Lclet 4 enhances pro-apoptotic and anti-invasive effects of mitoxantrone on human prostate cancer cells - in vitro study.

Abstract

Triterpene saponosides are widely distributed plant secondary metabolites characterized by relatively low systemic cytotoxicity and a range of biological activities. These include anti-inflammatory, antimicrobial, vasoprotective and antitumor properties. In particular, the ability of saponins to enhance the cytotoxicity of chemotherapeutic drugs opened perspectives for their application in combined cancer chemotherapy. Here, we used human prostate cancer DU-145 cells as an in vitro model to elucidate the synergy of the interactions between biological activities of an oleanane type 13β,28-epoxy triterpene saponoside (Lclet 4) and mitoxantrone, which is a cytostatic drug commonly used in prostate cancer therapy. No cytotoxic or pro-apoptotic effect of Lclet 4 and mitoxantrone administered at the concentrations between 0.05 and 0.1 µg/ml could be seen. In contrast, cocktails of these agents exerted synergistic pro-apoptotic effects, accompanied by the activation of the caspase 3/7 system. This effect was paralleled by attenuating effects of Lclet 4/mitoxantrone cocktails on the invasive potential, metalloproteinase expression and motility of DU-145 cells. Multifaceted and additive effects of Lclet 4 and mitoxantrone on basic cellular traits crucial for prostate cancer progression indicate that the combined application of both agents at systemically neutral concentrations may provide the basis for new promising strategies of prostate cancer chemotherapy.

Multidirectional effects of triterpene saponins on cancer cells - mini-review of in vitro studies

“…Little information is available about the effects of combined therapies on cancer invasion. Our study is one of the first reports on the impact of known cytostatic drug (mitoxantrone) combined with triterpene saponins (Lclet 4) isolated from Lysimachia clethroides on invasive activity of human prostate cancer cells (Koczurkiewicz et al, 2013B). The results show that the activity of Lclet 4/MTX was significantly higher than that of both substances used alone.…”

“…Saponin administration (Lclet 4) with mitoxantrone also resulted in inhibition of tumor cell transmigration. It is worth noting that the saponin Lclet 4 used individually, even at higher concentrations did not result in inhibition of tumor cell transmigration (Koczurkiewicz et al, 2013B). These data show that the combination anticancer drugs with saponins is a promising strategy of cancer treatment.…”

“…Both analyzed compounds (CIL 1 and CIL 2) inhibited invasion and induced apoptosis in prostate cancer cells while normal cells were insensitive to their action. Moreover, CIL 1 exerted a stronger effect on invasive human prostate cancer cells than on their less invasive counterparts (Koczurkiewicz et al, 2013B).…”

Saponins as chemosensitizing substances that improve effectiveness and selectivity of anticancer drug—Minireview of in vitro studies

“…Interestingly, normal PNT2 prostate cells were definitely less sensitive to MTX/Lclet4 action. This may indicate the effect of Lclet4 saponin on improving the selectivity of MTX, which is valuable from the perspective of reducing the side effects of chemotherapy (Koczurkiewicz et al, ).…”

Chemopreventive and Anticancer Activities of Bacopa Monnieri Extracted from Artificial Digestive Juices

“…To determine the anti-invasive effects of B. monnieri extracts on cancer cells, we further concentrated on their interference with the motile activity of DU 145 cells, a parameter crucial for cancer cell invasion. In vitro models of prostate cancer have previously been applied to identify the determinants of prostate cancer cell invasion [11]. The results show that all B. monnieri extracts (at a non-toxic concentration (5 µg/mL) inhibit cancer cell motility compared with control conditions, as illustrated by circular diagrams depicting DU 145 cell trajectories.…”