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BMC Complement Altern Med. 2017 Feb 1;17(1):88. doi: 10.1186/s12906-017-1611-9.

Chlorella sorokiniana induces mitochondrial-mediated apoptosis in human non-small cell lung cancer cells and inhibits xenograft tumor growth in vivo.

Lin PY1,2, Tsai CT3, Chuang WL1, Chao YH4, Pan IH5, Chen YK6, Lin CC7,8,9, Wang BY10,11,12,13.

Author information

1
Transplant Medicine & Surgery Research Centre, Changhua Christian Hospital, Changhua, Taiwan.
2
Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
3
Department of Public Health, School of Public Health, China Medical University, Taichung, Taiwan.
4
Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan.
5
Biomedical Technology and Device Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
6
Department of Food Science, National Pingtung University of Science and Technology, Pingtung, Taiwan.
7
Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. lincc@dragon.nchu.edu.tw.
8
Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan. lincc@dragon.nchu.edu.tw.
9
Department of Biotechnology, Asia University, Taichung, Taiwan. lincc@dragon.nchu.edu.tw.
10
Division of Thoracic Surgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan. 156283@cch.org.tw.
11
School of Medicine, Chung Shan Medical University, Taichung, Taiwan. 156283@cch.org.tw.
12
School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 156283@cch.org.tw.
13
Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan. 156283@cch.org.tw.

Abstract

BACKGROUND:

Lung cancer is one of the leading causes of cancer related deaths worldwide. Marine microalgae are a source of biologically active compounds and are widely consumed as a nutritional supplement in East Asian countries. It has been reported that Chlorella or Chlorella extracts have various beneficial pharmacological compounds that modulate immune responses; however, no studies have investigated the anti-cancer effects of Chlorella sorokiniana (CS) on non-small cell lung cancer (NSCLC).

METHODS:

In this study, we evaluated the anti-cancer effects of CS in two human NSCLC cell lines (A549 and CL1-5 human lung adenocarcinoma cells), and its effects on tumor growth in a subcutaneous xenograft tumor model. We also investigated the possible molecular mechanisms governing the pharmacological function of CS.

RESULTS:

Our results showed that exposure of the two cell lines to CS resulted in a concentration-dependent reduction in cell viability. In addition, the percentage of apoptotic cells increased in a dose-dependent manner, suggesting that CS might induce apoptosis in human NSCLC cells. Western blot analysis revealed that exposure to CS resulted in increased protein expression of the cleaved/activated forms of caspase-3, caspase-9, and PARP, except caspase-8. ZDEVD (caspase-3 inhibitor) and Z-LEHD (caspase-9 inhibitor) were sufficient at preventing apoptosis in both A549 and CL1-5 cells, proving that CS induced cell death via the mitochondria-mediated apoptotic pathway. Exposure of A549 and CL1-5 cells to CS for 24 h resulted in decreased expression of Bcl-2 protein and increased expression of Bax protein as well as decreased expression of two IAP family proteins, survivin and XIAP.

CONCLUSIONS:

We demonstrated that CS induces mitochondrial-mediated apoptosis in NSCLC cells via downregulation of Bcl-2, XIAP and survivin. In addition, we also found that the tumors growth of subcutaneous xenograft in vivo was markedly inhibited after oral intake of CS.

KEYWORDS:

Chlorella sorokiniana; Human non-small cell lung cancer cells; Mitochondrial apoptotic pathway

PMID:
28143460
PMCID:
PMC5286777
DOI:
10.1186/s12906-017-1611-9
[Indexed for MEDLINE]
Free PMC Article

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