Abstract
Maslinic acid (MA) is a triterpenoid with a high concentration that exists in olives. This natural compound, which has shown multiple biological activities, was proved to be an anti-tumoral agent more recently. We have investigated the mechanisms of MA with regard to its inhibitory effects on the growth of salivary gland adenoid cystic carcinoma (ACC). We demonstrated that MA at 10–100 μM reduced cell viability in a dose-dependent manner, IC50 of 43.68 μM, and 45.76 μM, respectively in cultured ACC-2 and ACC-M cells. Fifty micromolars of MA efficiently induced apoptosis as indicated by AO/EB staining, electronic microscopy, flow cytometry, and activation of caspase-3 activity. MA induced an elevation of [Ca2+]i in a dose-dependent manner, and cell viability inhibition and cell apoptosis induced by MA were blocked by an intracellular Ca2+ chelator, BAPTA-AM. The elevation of [Ca2+]i induced by MA was blocked by EGTA or TRPV channel inhibitor suggesting TRPV channel involved in calcium influx induced by MA. MA also activated ERK and p38 MAPK in a time-dependent manner. MA induced cell apoptosis and activation of caspase-3 activity were reversed by SB203580, but not by PD98059, suggesting that the apoptosis induction of MA was via p38 MAPK, but not via ERK. Chelation of intracellular Ca2+ with BAPTA reversed MA induced p38 MAPK phosphorylation, but SB203580 did not block MA-evoked elevation of [Ca2+]i, suggesting a Ca2+-evoked p38 MAPK signaling involved in MA-induced apoptosis in ACC cells. Taken together, in ACC cells, maslinic acid induced an increase in [Ca2+]i, which evoked p38 MAPK phosphorylation, subsequently activated caspase-3 leading to apoptosis.
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This study was supported by the Initiative Scientific Research Foundation for Postdoctor Back to Heilongjiang Province (LBH-Q09045) and the Natural Science Foundation of China (30900575).
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Wu, DM., Zhao, D., Li, DZ. et al. Maslinic acid induces apoptosis in salivary gland adenoid cystic carcinoma cells by Ca2+-evoked p38 signaling pathway. Naunyn-Schmied Arch Pharmacol 383, 321–330 (2011). https://doi.org/10.1007/s00210-011-0598-x
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DOI: https://doi.org/10.1007/s00210-011-0598-x