当前位置：
X-MOL 学术
›
RSC Med. Chem.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Small molecule-mediated induction of endoplasmic reticulum stress in cancer cells
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2021-07-15 , DOI: 10.1039/d1md00095k Shalini Pandey 1, 2 , Virender Kumar Sharma 3 , Ankur Biswas 1 , Mayurika Lahiri 3 , Sudipta Basu 2
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2021-07-15 , DOI: 10.1039/d1md00095k Shalini Pandey 1, 2 , Virender Kumar Sharma 3 , Ankur Biswas 1 , Mayurika Lahiri 3 , Sudipta Basu 2
Affiliation
|
The endoplasmic reticulum (ER) is one of the crucial sub-cellular organelles controlling myriads of functions including protein biosynthesis, folding, misfolding and unfolding. As a result, dysregulation of these pathways in the ER is implicated in cancer development and progression. Subsequently, targeting the ER in cancer cells emerged as an interesting unorthodox strategy in next-generation anticancer therapy. However, development of small molecules to selectively target the ER for cancer therapy remained elusive and unexplored. To address this, herein, we have developed a novel small molecule library of sulfonylhydrazide-hydrazones through a short and concise chemical synthetic strategy. We identified a fluorescent small molecule that localized into the endoplasmic reticulum (ER) of HeLa cells, induced ER stress followed by triggering autophagy which was subsequently inhibited by chloroquine (autophagy inhibitor) to initiate apoptosis. This small molecule showed remarkable cancer cell killing efficacy in different cancer cells as mono and combination therapy with chloroquine, thus opening a new direction to illuminate ER-biology towards the development of novel anticancer therapeutics.
中文翻译：
小分子介导的癌细胞内质网应激诱导
内质网（ER）是重要的亚细胞细胞器之一，控制着蛋白质生物合成、折叠、错误折叠和解折叠等多种功能。因此，内质网中这些通路的失调与癌症的发生和进展有关。随后，靶向癌细胞中的 ER 成为下一代抗癌治疗中一种有趣的非正统策略。然而，开发选择性靶向 ER 进行癌症治疗的小分子仍然难以捉摸且尚未探索。为了解决这个问题，我们通过简短的化学合成策略开发了一种新型的磺酰肼-腙小分子库。我们鉴定出一种荧光小分子，定位于 HeLa 细胞的内质网 (ER)，诱导 ER 应激，随后触发自噬，随后被氯喹（自噬抑制剂）抑制以引发细胞凋亡。这种小分子与氯喹单药或联合治疗对不同癌细胞表现出显着的杀伤功效，从而为内质网生物学开发新型抗癌疗法开辟了新方向。
更新日期：2021-08-16
中文翻译：
小分子介导的癌细胞内质网应激诱导
内质网（ER）是重要的亚细胞细胞器之一，控制着蛋白质生物合成、折叠、错误折叠和解折叠等多种功能。因此，内质网中这些通路的失调与癌症的发生和进展有关。随后，靶向癌细胞中的 ER 成为下一代抗癌治疗中一种有趣的非正统策略。然而，开发选择性靶向 ER 进行癌症治疗的小分子仍然难以捉摸且尚未探索。为了解决这个问题，我们通过简短的化学合成策略开发了一种新型的磺酰肼-腙小分子库。我们鉴定出一种荧光小分子，定位于 HeLa 细胞的内质网 (ER)，诱导 ER 应激，随后触发自噬，随后被氯喹（自噬抑制剂）抑制以引发细胞凋亡。这种小分子与氯喹单药或联合治疗对不同癌细胞表现出显着的杀伤功效，从而为内质网生物学开发新型抗癌疗法开辟了新方向。
京公网安备 11010802027423号