/TOF) to characterize 25 compounds. Further, three major and known constituents, luteolin (<b>22</b>) and its derivatives such as 7-<i>O</i>-glucoside (<b>12</b>) and 7-<i>O</i>-sambubioside (<b>9</b>) were isolated and identified. The cytotoxic activities against fibroblasts and the amelanotic melanoma cell line were determined using the fixable viability stain (FVS) assay. The influence of diethyl ether (Et<sub>2</sub>O) fraction (<b>JM4</b>) and <b>22</b> on apoptosis induction was investigated using an annexin V binding assay. The obtained results showed significant cytotoxicity of <b>JM4</b> and <b>22</b> with IC<sub>50</sub> values of 119.7 ± 3.2 and 95.1 ± 7.2 μg/mL, respectively. The proapoptotic potential after <b>22</b> treatment in the C32 human amelanotic melanoma cell line was comparable to that of vinblastine sulfate (VLB), detecting 29.2 ± 3.0% apoptotic cells. Moreover, <b>22</b> displayed less necrotic potential against melanoma cells than VLB. In addition, the influences of <b>JM4</b> and <b>22</b> on the dysfunction of the mitochondrial membrane potential (MMP), cell cycle and activity of caspases 3, 8, 9, and 10 were established. The effects of <b>JM4</b> on MMP change (74.5 ± 3.0% of the cells showed a reduced MMP) corresponded to the results obtained from the annexin V binding assay and activation of caspase-9. <b>JM4</b> and <b>22</b> displayed a significant impact on caspase-9 (40.9 ± 2.4% of the cells contained active caspase-9 after <b>JM4</b> treatment and 16.6 ± 0.8% after incubation with <b>22</b>) and the intrinsic (mitochondrial) apoptotic pathway. Moreover, studies have shown that <b>JM4</b> and <b>22</b> affect the activation of external apoptosis pathways by inducing the caspase-8 and caspase-10 cascades. Thus, activation of caspase-3 and DNA damage via external and internal apoptotic pathways were observed after treatment with <b>JM4</b> and <b>22</b>. The obtained results suggest that <i>J. montana</i> extracts could be developed as new topical preparations with potential anticancer properties due to their promising cytotoxic and proapoptotic potential. |
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| ISSN: | 1661-6596 1422-0067 |