Compound SLXM-2, a derivative of cyclophosphamide （CTX）, has shown potent growth-inhibitory effect on tumor cells with low toxicity in previous studies. However, the mechanism of its anti-tumor effect, especially on DNA damage, remains largely unclear. This study investigated the effect of SLXM-2 on the survival time of mice transplanted with the ascitie fluid-type hepatocarcinoma 22 （H22）. We also evaluated the correlation between DNA damaging effect of SLXM-2 and its anti-tumor effect, and to probe the possible molecular mechanism for its effect on H22 cells. The results suggested that SLXM-2 significantly （P〈0.05） prolonged the survival time of mice bearing the ascitic fluid-type H22. Furthermore, SLXM-2 induced DNA damage in a dose-dependent manner in H22 cells. Further investigation revealed that SLXM-2 significantly （P〈0.05） up-regulated the expression levels of a series of DNA damage-related proteins, such as γH2AX （Ser139）, p-Chkl （Ser296）, p-Chk2 （Thr68）, p-p53 （Ser15）, p-p53 （Ser20） and p21, and down-regulated the expression of p-ATR （Ser428） and p-ATM （Ser1981）. In conclusion, SLXM-2 showed a remarkable anti-tumor activity on ascitic fluid-type H22 cells, and its molecular mechanism is related to its DNA damaging effect.
Compound YSY-01A, a recently synthesized proteasome inhibitor, has shown potent growth-inhibitory effect on tumor cells in previous researches. However, the mechanism of its inhibitory effects, especially on cell cycle, remains largely unclear. This study aimed to evaluate the correlation between cell cycle arrest effect of YSY-01A and its anti-cancer effect, and to probe the possible molecular mechanisms for its effects on human ovarian cancer SK-OV-3 cells. The results suggested that YSY-01A significantly （P〈0.05） inhibited cellular proliferation of SK-OV-3 cells in a concentration-dependent and time-dependent manner. Furthermore, YSY-01A induced a G2/M cell cycle arrest of SK-OV-3 cells. Further investigation revealed that YSY-01A significantly （P〈0.05） changed the expression levels of a series of cell cycle related protein, such as cyclin B1, cdc2, and p-cdc2 （T14）. Meanwhile, YSY-01A could inhibit the TNF-a-induced NF-kB nuclear translocation and lead to the increase of 1kBa as well as the decrease of IKK and Gadd45a In conclusion, YSY-01A showed remarkable anti-cancer activity on SK-OV-3 cells, and its molecular mechanisms were related to G2/M cell cycle arrest.
Compound 209 is a newly synthesized dithiocarbamate derivative with antiproliferation activity in vitro, however, its antitumor effect in vivo and the underlying mechanisms have yet to be identified. We explored the antitumor effect of compound 209 and the possible mechanisms for its inhibition of the growth of HT-29 xenograff tumor and proliferation of HT-29 cells. Cell proliferation was evaluated with SRB assay in vitro. The results showed that compound 209 had significant antiproliferation activity on HT-29 cells. Furthermore, the xenograff HT-29 nude mouse model was used to study the antitumor effect of compound 209 in vivo. We found that compound 209 significantly inhibited tumor growth and did not cause loss of body weight or leukocytopenia. Analysis by flow cytometry indicated that compound 209 arrested HT-29 cell cycle in G~ phase. Western blotting analysis suggested that compound 209 increased the expression of p27, cyclin E, CDK2, cyclin D1 and CDK4. These results demonstrated the antitumor effect of compound 209 and its potential use as an anticancer drug.
