RESUMEN
The chloroform extract of the Japanese cypress Chamaecyparis obtusa was found to kill PANC-1 human pancreatic cancer cells preferentially in the nutrient-deprived medium without causing toxicity in the nutrient rich condition. Phytochemical investigation on this extract led to the isolation of a new sesquiterpene (1), together with the six sesquiterpenes (2-7) and a lignan (8). The isolated compounds were tested for their preferential cytotoxicity activity against five different human pancreatic cancer cell lines [PANC-1, MIA PaCa2, CAPAN-1, PSN-1, and KLM-1] by utilizing an antiausterity strategy. Among them, α-cadinol (2) was identified as the most active constituent. α-Cadinol (2) was found to inhibit the activation of Akt/mTOR pathway, and the hyperactivation of autophagy leading to preferential PANC-1 cell death during nutrient-starvation.
Asunto(s)
Antineoplásicos Fitogénicos/química , Chamaecyparis/química , Ciclodecanos/química , Sesquiterpenos/química , Terpenos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/toxicidad , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Chamaecyparis/metabolismo , Ciclodecanos/aislamiento & purificación , Ciclodecanos/toxicidad , Evaluación Preclínica de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Espectroscopía de Resonancia Magnética , Microscopía Fluorescente , Conformación Molecular , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/toxicidad , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Terpenos/aislamiento & purificación , Terpenos/toxicidadRESUMEN
AIM: The aim of the present work was to purify and characterize potential natural antibacterial compound from mango ginger (Curcuma amada Roxb.) rhizome. METHODS AND RESULTS: The mango ginger rhizome powder was sequentially extracted and screened for antibacterial activity by agar well diffusion method and broth dilution method. Nonpolar extracts of mango ginger showed high antibacterial activity against gram-positive bacteria with low minimum inhibitory concentration (60-180 ppm). Among five extracts of mango ginger, the chloroform extract demonstrated highest antibacterial activity. Antibacterial activity-guided fractionation of the chloroform extract by repeated silica gel column chromatography yielded pure compound. The purified antibacterial compound was analysed by UV, IR, LC-MS and 2D-HMQCT NMR spectra and was identified as a difurocumenonol, a novel compound not reported previously. CONCLUSIONS: Mango ginger extracts and isolated difurocumenonol demonstrated high antibacterial activity against gram-negative and gram-positive bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel and natural antibacterial compound as well as mango ginger extracts can be used as food preservative to control the growth of food-borne pathogens and as a source of mango flavour.