Anti-cancer Effect of Luminacin, a Marine Microbial Extract, in Head and Neck Squamous Cell Carcinoma Progression via Autophagic Cell Death.
OBJECTIVE
The purpose of this study is to determine whether luminacin, a marine microbial extract from the Streptomyces species, has anti-tumor effects on head and neck squamous cell carcinoma (HNSCC) cell lines via autophagic cell death.


METHODS
Inhibition of cell survival and increased cell death was measured using cell viability, colony forming, and apoptosis assays. Migration and invasion abilities of head and cancer cells were evaluated using wound healing, scattering, and invasion assays. Changes in the signal pathway related to autophagic cell death were investigated. Drug toxicity of luminacin was examined in in vitro HaCaT cells and an in vivo zebrafish model.


RESULTS
Luminacin showed potent cytotoxicity in HNSCC cells in cell viability, colony forming, and fluorescence-activated cell sorting analysis. In vitro migration and invasion of HNSCC cells were attenuated by luminacin treatment. Combined with Beclin-1 and LC3B, Luminacin induced autophagic cell death in head and neck cancer cells. In addition, in a zebrafish model and human keratinocyte cell line used for toxicity testing, luminacin treatment with a cytotoxic concentration to HNSCC cells did not cause toxicity.


CONCLUSIONS
Taken together, these results demonstrate that luminacin induces the inhibition of growth and cancer progression via autophagic cell death in HNSCC cell lines, indicating a possible alternative chemotherapeutic approach for treatment of HNSCC.
Department of Otolaryngology, Ajou University School of Medicine, Suwon, Korea.
Yoo Seob
YS
Shin
Department of Otolaryngology, Ajou University School of Medicine, Suwon, Korea.
Hyun Young
HY
Cha
Department of Otolaryngology, Ajou University School of Medicine, Suwon, Korea.|Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon, Korea.
Bok-Soon
BS
Lee
Department of Otolaryngology, Ajou University School of Medicine, Suwon, Korea.|Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon, Korea.
Sung Un
SU
Kang
Department of Otolaryngology, Ajou University School of Medicine, Suwon, Korea.
Hye Sook
HS
Hwang
Natural Medicine Center, KIST Gangneung Institute, Gangneung, Korea.
Hak Cheol
HC
Kwon
Department of Otolaryngology, Ajou University School of Medicine, Suwon, Korea.|Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon, Korea.
Chul-Ho
CH
Kim
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.
Eun Chang
EC
Choi
D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001547:Benzaldehydes / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D002457:Cell Extracts / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018450:Disease Progression; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D013141:Spiro Compounds / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D015027:Zebrafish / Q000196:embryology
D001547:Benzaldehydes; D002457:Cell Extracts; D013141:Spiro Compounds; C413565:luminacin D
Autophagy; Cytotoxicity; Head and neck neoplasms; Luminacin; Streptomyces