Apoptosis‐like, reversible changes in plasma membrane asymmetry and permeability, and transient modifications in mitochondrial membrane potential induced by curcumin in rat thymocytes

Abstract

Curcumin (diferuoylmethane) is a natural compound with anticareinogenic activities which is able to exert either proapoptotic or antiapoptotic effects in different cell types. This paper focuses on the sequence and extent of primary events induced by curcumin, in comparison with those occurring during dexamethasone-induced apoptosis in rat thymocytes. It also presents annexin VI-FITC as a new probe for studying membrane asymmetry. Curcumin readily penetrates into the cytoplasm, and is able to accumulate in membranous structures such as plasma membrane, endoplasmic reticulum and nuclear envelope. Curcumin-treated cells exhibit typical features of apoptotic cell death, including shrinkage, transient phosphatidylserine exposure, increased membrane permeability and decrease in mitochondrial membrane potential. However, nuclei morphology, DNA fragmentation, the extent and time-course of membrane changes are different from those observed during dexamethasone-induced apoptosis, suggesting that, despite many similarities, the mode of action and the events triggered by cnrcumin are different from those occurring during typical apoptosis.© In this paper, we analyzed the primary effects of the presence of CUR in rat thymocytes, and compared the sequence and extent of CUR-evoked events with those occurring during the typical apoptotic program induced by dexamethasone (DEX). The fluorescence and lipophilic properties of CUR [12] provided the basis for the search of its cellular localization and for analyzing the local effects on the structure and function of cellular membranes. Plasma membrane asymmetry was studied by a new fluorescence probe, i.e. annexin VI (Anx VI), isolated from porcine liver and coupled with FITC. We could investigate other parameters such as plasma membrane permeability, mitochondrial membrane potential, as well as other typical apoptotic features ,i.e. changes in cell volume, nucleus morphology and DNA fragmentation. Materials and methods

Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration

“…In addition, CUR in the medium (apical side) rapidly degraded ( Figure 9C). These results are similar to previous studies [40][41][42] and most likely occurred due to rapid cellular uptake of CUR from the medium and/or CUR degradation in the medium.…”

Antitumor activity of curcumin is mediated through the induction of apoptosis in AK‐5 tumor cells

“…Similar observations were made during curcumin induced apoptosis in human leukemic cells [22]. Curcumin also increased the level of glutathione which would prevent thiol depletion occurring during apoptosis [6]. Thus the role of curcumin in redox balance needs further investigation.…”

Carboplatin resistant human laryngeal carcinoma cells are cross resistant to curcumin due to reduced curcumin accumulation

“…Our results showed that there was no difference in membrane fatty acid composition between 7T and HEp-2 cells. We must point out that in our experiments we extracted lipids from whole cells, because curcumin can accumulate not only in plasma membrane, but also in membranes of endoplasmic reticulum and nuclear envelope (Jaruga et al, 1998). Therefore, we can not exclude some differences in fatty acid composition between membranes of different cell compartments.…”

“…Curcumin is a lipophilic compound, unstable in aqueous solutions (Wang et al, 1997), In the study on rat thymocytes it was shown that such properties enable this molecule to easily 14 14 enter the cell and localize in the membrane regions like: plasma membrane, membranes of endoplasmic reticulum and nuclear envelope (Jaruga et al, 1998). In one of the recent papers it was found that, except for membrane localization, minor nuclear localization occurred in mouse spleen lymphocytes, mouse fibroblast (NIH3T3), T cell lymphoma of murine origin (EL4) and breast cancer cell line of human origin (MCF7) (Kunwar et al, 2008).…”