Morus alba Accumulates Reactive Oxygen Species to Initiate Apoptosis via FOXO-Caspase 3-Dependent Pathway in Neuroblastoma Cells.
Morus alba root extract (MARE) has been used to treat hyperglycaemic conditions in oriental medicine. Here, we studied whether MARE possesses a cytotoxic effect on neuroblastoma. To check the cytotoxicity generated by MARE was whether relatively higher against the cancer cells rather than normal cells, we chose a neuroblastoma cell line (B103) and a normal cell line (Rat-2). A CCK assay revealed that MARE (10 μg/ml) reduced cell viability to approximately 60% compared to an untreated control in B103 cells. But in Rat-2 cells, MARE induced relatively lower cytotoxicity. To investigate the mechanisms underlying the cytotoxic effect of MARE, we used flow cytometry combined with immunoblot analyses. We found that MARE-treatment could accumulate ROS and depolarize mitochondria membrane potential of B103 cells. Further treatment with MARE in B103 cells also could damage DNA and induce apoptosis. An expression study of p-Akt also suggested that there was a reduction in cellular proliferation and transcription along with the process of apoptosis, which was further evidenced by an increase in Bax and cleaved-caspase 3 activity. Together, our findings suggest that MARE produces more cytotoxicity in cancer cells while having a relatively attenuated effect on normal cells. As such, MARE may be a safer option in cancer therapeutics, and it also shows potential for the patients with symptoms of hyperglycemia and cancer.
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, College of Natural Science, Hallym University, Chuncheon 200-702, Korea.
Young Hwi
YH
Kwon
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, College of Natural Science, Hallym University, Chuncheon 200-702, Korea.
Kausik
K
Bishayee
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, College of Natural Science, Hallym University, Chuncheon 200-702, Korea.
Ataur
A
Rahman
Department of Physical Education, College of Natural Science, Hallym University, Chuncheon 200-702, Korea.
Jae Seung
JS
Hong
Department of Food Science and Nutrition, College of Natural Science, Hallym University, Chuncheon 200-702, Korea.
Soon-Sung
SS
Lim
Department of Pharmacology, College of Medicine, Institute of Natural Medicine, College of Natural Science, Hallym University, Chuncheon 200-702, Korea.
Sung-Oh
SO
Huh
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D031625:Morus / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D051381:Rats; D017382:Reactive Oxygen Species / Q000494:pharmacology; D015398:Signal Transduction; D000071161:Forkhead Box Protein O1
D053148:Caspase 3; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1
cytotoxicity; intrinsic cell death pathway; neuroblastoma; proliferation; reactive oxygen species