PMID- 31586690 OWN - NLM STAT- MEDLINE DCOM- 20200323 LR - 20200323 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 247 DP - 2020 Jan 30 TI - Ganoderma lucidum spore oil induces apoptosis of breast cancer cells in vitro and in vivo by activating caspase-3 and caspase-9. PG - 112256 LID - S0378-8741(19)32056-2 [pii] LID - 10.1016/j.jep.2019.112256 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: The mushroom Ganoderma lucidum (G. lucidum) is a traditional Chinese medicine reported to have a variety of pharmacological properties, including anti-cancer activity. G. lucidum spore oil (GLSO) is a lipid substance extracted from sporoderm-broken spore of G. lucidum. However, the effect of GLSO on breast cancer and the underlying molecular mechanism remain unclear. AIM OF THE STUDY: The aim of this study was to identify the effects of GLSO on breast cancer cells in vitro and in vivo as well as to investigate the mechanistic basis for the anticancer effect of GLSO. MATERIALS AND METHODS: First, in vitro MDA-MB-231 cells were treated with GLSO (0.2, 0.4, and 0.6 muL/mL). The protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), X-linked inhibitor of apoptosis (XIAP), total poly (ADP-ribose) polymerase (PARP), caspase-3 and caspase-8 were examined using western blotting. The mRNA expression levels of Fas-associated protein with death domain (FADD), TNF receptor-associated factor 2 (TRAF2), caspases-3, -8, -9 and Bax were examined using qRT-PCR. Second, in vivo the anticancer properties of GLSO were assessed by H&E, TUNEL and immunohistochemistry in BALB/c mice injected with 4T1 cells. In addition, the levels of caspase-9/caspase-3 signaling pathway proteins in tumor tissue were evaluated by immunoblotting. Finally, MDA-MB-231 cells were treated with caspase inhibitors to measure cell viability, the protein levels were examined with western blotting. RESULTS: The results in vitro showed that GLSO up-regulated the expression of Bax and caspase-3 in MDA-MB-231 cells, but had no effect on the expression of caspase-8. Moreover, the growth of tumors in vivo was significantly suppressed in the GLSO-treated group. The results of Western blot were consistent with in vitro. In vitro, co-treatment of MDA-MB-231 cells with caspase inhibitors reduced the inhibitory effect of GLSO on cell growth. CONCLUSIONS: GLSO inhibits the growth of MDA-MB-231 cells and tumors in vivo by inducing apoptosis, which may be achieved through the mitochondrial apoptotic pathway. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Jiao, Chunwei AU - Jiao C AD - Guangdong Yuewei Edible Fungi Technology Co., Ltd., Guangzhou, 510663, PR China; State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, PR China. FAU - Chen, Wang AU - Chen W AD - Guangdong Yuewei Edible Fungi Technology Co., Ltd., Guangzhou, 510663, PR China. FAU - Tan, Xupeng AU - Tan X AD - Guangdong Yuewei Edible Fungi Technology Co., Ltd., Guangzhou, 510663, PR China. FAU - Liang, Huijia AU - Liang H AD - Guangdong Yuewei Edible Fungi Technology Co., Ltd., Guangzhou, 510663, PR China. FAU - Li, Jieyi AU - Li J AD - Guangdong Yuewei Edible Fungi Technology Co., Ltd., Guangzhou, 510663, PR China. FAU - Yun, Hao AU - Yun H AD - Guangdong Yuewei Edible Fungi Technology Co., Ltd., Guangzhou, 510663, PR China. FAU - He, Chunyan AU - He C AD - Guangdong Yuewei Edible Fungi Technology Co., Ltd., Guangzhou, 510663, PR China. FAU - Chen, Jiaming AU - Chen J AD - Guangdong Yuewei Edible Fungi Technology Co., Ltd., Guangzhou, 510663, PR China. FAU - Ma, Xiaowei AU - Ma X AD - Guangdong Yuewei Edible Fungi Technology Co., Ltd., Guangzhou, 510663, PR China. FAU - Xie, Yizhen AU - Xie Y AD - Guangdong Yuewei Edible Fungi Technology Co., Ltd., Guangzhou, 510663, PR China; State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, PR China. Electronic address: xyzgdim@sina.com. FAU - Yang, Burton B AU - Yang BB AD - Sunnybrook Research Institute, Toronto, M4N 3M5, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M5S 1A8, Canada. Electronic address: byang@sri.utoronto.ca. LA - eng PT - Journal Article DEP - 20191003 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Oils) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspase 9) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Breast Neoplasms/*drug therapy/pathology MH - Caspase 3/metabolism MH - Caspase 9/metabolism MH - Cell Line, Tumor/transplantation MH - Cell Proliferation/drug effects MH - Disease Models, Animal MH - Female MH - Humans MH - Medicine, Chinese Traditional/*methods MH - Mice MH - Oils/*pharmacology/therapeutic use MH - Reishi/*chemistry MH - Spores, Fungal/chemistry OTO - NOTNLM OT - Apoptosis OT - Breast cancer OT - Caspase-3 OT - Caspase-9 OT - Ganoderma lucidum OT - Sporoderm-broken spore oil EDAT- 2019/10/07 06:00 MHDA- 2020/03/24 06:00 CRDT- 2019/10/07 06:00 PHST- 2019/05/24 00:00 [received] PHST- 2019/09/25 00:00 [revised] PHST- 2019/09/25 00:00 [accepted] PHST- 2019/10/07 06:00 [pubmed] PHST- 2020/03/24 06:00 [medline] PHST- 2019/10/07 06:00 [entrez] AID - S0378-8741(19)32056-2 [pii] AID - 10.1016/j.jep.2019.112256 [doi] PST - ppublish SO - J Ethnopharmacol. 2020 Jan 30;247:112256. doi: 10.1016/j.jep.2019.112256. Epub 2019 Oct 3.