RESUMO
Low-power laser irradiation (LPLI) is a non-invasive and safe method for cancer treatment that alters a variety of physiological processes in the cells. Autophagy can play either a cytoprotective role or a detrimental role in cancer cells exposed to stress. The detailed mechanisms of autophagy and its role on cytotoxicity in oral cancer cells exposed to LPLI remain unclear. In this study, we showed that LPLI at 810 nm with energy density 60 J/cm2 increased the number of microtubule associated protein 1 light chain 3 (MAP1LC3) puncta and increased autophagic flux in oral cancer cells. Moreover, reactive oxygen species (ROS) production was induced, which increased RelA transcriptional activity and beclin 1 (BECN1) expression in oral cancer cells irradiated with LPLI. Furthermore, ROS scavenger or knockdown of RelA diminished LPLI-induced BECN1 expression and MAP1LC3-II conversion. In addition, pharmacological and genetic ablation of autophagy significantly enhanced the effects of LPLI-induced apoptosis in oral cancer cells. These results suggest that autophagy may be a resistant mechanism for LPLI-induced apoptosis in oral cancer cells.
Assuntos
Autofagia , Proteína Beclina-1/metabolismo , Neoplasias Bucais/patologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição RelA/metabolismo , Humanos , Terapia com Luz de Baixa Intensidade , Neoplasias Bucais/imunologia , NF-kappa B/metabolismoRESUMO
Diallyl sulfide (1), diallyl disulfide (2), and diallyl trisulfide (3), which are major organosulfur compounds of garlic (Allium sativum), are recognized as a group of potential chemopreventive compounds. In this study, the early signaling effects of 3 were examined on Madin-Darby canine kidney (MDCK) cells loaded with the Ca(2+)-sensitive dye fura-2. It was found that 3 caused an immediate and sustained increase of [Ca(2+)](i) in a concentration-dependent manner (EC(50) = 40 µM). Compound 3 also induced a [Ca(2+)](i) elevation when extracellular Ca(2+) was removed, but the magnitude was reduced by 45%. In Ca(2+)-free medium, the 3-induced [Ca(2+)](i) level was abolished by depleting stored Ca(2+) with 1 µM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). Elevation of [Ca(2+)](i) caused by 3 in the Ca(2+)-containing medium was not affected by modulation of protein kinase C activity. The 3-induced Ca(2+) influx was inhibited by nifedipine and nicardipine (1 µM). U73122, an inhibitor of phospholipase C, abolished ATP (but not the 3-induced [Ca(2+)](i) level). These findings suggest that 3 induced a significant [Ca(2+)](i) elevation in MDCK renal tubular cells by stimulating both extracellular Ca(2+) influx and thapsigargin-sensitive intracellular Ca(2+) release via as yet unidentified mechanisms. Furthermore, the order of the allyl sulfide-induced [Ca(2+)](i) elevation and cell viability was 1 < 2 < 3. The differential effect of allyl sulfides on Ca(2+) signaling and cell death appears to correlate with the number of sulfur atoms in the structure of these allyl sulfides.
Assuntos
Compostos Alílicos/farmacologia , Cálcio/análise , Dissulfetos/farmacologia , Alho/química , Óleos Voláteis/química , Proteína Quinase C/metabolismo , Sulfetos/farmacologia , Trifosfato de Adenosina/metabolismo , Compostos Alílicos/química , Compostos Alílicos/isolamento & purificação , Animais , Cálcio/metabolismo , Morte Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Dissulfetos/química , Dissulfetos/isolamento & purificação , Retículo Endoplasmático/efeitos dos fármacos , Fase G2/efeitos dos fármacos , Rim/citologia , Rim/efeitos dos fármacos , Rim/metabolismo , Células Madin Darby de Rim Canino , Estrutura Molecular , Nicardipino/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Relação Estrutura-Atividade , Sulfetos/química , Sulfetos/isolamento & purificação , Fosfolipases Tipo C/antagonistas & inibidoresRESUMO
Diallyl disulfide (DADS), one of the major organosulfur compounds of garlic, is recognized as a group of potential chemopreventive compounds. In this study, we examines the early signaling effects of DADS on human colorectal cancer cells SW480 loaded with Ca(2+)-sensitive dye fura-2. It was found that DADS caused an immediate and sustained rise of [Ca(2+)](i) in a concentration-dependent manner (EC(50) = 232 µM). DADS also induced a [Ca(2+)](i) elevation when extracellular Ca(2+) was removed, but the magnitude was reduced by 45%. Depletion of intracellular Ca(2+) stores with 2 µM carbonylcyanide m-chlorophenylhydrazone, a mitochondrial uncoupler, didn't affect DADS's effect. In Ca(2+)-free medium, the DADS-induced [Ca(2+)](i) rise was abolished by depleting stored Ca(2+) with 1 µM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). DADS-caused [Ca(2+)](i) rise in Ca(2+)-containing medium was not affected by modulation of protein kinase C activity. The DADS-induced Ca(2+) influx was blocked by nicardipine (10 µM). U73122, an inhibitor of phospholipase C, abolished ATP (but not DADS)-induced [Ca(2+)](i) rise. These findings suggest that DADS induced a significant rise in [Ca(2+)](i) in SW480 colon cancer cells by stimulating both extracellular Ca(2+) influx and thapsigargin-sensitive intracellular Ca(2+) release via as yet unidentified mechanisms.
