Britannin a Sesquiterpene Lactone from Inula aucheriana Exerted an Anti-leukemic Effect in Acute Lymphoblastic Leukemia (ALL) Cells and Enhanced the Sensitivity of the Cells to Vincristine.

Since chemotherapy drugs have dose-related side effects, there is still a need for finding new agents with suitable cytotoxic effects without any harmful effects. For this purpose, we evaluated the cytotoxic effects of Britannin that is a Sesquiterpene Lactone compound Inula aucheriana, alone or in combination with Vincristine (VCR), on Acute Lymphoblastic Leukemia (ALL)-derived MOLT-4 cells. In this study, we found that Britannin decreased the viability of MOLT-4 cells with the IC50 Values of 2 µM, but had no cytotoxic effects on normal cells or Peripheral Blood Mononuclear Cells (PBMCs). Our results also showed that Britannin decreased the proliferation of MOLT-4 cells by preventing the transition of the cells from the S phase of the cell cycle through the up-regulation of p21 and p27. Moreover, this agent induced ROS-mediated apoptosis by altering the expression of Bax, Bim, Caspase3, Bcl2, and XIAP. Britannin also produced a synergistic effect with Vincristine in MOLT-4 cells. Taken together, the results of this study showed for the first time that Britannin, as a natural Sesquiterpene Lactone, has cytotoxic effects that could be considered as an anti-leukemic agent in the treatment of ALL. However, there is still a demand for further studies that examine the efficacy and the safety of this purified compound.

The Overexpression of Sonic Hedgehog Associates with Collateral Development and Amelioration of Oxidative Stress in Stroke Patients.

PURPOSE: Sonic hedgehog (SHH) signaling pathway in oxidative stress condition has been acknowledged as a key trigger for angiogenesis and collateral vessel growth in the ischemic brain, and it exerts a protective effect on neuronal cells during oxidative stress. METHODS: A total of sixty patients (n = 30 good collateral profile and n = 30 poor collateral profile) diagnosed with acute cerebral ischemia were enrolled in this study. qRT-PCR was performed to analyze the expression levels of SHH, Gli1, and superoxide dismutase (SOD), genes. Also, the serum levels of oxidative stress markers were determined in experimental groups. RESULTS: The expression levels of SHH and Gli1 genes were significantly (p < 0.05) higher in stroke patients with good collateral circulation compared with those with poor collateral circulation, while SOD gene expression was similar between two groups (p > 0.05). A significantly positive correlation was found between the gene expression of SHH and Gli1 (r = 0.604, p < 0.001), SOD and Gli1 (r = 0.372, p < 0.003) genes. Our findings showed that the serum level of total antioxidant capacity (TAC) and Glutathione (GSH) and SOD enzyme activity was significantly (p < 0.05) increased, while serum total oxidant status (TOS) and malondialdehyde (MDA) levels were significantly (p < 0.05) decreased in patients with good collateral circulation as compared with those with poor collateral circulation. CONCLUSION: Our observations shed light on the association of the SHH/Gli1 signaling pathway with cerebral collateral vessel development following ischemia. Oxidative stress in stroke patients with poor collateral circulation may result in the overexpression of SHH/Gli1 signaling pathway which possibly contribute to oxidative stress attenuation, as well as modulate angiogenesis and collateral vessels development.

Triangle collaboration assessment of autophagy, ER stress and hypoxia in leukemogenesis: a bright perspective on the molecular recognition of B-ALL.

B-lineage acute lymphoblastic leukemia (B-ALL) is the most common acute leukemia in childhood and adults, which caused by many various crystalline and unclear agents. Owning to this matter, no significant progress has been made in the patients-recovery. Recently, autophagy pathway is considered as an ambiguous agent in leukemia evaluation. We aim to discover the expression levels of upstream autophagy-regulating genes in newly diagnosed B-ALL patients. In B-ALL group, BECN1, HIF1A and ERN1 expressions were significantly down-regulated, while BCL2 expression was up-regulated compared to the control group (p < .05). Moreover, there was significant positive correlation between the decreased BECN1 compared with Hypoxia and endoplasmic reticulum (ER) stress-related genes expression in the patients (p < .05). Our findings revealed that, ERN1 and ER stress pathway-related genes could be effective regulators of autophagy in B-ALL. More investigation is recommended to gain a deeper understanding into molecular pathophysiology of B-ALL to improve treatment and monitoring approaches in affected patients.