Doramectin Induces Apoptosis in B16 Melanoma Cells.

IF 2.6 4区 医学 Q3 CHEMISTRY, MEDICINAL Anti-cancer agents in medicinal chemistry Pub Date : 2024-10-15 DOI:10.2174/0118715206325844240909144543
Megan S Crotts, Jena C Jacobs, Robert W Baer, James L Cox
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Abstract

Introduction/objective: Metastatic melanoma resists current pharmacological regimens that act through apoptosis. This indicates that therapies acting via non-apoptotic cell-death pathways could be pursued. Doramectin has shown promising results in another cancer of neural crest origin, neuroblastoma, through the inhibition of growth via autophagy. Our research hypothesis is that doramectin induces autophagy in B16F10 melanoma cells.

Methods: Cells were treated with doramectin (15 uM) or a combination of both doramectin and a cell-death inhibitor, compared to untreated control cells (media), and then analyzed with MTT analysis. Likewise, MDC analysis was completed to detect autophagy involvement with doramectin treatment. Flow cytometry and TUNEL Assay were conducted to observe cell death-related effects.

Results: MTT analysis of doramectin-treated cells displayed a decrease in cell growth compared to control. Apoptotic morphology was prominent in melanoma cells treated with doramectin. Increased autophagy was not detected by fluorometric microscopic analysis. Flow cytometry analysis of doramectin-treated cells showed apoptosis as a major mode of cell death with some necrosis.

Conclusion: Doramectin induces a novel cell-death mechanism in melanoma compared to other forms of cancer and should be studied as an effective anti-cancer agent for melanoma treatment.

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多拉菌素诱导 B16 黑色素瘤细胞凋亡
导言/目的:转移性黑色素瘤对目前通过细胞凋亡发挥作用的药物疗法有抵抗力。这表明,可以寻求通过非凋亡性细胞死亡途径发挥作用的疗法。多拉菌素通过自噬抑制生长,在另一种起源于神经嵴的癌症--神经母细胞瘤中显示出良好的效果。我们的研究假设是多拉菌素能诱导 B16F10 黑色素瘤细胞自噬:方法:用多拉菌素(15 uM)或多拉菌素与细胞死亡抑制剂的组合处理细胞,与未经处理的对照细胞(培养基)进行比较,然后用 MTT 分析。同样,还完成了 MDC 分析,以检测多拉菌素处理对自噬的影响。流式细胞术和 TUNEL 分析用于观察与细胞死亡相关的效应:结果:与对照组相比,多拉菌素处理过的细胞的 MTT 分析显示细胞生长有所下降。多拉菌素处理的黑色素瘤细胞凋亡形态明显。荧光显微分析未检测到自噬增加。多拉菌素处理过的细胞的流式细胞术分析表明,细胞凋亡是细胞死亡的主要方式,也有一些细胞坏死:多拉菌素诱导黑色素瘤细胞死亡的机制与其他形式的癌症相比具有新颖性,应将其作为治疗黑色素瘤的有效抗癌剂进行研究。
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来源期刊
Anti-cancer agents in medicinal chemistry
Anti-cancer agents in medicinal chemistry ONCOLOGY-CHEMISTRY, MEDICINAL
CiteScore
5.10
自引率
3.60%
发文量
323
审稿时长
4-8 weeks
期刊介绍: Formerly: Current Medicinal Chemistry - Anti-Cancer Agents. Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents. Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication. Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.
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