Neo-tanshinlactone D-ring modified novel analogues induce apoptosis in human breast cancer cell via DNA damage

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• 作者：Biswadip Banerji^a ; ^b ; ; Sunil Kumar Killi^a ; ^&dagger ; ; Atul Katarkar^c ; ^&dagger ; ; Satadru Chatterjee^a ; Yellaiah Tangella^a ; Chandraday Prodhan^c ; Keya Chaudhuri^c
• 关键词：Neotanshinlactone ; γH2AX foci ; DNA damage ; HDAC ; Apoptosis
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：25
• 期：1
• 页码：202-212
• 全文大小：2275 K
• 卷排序：25

文摘

Neo-tanshinlactone (NTL) a natural product is known for its specificity and selectivity towards the breast cancer cells. By NTL D-ring modification approach, 13 new analogues were synthesized (1A–1M). Among them 1J showed the best anticancer activity in MCF-7 (ER+, PR+/−, HER2−), SKBR3 (ER−, PR−, HER2+) and MDA-MB-231 (ER−, PR−, HER2−) cells lines with IC50 value 11.98 nM, 23.71 nM, and 62.91 nM respectively. 1J showed minor grove binding interaction with DNA at AT-rich region and induced DNA double strand breaks (DDSBs). This had triggered several key molecular events involving, activation of ATM, Chk2 and p53, reduction in mitochondrial potential (Δψm) leading to caspase-3 and PARP cleavage mediated apoptosis. These results along with other biochemical studies strongly suggest that novel NTL analogue 1J caused DNA cleavage mediated apoptosis in the breast cancer cells and this may serve as potential lead for future breast cancer treatment.