Novel effect and the mechanistic insights of fruiting body extract of medicinal fungus Antrodia cinnamomea against T47D breast cancer.
BACKGROUND
Tamoxifen, an anti-oestrogenic drug for estrogen receptor positive (ER+) breast cancer, was observed to stimulate tumor growth or drug resistance in patients. Antrodia cinnamomea (AC), a precious medicinal fungus has been traditionally used as a folk remedy for cancers in Asian countries. The objective of this study was to investigate the bioefficacy and the underlying molecular mechanisms of the AC fruiting bodies extracts (AC-3E) against human ER+ T47D breast cancer cells, and compare the effect with that of tamoxifen.


METHODS
Cell proliferation, migration, TUNEL assay, western blotting, time-lapse confocal microscopy analyses, chorioallantoic membrane assay, and a xenograft BALB/c nude mouse system were used in this study. Chemical fingerprinting of AC-3E was established using LC-MS.


RESULTS
AC-3E attenuated T47D breast cancer cell activity by deregulating the PI3K/Akt/mTOR signaling pathway and key cell-cycle mediators, and inducing apoptosis. AC-3E also effectively inhibited tube-like structures of endothelial cells, blood vessel branching and microvessel formation ex vivo and in vivo. Significant preventive and therapeutic effects against T47D mammary tumor growth of AC-3E was observed comparable or superior to tamoxifen treatment in xenograft BALB/c nude mice. Dehydroeburicoic acid (2) was characterized as the main chemical constituent in AC-3E against breast cancer.


CONCLUSIONS
This study suggests that AC-3E extracts can be employed as a double-barreled approach to treat human ER+ breast cancer by attacking both cancer cells and tumor-associated blood vessel cells.
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
Kuang-Ming
KM
Shang
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
Tzu-Hsuan
TH
Su
School of Science, Monash University Sunway Campus, Selangor, Malaysia.
Wai Leng
WL
Lee
Experimental Forest, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan.
Wen-Wei
WW
Hsiao
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
Ching-Yi
CY
Chiou
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
Bing-Ying
BY
Ho
Department of Forestry, National Chung Hsing University, Taichung, Taiwan.
Sheng-Yang
SY
Wang
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan; PhD Program in Translational Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan. Electronic address: lfshyur@ccvax.sinica.edu.tw.
Lie-Fen
LF
Shyur
D000818:Animals; D055491:Antrodia / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D048690:Fruiting Bodies, Fungal / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
D010936:Plant Extracts; D019869:Phosphatidylinositol 3-Kinases
Anti-angiogenesis; Antrodia cinnamomea; Dehydroeburicoic acid; ER+ T47D breast cancer; Tamoxifen