A new protoapigenone analog RY10-4 induces apoptosis and suppresses invasion through the PI3K/Akt pathway in human breast cancer.
RY10-4, a novel protoapigenone analog, shows potent cytotoxicity against a broad spectrum of human cancer cells. Here we investigate its anti-tumor activity on breast cancer. The results indicated that RY10-4 suppressed proliferation, arrested cell cycle, induced apoptosis and inhibited invasion in MDA-MB-231, MCF-7 and SKBR3 breast cancer cells. Western blot analysis showed that RY10-4 down-regulated the PI3K/Akt signaling pathway and inhibited doxorubicin-induced p-Akt. Moreover, it effectively suppressed tumor growth in mice without major side effects. Therefore, RY10-4 had potential anti-tumor activity, and could be used as a lead to design more potent derivatives.
Key Laboratory of Natural Medicinal Chemistry and Resources Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Qianying
Q
Yuan
Shaoxin
S
Cai
Xuenong
X
Zhang
Ziwei
Z
Liu
Zhaoming
Z
Li
Xuelai
X
Luo
Chaomei
C
Xiong
Jianping
J
Wang
Junbo
J
Hu
Jinlan
J
Ruan
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011753:Pyrones / Q000494:pharmacology*; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
C574037:2-(1-hydroxy-4-oxocyclohexa-2,5-dienyl)pyran-4-one; D000970:Antineoplastic Agents; D011753:Pyrones; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt