OPEN IN READ APP
JOURNAL ARTICLE

Diallyl trisulfide suppresses the proliferation and induces apoptosis of human colon cancer cells through oxidative modification of beta-tubulin

Takashi Hosono, Tomomi Fukao, Jun Ogihara, Yoshimasa Ito, Hajime Shiba, Taiichiro Seki, Toyohiko Ariga
Journal of Biological Chemistry 2005 December 16, 280 (50): 41487-93
16219763
Allyl sulfides are characteristic flavor components obtained from garlic. These sulfides are thought to be responsible for their epidemiologically proven anticancer effect on garlic eaters. This study was aimed at clarifying the molecular basis of this anticancer effect of garlic by using human colon cancer cell lines HCT-15 and DLD-1. The growth of the cells was significantly suppressed by diallyl trisulfide (DATS, HCT-15 IC50 = 11.5 microM, DLD-1 IC50 = 13.3 microM); however, neither diallyl monosulfide nor diallyl disulfide showed such an effect. The proportion of HCT-15 and that of DLD-1 cells residing at the G1 and S phases were decreased by DATS, and their populations at the G2/M phase were markedly increased for up to 12 h. The cells with a sub-G1 DNA content were increased thereafter. Caspase-3 activity was also dramatically increased by DATS. Fluorescence-activated cell sorter analysis performed on the cells arrested at the G1/S boundary revealed cell cycle-dependent induction of apoptosis through the transition of the G2/M phase to the G1 phase by DATS. DATS inhibited tubulin polymerization in an in vitro cell-free system. DATS disrupted microtubule network formation of the cells, and microtubule fragments could be seen at the interphase. Peptide mass mapping by liquid chromatography-tandem mass spectrometry analysis for DATS-treated tubulin demonstrated that there was a specific oxidative modification of cysteine residues Cys-12beta and Cys-354beta to form S-allylmercaptocysteine with a peptide mass increase of 72.1 Da. The potent antitumor activity of DATS was also demonstrated in nude mice bearing HCT-15 xenografts. This is the first paper describing intracellular target molecules directly modified by garlic components.

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
16219763
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"