Growth inhibitory effect of paratocarpin E, a prenylated chalcone isolated from Euphorbia humifusa Wild., by induction of autophagy and apoptosis in human breast cancer cells.
Five flavones, including four flavonoids and one prenylated chalcone (paratocarpin E), were isolated from E. humifusa. and their chemical structures were established by spectroscopic analyses. We assessed the efficacy of these compounds against the growth of human breast cancer, leukemic, kidney cancer cell lines. Among them, paratocarpin E showed significant cytotoxicity against these cancer cell lines with an IC50of 19.6μM on the growth of MCF-7 cells. Paratocarpin E treatment of MCF-7 cells resulted in typical apoptotic features via increasing expression of activated caspase-8 and -9 and PARP cleavage. Moreover, paratocarpin E altered the expression of Bax and Bcl-2, leading to the release of cytochrome c from the mitochondria into the cytosol, suggesting that the mitochondria-mediated apoptosis was initiated. In addition, paratocarpin E increased the MDC-positive autophagic vacuoles, the ratio of LC3-II/LC3-I protein levels of Beclin-1, but decreased p62 expression, indicating the potent pro-autophagic effects of paratocarpin E in MCF-7 cells. Mechanistically, cell death induced by paratocarpin E is able to induce apoptosis of MCF-7 cells by activating p38 and JNK signaling pathway while inhibiting Erk pathway. Furthermore, paratocarpin E promotes the activation and nuclear translocation of NF-κB, which plays an important role in balancing paratocarpin E-mediated apoptosis and autophagy. The molecular docking study also revealed that paratocarpin E bound to Fas and NF-κB complex. These findings provide initial evidences that paratocarpin E can be used as a potential anti-cancer drug in future for breast cancer therapy.
Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Suyu
S
Gao
Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Dejuan
D
Sun
Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Guan
G
Wang
Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Jin
J
Zhang
Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Yingnan
Y
Jiang
School of Pharmacy, Shihezi University, Shihezi 832023, People's Republic of China.
Guoyu
G
Li
School of Pharmacy, Shihezi University, Shihezi 832023, People's Republic of China.
Ke
K
Zhang
Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Lei
L
Wang
Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Jian
J
Huang
Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: syzyclx@163.com.
Lixia
L
Chen
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D028481:Euphorbia / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D047188:Chalcones; C000620935:paratocarpin E
Apoptosis; Autophagy; Breast cancer; Euphorbia humifusa Wild.; Paratocarpin E