Sporoderm-Broken Spores of Ganoderma lucidum Inhibit the Growth of Lung Cancer: Involvement of the Akt/mTOR Signaling Pathway.
The sporoderm-broken spores of Ganoderma lucidum (SBGS) and their extracts exhibited a wide range of biological activities. In the present study, we prepare ethanol/ethanol extract (E/E-SBGS) and ethanol/aqueous extract (E/A-SBGS) from SBGS and examine their antitumor activities against human lung cancer. Our results showed that E/E-SBGS, not E/A-SBGS, inhibited the survival and migration of lung cancer cells in a dose-dependent manner. E/E-SBGS arrested cell cycle at G2/M phase and triggered apoptosis by decreasing the expression and activity of cell cycle regulators, cyclin B1 and cdc2, as well as anti-apoptotic proteins, Bcl-2 and Bcl-xl. Consequently, colony formation of lung cancer cells was markedly blocked by E/E-SBGS at subtoxic concentrations. Oral administration of both E/E-SBGS and SBGS significantly suppressed tumor volume and tumor weight without gross toxicity in mice. Mechanism study showed that E/E-SBGS dose-dependently suppressed the activation of Akt, the mammalian target of rapamycin (mTOR) and their downstream molecules S6 kinase and 4E-BP1 in treated tumor cells. Taken together, these results indicate that the ethanol extract of sporoderm-broken spores of G. lucidum suppresses the growth of human lung cancer, at least in part, through inhibition of the Akt/mTOR signaling pathway, suggesting its potential role in cancer treatments.
a Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China; Pediatric Translational Medicine Institute, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University , Shanghai , China.
Yali
Y
Chen
b Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai , China.
Jing
J
Lv
c National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Medical University , Nanning , China.
Kun
K
Li
d Zhejiang Rare Herb Medicine Engineering Research Center , Jinhua , Zhejiang , China.
Jing
J
Xu
e Shouxiangu Pharmaceutical Company Limited , Jinhua , Zhejiang , China.
Mingyan
M
Li
f Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai , China.
Wen
W
Zhang
f Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University , Shanghai , China.
Xiufeng
X
Pang
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D016195:G2 Phase / Q000187:drug effects; D032902:Ganoderma / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013172:Spores, Fungal / Q000737:chemistry* / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D009363:Neoplasm Proteins; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases