The marine natural product Scalarin inhibits the receptor for advanced glycation end products (RAGE) and autophagy in the PANC-1 and MIA PaCa-2 pancreatic cancer cell lines.
The marine natural product Scalarin inhibits the receptor for advanced glycation end products (RAGE) and autophagy in the PANC-1 and MIA PaCa-2 pancreatic cancer cell lines.
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DOI：
10.1007/s10637-018-0635-4
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发表时间：
2019-04
影响因子：
3.4
通讯作者：
Wright AE
中科院分区：
文献类型：
--
作者：
Guzmán EA;Pitts TP;Diaz MC;Wright AE
胰腺癌是美国癌症死亡的第四大原因，预后不良，因为转移发生在症状出现之前。尽管联合疗法在治疗方面有所改善，但胰腺癌诊断后五年的生存率仅为8%，这强调了对新治疗方法的需求。晚期糖基化终末产物受体（AGEs）最近已成为KRAS驱动的胰腺癌治疗和化学预防的化疗靶点。胰腺癌是一种重要的炎症、应激和生存途径的调节因子，导致胰腺癌的致癌、化疗耐药、增殖增强和高转移潜能。胰腺癌肿瘤中有表达，但在邻近的上皮组织中没有表达。它的存在与增殖和转移增加有关。为了在我们收集的海洋来源的次级代谢产物中鉴定新的抑制剂，开发了利用流式细胞术的基于细胞的筛选测定。这一努力导致了scalarin作为活性化合物的海洋海绵鉴定为Eurypongia cf。玫瑰色。Scalarin是一种二倍半萜天然产物，以前从不同的海绵中分离出来。Scalarin降低PANC-1和MIA PaCa-2胰腺癌细胞系中的自噬水平并抑制自噬。在AsPC-1、PANC-1、MIA PaCa-2和BxPC-3胰腺癌细胞系中，其细胞毒性的IC 50范围为20-30 μM。自噬的抑制限制了胰腺癌的肿瘤生长和肿瘤发生，使Scalarin成为一种值得进一步研究的有趣化合物。
Pancreatic cancer, the fourth leading cause of cancer death in the United States, has a negative prognosis because metastasis occurs before symptoms manifest. Although combination therapies are showing improvements in treatment, the survival rate for pancreatic cancer five years post diagnosis is only 8%, stressing the need for new treatments. The receptor for advanced glycation end products (RAGE) has recently emerged as a chemotherapeutic target in KRAS driven pancreatic cancers both for treatment and in chemoprevention. RAGE appears to be an important regulator of inflammatory, stress and survival pathways that lead to carcinogenesis, resistance to chemotherapy, enhanced proliferation and the high metastatic potential of pancreatic cancer. RAGE expression has been demonstrated in pancreatic cancer tumors but not in adjacent epithelial tissues. Its presence is associated with increased proliferation and metastasis. In an effort to identify novel inhibitors of RAGE among our collection of marine-derived secondary metabolites, a cell-based screening assay utilizing flow cytometry was developed. This effort led to the identification of scalarin as the active compound in a marine sponge identified as Euryspongia cf. rosea. Scalarin is a sesterterpene natural product isolated previously from a different marine sponge. Scalarin reduces the levels of RAGE and inhibits autophagy in the PANC-1 and MIA PaCa-2 pancreatic cancer cell lines. Its IC50 for cytotoxicity ranges between 20–30 μM in the AsPC-1, PANC-1, MIA PaCa-2 and BxPC-3 pancreatic cancer cell lines. Inhibition of autophagy limits tumor growth and tumorigenesis in pancreatic cancer, making scalarin an interesting compound that may merit further study.
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影响因子：
12.4
作者：
Kang R;Tang D;Schapiro NE;Livesey KM;Farkas A;Loughran P;Bierhaus A;Lotze MT;Zeh HJ
通讯作者：
Zeh HJ
影响因子：
5.6
作者：
Lee, Yeon-Ju;Lee, Jeong-Woo;Yun, Jieun
通讯作者：
Yun, Jieun
影响因子：
5.1
作者：
Pettit, GR;Cichacz, ZA;Pettit, RK
通讯作者：
Pettit, RK
影响因子：
5.7
作者：
Fujii, Satoshi;Mitsunaga, Shuichi;Ochiai, Atsushi
通讯作者：
Ochiai, Atsushi
影响因子：
13.3
作者：
Dalby KN;Tekedereli I;Lopez-Berestein G;Ozpolat B
通讯作者：
Ozpolat B