5 research outputs found
Perifosine and vitamin D combination induces apoptotic and non-apoptotic cell death in endometrial cancer cells
Endometrial cancer is the most common cancer of the female reproductive system. Combination treatment with specific agents has been widely used as a targeted therapy for cancer. In this study, we aimed to investigate the anti-proliferative and apoptotic effects of varying concentrations of perifosine and vitamin D on the human endometrial cancer cell line (HEC-1A). HEC-1A cells were exposed to perifosine (10 μM, 30 μM), vitamin D (50 nM, 200 nM) and combinations of both for 48 h and 72 h. Monitoring of cell proliferation in a time-dependent manner was performed with the xCELLigence RTCA DP system. The levels of BCL2, BAX and P53 mRNA expression were examined using RT-qPCR. Apoptosis was determined using Annexin V, which were followed by flow cytometry analysis. Ultra-structural morphology of cells was analyzed by transmission electron microscopy (TEM) for 72 h. The anti-proliferative and apoptotic effects of the perifosine+vitamin D combination (30 μM + 200 nM at 48 h and 10 μM + 200 nM at 72 h) on HEC-1A cells were higher than in perifosine and vitamin D alone. It was observed that perifosine has increased the expression of BAX mRNA in HEC-1A cells in a dose-dependent manner. While perifosine+vitamin D combinations increased P53 mRNA expression in HEC-1A cells we did not find any significant change in BCL2, BAX mRNA expression levels. In TEM examinations of HEC-1A cells, perifosine appeared to lead autophagic cell death, whereas vitamin D caused paraptosis-like cell death and combination of perifosine+vitamin D caused apoptotic and non-apoptotic (paraptotic, autophagic and necrotic) cell death. Therefore, it is considered that the combination of both drugs in the treatment of endometrial cancer might be an alternative and effective treatment option through activating the apoptotic and non-apoptotic cell death mechanisms in cancer cells
Role of rho-kinase (ROCK) in tonic but not phasic contraction in the frog stomach smooth muscle
Developmental Control and Plasticity of Fruit and Seed Dimorphism in Aethionema arabicum
Understanding how plants cope with changing habitats is a timely and
important topic in plant research. Phenotypic plasticity describes the
capability of a genotype to produce different phenotypes when exposed to
different environmental conditions. In contrast, the constant production
of a set of distinct phenotypes by one genotype mediates bet hedging, a
strategy that reduces the temporal variance in fitness at the expense of
a lowered arithmetic mean fitness. Both phenomena are thought to
represent important adaptation strategies to unstable environments.
However, little is known about the underlying mechanisms of these
phenomena, partly due to the lack of suitable model systems. We used
phylogenetic and comparative analyses of fruit and seed anatomy,
biomechanics, physiology, and environmental responses to study fruit and
seed heteromorphism, a typical morphological basis of a bet-hedging
strategy of plants, in the annual Brassicaceae species Aethionema
arabicum. Our results indicate that heteromorphism evolved twice within
the Aethionemeae, including once for themonophyletic annual Aethionema
clade. The dimorphism of Ae. arabicum is associated with several
anatomic, biomechanical, gene expression, and physiological differences
between the fruit and seed morphs. However, fruit ratios and numbers
change in response to different environmental conditions. Therefore, the
life-history strategy of Ae. arabicum appears to be a blend of bet
hedging and plasticity. Together with the available genomic resources,
our results pave the way to use this species in future studies intended
to unravel the molecular control of heteromorphism and plasticity