Assuntos
Compostos Alílicos/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Dissulfetos/farmacologia , Anticarcinógenos/farmacologia , Antioxidantes/farmacologia , Transporte Biológico/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/prevenção & controle , Alho/química , Variação Genética , Genótipo , HumanosRESUMO
A novel amide, cinnabutamine (1), along with five known amides, cinnaretamine (2), N-trans-caffeoyl-5-hydroxytyramine (3), N-trans-feruloyltyramine (4), N-trans-feruloyl-5-methoxytyramine (5) and N-cis-feruloyl-5-methoxytyramine (6), were isolated from the stems of Cinnamomum burmannii (Lauraceae). Their structures were characterized and identified by spectral analysis.
Assuntos
Amidas/química , Cinnamomum/química , Caules de Planta/química , Estrutura MolecularRESUMO
The cytotoxicity of hexahydrocurcumin and its effect on the cell cycle in human colorectal cancer cells SW480 has been studied for the first time. The compound, extracted from Zingiber officinale, was shown to be cytotoxic to colorectal cancer cells. Treatment of SW480 cells with hexahydrocurcumin (100 microM) resulted in a massive accumulation of the cells in the G1/G0 phase of the cell cycle. The cytotoxic effect of hexahydrocurcumin may prove useful in cancer prevention.
Assuntos
Antineoplásicos Fitogênicos/análise , Ciclo Celular/efeitos dos fármacos , Curcumina/análogos & derivados , Curcumina/farmacologia , Zingiber officinale/química , Linhagem Celular Tumoral , Curcumina/química , Ensaios de Seleção de Medicamentos Antitumorais , HumanosRESUMO
Diallyl sulfide (DAS), one of the major organosulfur compounds (OSCs) of garlic, is recognized as a group of potential chemoproventive compounds. In this study, we examines the early signaling effects of DAS on renal cells loaded with Ca(2+)-sensitive dye fura-2. It was found that DAS caused an immediate and sustained rise of [Ca(2+)](i) in a concentration-dependent manner (EC(50)=2.32 mM). DAS also induced a [Ca(2+)](i) elevation when extracellular Ca(2+) was removed, but the magnitude was reduced by 45%. Depletion of intracellular Ca(2+) stores with CCCP, a mitochondrial uncoupler, did not affect DAS's effect. In Ca(2+)-free medium, the DAS-induced [Ca(2+)](i) rise was abolished by depleting stored Ca(2+) with thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). DAS-caused [Ca(2+)](i) rise in Ca(2+)-containing medium was not affected by modulation of protein kinase C activity. The DAS-induced Ca(2+) influx was blocked by nicardipine. U73122, an inhibitor of phospholipase C, abolished ATP (but not DAS)-induced [Ca(2+)](i) rise. Additionally, pretreatment with DAS for 24 h decreased cell viability in a concentration-dependent manner. Furthermore, DAS-induced cell death involved apoptotic events. These findings suggest that diallyl sulfide induced a significant rise in [Ca(2+)](i) in MDCK renal tubular cells by stimulating both extracellular Ca(2+) influx and thapsigargin-sensitive intracellular Ca(2+) release via as yet unidentified mechanisms.
Assuntos
Compostos Alílicos/farmacologia , Antioxidantes/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Alho/química , Túbulos Renais/efeitos dos fármacos , Sulfetos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Sinalização do Cálcio/fisiologia , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cães , Relação Dose-Resposta a Droga , Estrenos/farmacologia , Corantes Fluorescentes/metabolismo , Fura-2/metabolismo , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Nicardipino/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Pirrolidinonas/farmacologia , Tapsigargina/farmacologia , Fosfolipases Tipo C/antagonistas & inibidores , Fosfolipases Tipo C/metabolismo , Desacopladores/farmacologiaRESUMO
[6]-gingerol, a major phenolic compound derived from ginger (Zingiber officinale), is a potential chemopreventive compound that can induce stress in cancer cells and cause apoptotic cell death. This study examines the early signaling effects of [6]-gingerol on renal cells. It was found that [6]-gingerol caused a slow and sustained rise of [Ca2+]i in a concentration-dependent manner. [6]-gingerol also induced a [Ca2+]i rise when extracellular Ca2+ was removed, but the magnitude was reduced by 80%. Depletion of intracellular Ca2+ stores with CCCP, a mitochondrial uncoupler, did not affect the action of [6]-gingerol. In a Ca2+-free medium, the [6]-gingerol-induced [Ca2+]i rise was partially abolished by depleting stored Ca2+ with thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). The elevation of [6]-gingerol-caused [Ca2+]i in a Ca2+-containing medium was not affected by modulation of protein kinase C activity. The [6]-gingerol-induced Ca2+ influx was blocked by nicardipine. U73122, an inhibitor of phospholipase C, abolished ATP (but not [6]-gingerol)-induced [Ca2+]i rise. These findings suggest that [6]-gingerol induces a significant rise in [Ca2+]i in MDCK renal tubular cells by stimulating both extracellular Ca2+ influx and thapsigargin-sensitive intracellular Ca2+ release via as yet unidentified mechanisms.
Assuntos
Anticarcinógenos/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Álcoois Graxos/farmacologia , Plantas Medicinais/química , Tapsigargina/farmacologia , Zingiber officinale/química , Animais , Anticarcinógenos/química , Catecóis , Cães , Álcoois Graxos/química , Rim/citologia , Rim/efeitos dos fármacos , Estrutura Molecular , Nicardipino/farmacologia , TaiwanRESUMO
Two new butanolides, subamolide D (1) and subamolide E (2), and a new secobutanolide, secosubamolide A (3), along with 21 known compounds were isolated from the leaves of Cinnamomum subavenium. The structures of 1-3 were determined by spectroscopic analysis. Propidium iodide staining and cytometry analysis were used to evaluate the cell cycle progression of the treated SW480 cells and it was found that 1 and 2 caused DNA damage in a dose- and time-dependent manner.