Capsaicin displays anti-proliferative activity against human small cell lung cancer in cell culture and nude mice models via the E2F pathway.
Capsaicin displays anti-proliferative activity against human small cell lung cancer in cell culture and nude mice models via the E2F pathway.
复制标题
DOI：
10.1371/journal.pone.0010243
复制
发表时间：
2010-04-20
期刊：
影响因子：
3.7
通讯作者：
Dasgupta P
中科院分区：
文献类型：
--
作者：
Brown KC;Witte TR;Hardman WE;Luo H;Chen YC;Carpenter AB;Lau JK;Dasgupta P
小细胞肺癌（SCLC）的特点是进展快、生存率低。因此，迫切需要针对该疾病的新型治疗剂。辣椒素是辣椒的活性成分，在体外对前列腺癌和表皮样癌具有抗增殖活性。然而，辣椒素的抗增殖活性尚未在人类 SCLC 中进行研究。本手稿填补了这一知识空白，并探讨了辣椒素在体外和体内 SCLC 中的抗增殖作用。 BrdU 测定和 PCNA ELISA 显示辣椒素在四种人类 SCLC 细胞系中表现出强大的抗增殖活性。此外，通过 CAM 测定和裸鼠模型证实，辣椒素在体内有效抑制 H69 人 SCLC 肿瘤的生长。我们研究的第二部分试图深入了解辣椒素抗增殖活性的分子机制。我们发现辣椒素的抗增殖活性与 E2F 响应性增殖基因（如细胞周期蛋白 E、胸苷酸合酶、cdc25A 和 cdc6）在 mRNA 和蛋白质水平上的表达降低相关。转录因子 E2F4 介导辣椒素的抗增殖活性。通过 siRNA 方法消除 E2F4 水平可抑制辣椒素诱导的 G1 期停滞。 ChIP 测定表明，辣椒素引起 E2F4 和 p130 在 E2F 响应性增殖启动子上的募集，从而抑制细胞增殖。我们的研究结果表明，辣椒素的抗增殖作用可能有助于治疗人类 SCLC。
Small cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays anti-proliferative activity in prostate and epidermoid cancer in vitro. However, the anti-proliferative activity of capsaicin has not been studied in human SCLCs. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo. BrdU assays and PCNA ELISAs showed that capsaicin displays robust anti-proliferative activity in four human SCLC cell lines. Furthermore, capsaicin potently suppressed the growth of H69 human SCLC tumors in vivo as ascertained by CAM assays and nude mice models. The second part of our study attempted to provide insight into molecular mechanisms underlying the anti-proliferative activity of capsaicin. We found that the anti-proliferative activity of capsaicin is correlated with a decrease in the expression of E2F-responsive proliferative genes like cyclin E, thymidylate synthase, cdc25A and cdc6, both at mRNA and protein levels. The transcription factor E2F4 mediated the anti-proliferative activity of capsaicin. Ablation of E2F4 levels by siRNA methodology suppressed capsaicin-induced G1 arrest. ChIP assays demonstrated that capsaicin caused the recruitment of E2F4 and p130 on E2F-responsive proliferative promoters, thereby inhibiting cell proliferation. Our findings suggest that the anti-proliferative effects of capsaicin could be useful in the therapy of human SCLCs.
登录
查看更多内容
影响因子：
4.7
作者：
Amantini, C.;Mosca, M.;Santoni, G.
通讯作者：
Santoni, G.
影响因子：
8
作者：
Ho, V. M.;Schaffer, B. E.;Karnezis, A. N.;Park, K. S.;Sage, J.
通讯作者：
Sage, J.
影响因子：
2.7
作者：
Danielian, Paul S.;Kim, Carla F. Bender;Lees, Jacqueline A.
通讯作者：
Lees, Jacqueline A.
影响因子：
64.5
作者：
CHELLAPPAN, SP;HIEBERT, S;NEVINS, JR
通讯作者：
NEVINS, JR
影响因子：
11.2
作者：
Kinkade, Rebecca;Dasgupta, Piyali;Chellappan, Srikumar
通讯作者：
Chellappan, Srikumar