Diallylpolysulfides induce growth arrest and apoptosis.
Garlic-derived organo sulphur compounds such as diallylsulfides provide a significant protection against carcinogenesis. Chemically synthesized, and highly pure diallylsulfides with a chain of 1-4 sulphur atoms, as well as a range of control compounds, were employed to investigate the influence of these agents on cell viability, cell cycle arrest and induction of apoptosis in HCT116 human colon cancer cells. Diallyltrisulfide, and even more efficiently diallyltetrasulfide treatment of HCT116 cells led to a reduced cell viability, cell cycle arrest and apoptosis. A similar activity was found for the propyl-analogues, while mono- and disulfides were considerably less active. Initial calculations point toward the ability of tri- and tetrasulfides to form reactive oxygen species (ROS). Here, we found that the induction of apoptosis was indeed dependent on the redox-state of the cell, with anti-oxidants being able to prevent sulfide-induced apoptosis. Furthermore, using HCT116 cells which were either positive or negative for p53 revealed that p53 is clearly dispensable for induction of apoptosis. Growth arrest and induction of apoptosis is associated with a considerable reduction of the level of cdc25C. These results support the therapeutic potential of polysulfides and allow insight into the mechanisms based on the polysulfide biochemistry.
Busch
Corinna
C
Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, D-66424 Homburg, Germany.
Jacob
Claus
C
Anwar
Awais
A
Burkholz
Torsten
T
Aicha Ba
Lalla
L
Cerella
Claudia
C
Diederich
Marc
M
Brandt
Wolfgang
W
Wessjohann
Ludger
L
Montenarh
Mathias
M
D000498:Allyl Compounds / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry; D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002625:Chemistry, Organic / Q000379:methods; D005434:Flow Cytometry; D005737:Garlic; D006801:Humans; D013440:Sulfides / Q000737:chemistry; D013455:Sulfur / Q000737:chemistry; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000498:Allyl Compounds; D000975:Antioxidants; D013440:Sulfides; D016159:Tumor Suppressor Protein p53; D013455:Sulfur