Anti-Cancer Agents in Medicinal Chemistry

Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear.

Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol’s malignance-modulating properties and the potential molecular mechanisms.

Read more here: http://www.eurekaselect.com/155527/article

20 Apr 2018

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Press Release – The clinical and experimental research on the treatment of endometriosis with thiostrepton

This article by Dr. Ping Jin et al. is published in Anti-Cancer Agents in Medicinal Chemistry, Volume 18, 2018

Forkhead Box M1 (FOXM1), which known as Trident, HNF-3, HFH-11, MPP2, and Win, is a transcriptional factor that plays an important role in cell proliferation, differentiation, and transformation. As one of the early up-regulated proteins in cancerogenesis, FOXM1 is frequently activated in tumors. This research studied the expression and the possible mechanism of FOXM1 and evaluated the effects of thiostrepton in an endometriotic rat model.

The research concluded two part. On the one hand, we constructed the rats model of endometriosis. Observed the expression of FOXM1 in endometriosis tissues. Explored the possible mechanism of FOXM1 action, like EKR?FOXM1 and MMP9 Signaling Pathway. Fifty female Wistar rats were surgically induced with endometriosis. After 4 weeks of observation, twenty and thirty rats were randomly allocated to an ovariectomized (OVX) group and a treatment group, respectively. The OVX group was ovariectomized and randomly divided into an OVX-estrogen group and a control (OVX -oil) group. All rats were allowed a resting period of 3 days prior to any operation. The rats in the estrogen group were given estradiol (20 μg/kg, 0.1 ml /d), while the control group was treated with an equivalent amount of sesame oil. Every group was injected with subcutaneous injection for 7 days. Our results showed that FOXM1 is enrich in nucleus of an ectopic endometrium when compared with an eutopic uterus. Furthermore, we found that an ERK/FOXM1/matrix metalloproteinase-9 (MMP9) signaling pathway might result in the establishment and development of endometriosis.

On the other hand, thiostrepton is a small-molecule inhibitor of the transcription factor FOXM1. We evaluated the effects of thiostrepton in an endometriotic rat model. The treatment group was randomly divided into three groups to receive the following: TST at 150 mg/kg, ip.; TST at 250 mg/kg, ip.; or sterile normal saline, ip. The groups received these dosages every 2 days for 2 weeks. Lesion growth, histological examination, and protein expression were subsequently analyzed using caliper measurement, histology, immunostaining, and Western blot after each rat received an injection in its own group. Our results showed that a thiostrepton concentration dependently reduced the expression of FOXM1, MMP9 and Bcl-2 in endometriotic lesions of the treated rats. Statistical significance was accepted for a value of P < 0.05.

In conclusion, we postulate that thiostrepton could inhibit the endometriotic lesions, at least in part, by decreasing the FOXM1 expression and exerting a pro-apoptotic effect. We reported for the first time that FOXM1 expresses in experimental endometriosis rat and thiostrepton may also be suitable for the administration of endometriosis by inhibiting the growth of endometriotic implants.

For more information, please visit: http://www.eurekaselect.com/158859

19 Apr 2018

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OPEN ACCESS ARTICLE – Regulation of Apoptosis by SYB in HepG2 Liver Cancer Cells is Mediated by the P53/Caspase 9 Axis – Anti-Cancer Agents in Medicinal Chemistry

Journal: Anti-Cancer Agents in Medicinal Chemistry

Author(s): Sharula, Zhongjun Wu*

Graphical Abstract:

Abstract:

Objective: To explore the function of miR-34a in promotion of apoptosis by SYB.

Methods: In this study, the most effective concentration of SYB was determined by measuring cell proliferation. Relative miR-34a mRNA levels were detected by quantitative RT-PCR. Apoptosis was assessed using Annexin- V/PI assays, whereas protein levels of p53, caspase 3, caspase 9, caspase 8 and Bcl2 were evaluated by western blotting.

Results: Minimum HepG2 cell growth was observed after 36h of exposure to 150 nmol/L SYB. miR-34a expression was highest 40min after the addition of SYB. SYB slightly decreased the abundance of Bcl-2, but increased the abundance of p53, caspase 3, caspase 9 and caspase 8. SYB failed to alter miR-34a expression when p53 was inhibited. Bcl-2 abundance remained low over time, whereas the abundance of caspase 3, caspase 9 and caspase 8 gradually increased. Inhibition of p53 promoted HepG2 cell growth in comparison with that of the control group. miR-34a was silenced to assess the role of miR-34a in the inhibitory effect of SYB on HepG2 cell growth. When p53 was silenced, protein abundance of Bcl2, caspase 3, caspase 8 and caspase 9 remained unchanged following the addition of SYB; moreover, HepG2 cell growth was increased.

Conlusion: SYB represents a promising therapeutic approach for liver cancer patients.

Read more here: http://www.eurekaselect.com/151132/article