RESUMEN
A naturally occurring stilbene, resveratrol, shows promising effects in the treatment of malignant pleural mesothelioma (MPM) both as a single agent and in combination with chemotherapeutic drugs. To discover new anticancer agents targeting MPM, stilbene-targeted isolation was performed on the roots of Polygonum multiflorum Thunb., an herbal medicine rich in stilbene compounds. In this study, seven stilbene glycosides (1-7) were isolated, along with four non-stilbenes (8-11), of which compounds 4 and 9-11 have not previously been isolated from this species. Stiquinoside A (1) is a previously undescribed stilbene glycoside, and its structure was elucidated as (E)-2,3,5,4'-tetrahydroxystilbene 2-O-ß-d-quinovopyranoside based on 1D and 2D-NMR, HR-ESI-MS, and acid hydrolysis experiments. Compounds 1, 4, 6, and 8 significantly inhibit the growth of MPM cancer cells H2452. These results demonstrate the potential utility of stilbenes in new strategies for the treatment of MPM.
Asunto(s)
Antineoplásicos Fitogénicos , Fallopia multiflora , Mesotelioma Maligno , Raíces de Plantas , Estilbenos , Humanos , Estilbenos/farmacología , Estilbenos/aislamiento & purificación , Raíces de Plantas/química , Estructura Molecular , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Mesotelioma Maligno/tratamiento farmacológico , Fallopia multiflora/química , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Glicósidos/farmacología , Glicósidos/aislamiento & purificación , Mesotelioma/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , ChinaRESUMEN
Neuroblastoma, a prevalent extracranial solid tumor in children, arises from undifferentiated nerve cells. While tumor vasculature, often characterized by increased permeability, influences metastasis and recurrence, the direct impact of blood-borne molecules on tumor progression remains unclear. In the present study, we focused on the effect of exposure to albumin, one of the most abundant proteins in the serum, on human neuroblastoma cells. Albumin exposure elevated oxidative stress and led to mitochondria dysfunction via the activation of TGFß and PI3K pathways, accompanied by an increase in the metastatic and invasive properties of neuroblastoma cells. Proteins relevant to the induction of autophagy were upregulated in response to prolonged albumin exposure. Additionally, pre-exposure to albumin before treatment resulted in increased resistance to paclitaxel. Two valeriana-type iridoid glycosides, patrisophoroside and patrinalloside, recently isolated from Nardostachys jatamansi significantly mitigated the effect of albumin on oxidative stress, cell invasiveness, and chemoresistance. These findings illuminate the potential role of blood-borne molecules, such as albumin, in the progression and metastasis of neuroblastoma, as well as the possible therapeutic implications of valeriana-type iridoid glycosides in anti-cancer treatment.
Asunto(s)
Resistencia a Antineoplásicos , Glicósidos Iridoides , Neuroblastoma , Paclitaxel , Humanos , Neuroblastoma/patología , Neuroblastoma/metabolismo , Neuroblastoma/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Paclitaxel/farmacología , Glicósidos Iridoides/farmacología , Línea Celular Tumoral , Invasividad Neoplásica , Estrés Oxidativo/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Valeriana/química , Albúmina Sérica/metabolismoRESUMEN
[This corrects the article DOI: 10.1021/acsomega.2c05415.].
RESUMEN
Twenty-one angular dihydropyranocoumarins and a linear furanocoumarin, including four previously undescribed compounds (1-4), were isolated from the flowers of Peucedanum japonicum (Umbelliferae). The structures of 1-4, along with their absolute stereochemistry, were determined to be (3'S,4'S)-3'-O-propanoyl-4'-O-(3â´-methyl-2â´-butenoyl)khellactone (1), (3'S,4'S)-3'-O-propanoyl-4'-O-(2â´-methyl-2â´Z-butenoyl)khellactone (2), (3'S,4'S)-3'-O-propanoyl-4'-O-(2â´-methylbutanoyl)khellactone (3), and (3'S,4'S)-3'-O-(2â³-methylpropanoyl)-4'-O-(3â´-methyl-2â´-butenoyl)khellactone (4) using one- and two-dimensional nuclear magnetic resonance, high-resolution electrospray ionization mass spectroscopy, and electronic circular dichroism spectroscopy. In addition, the absolute configuration of the three angular dihydropyranocoumarins (5-7) was determined for the first time in this study. Among the previously reported compounds isolated in this study, 8 and 9 were isolated for the first time from the genus Peucedanum, whereas 10 and 11 were previously unreported and had not been isolated from P. japonicum to date. Furthermore, all isolated compounds were evaluated for their aldo-keto reductase 1C1 inhibitory activities on A549 human non-small-cell lung cancer cells. Compounds 10 and 12 exhibited substantial AKR1C1 inhibitory activities with IC50 values of 35.8 ± 0.9 and 44.2 ± 1.5 µM, respectively.