Bis(phenylidenebenzeneamine)-1-disulfide Derivatives Induce Autophagy in Melanoma Cells Through a Mitochondria-mediated Pathway.
We have previously reported the efficient synthesis of bis(phenylidenebenzeneamine)-1-disulfide derivatives 1-8. In the present article, we delineated the signaling pathways involved in the anticancer effects of compound 2 on melanoma cells. The treatment of melanoma cells with compound 2 resulted in ROS generation, a decrease in ΔΨmt, ATP, and protein expression of mitochondrial respiratory chain subunits. In addition, no significant apoptotic or necrotic effect was seen following compound 2 treatment using an annexin V and propidium iodide (PI) double-staining. Nevertheless, autophagy-related proteins LC3 and Beclin 1 were enhanced by compound 2. Furthermore, compound 2 was also shown to reduce murine melanoma size in a mouse model. We revealed a novel bio-evaluation of bis(phenylidenebenzeneamine)-1-disulfide derivatives anti-tumor proliferation mechanism and suggest that these agents may have potential chemotherapeutic activity for melanoma cells.
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan, R.O.C. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan, R.O.C.
Wan-Ping
WP
Hu
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan, R.O.C.
Chia-Chen
CC
Hsu
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Kaohsiung, Taiwan, R.O.C.
Ya-Ching
YC
Wang
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.
Gopal Chandru
GC
Senadi
Department of Surgery, School of Medicine, Kaohsiung Medical University, Taiwan, R.O.C.
Kung-Kai
KK
Kuo
Department of Chemistry, National Chung Hsing University, Taichung, Taiwan, R.O.C.
Jen-Fon
JF
Jen
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C. jjwang@kmu.edu.tw.
Jeh-Jeng
JJ
Wang
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D004220:Disulfides / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D004220:Disulfides; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate
autophagy; bis(phenylidenebenzeneamine)-1-disulfide; melanoma; mitochondria