As a kind of inorganic metal-oxide cluster compound, polyoxometalates' potential antitumor activities have gained much attention. In this paper, the bioactivities of a series of rare earth substituted phosphotungstic acids containing 5-fluorouracil, K₉(C₄H₄FN₂O₂)₂La(PW₁₁O₃₉)₂·18H₂O, K₉(C₄H₄FN₂O₂)₂Ce(PW₁₁O₃₉)₂·23H₂O, K₉(C₄H₄FN₂O₂)₂Nd(PW₁₁O₃₉)₂·25H₂O, K₉(C₄H₄FN₂O₂)₂Sm(PW₁₁O₃₉)₂·11H₂O and K₉H(C₄H₄FN₂O₂)Eu(PW₁₁O₃₉)₂·11H₂O (abbr. FLnPW, Ln=La, Ce, Nd, Sm, Eu) on HeLa cell are investigated. 5-fluorouracil (abbr. 5-FU) is used as positive control, and phosphotungstate containing 5-fluroracil K11C₄H₄FN₂O₂(PW₁₁O₃₉)·7H₂O (abbr. FPW) and phosphotungstic acid H₃PW₁₂O₄₀ (abbr. PW) are also tested. Morphological analysis shows that typical characteristics of apoptosis appear after treatment with the above compounds (besides PW), and nuclear chromatin is highly concentrated and marginalized. Flow cytometry indicates that S phase cell cycle arrest is induced by compounds (besides PW), whose FPW shows higher S-phase arrest activity than 5-FU, and that the FCePW, FNdPW and FEuPW groups show S phase and G₂/M phase arrests simultaneously. Flow cytometry also shows that all compounds except PW induce apoptosis in HeLa cells, and that the apoptosis-inducing activity order is FLnPW > FPW > 5-FU. Caspase 3 detection shows that caspase 3 activity of HeLa cell is enhanced after treatment with compounds, and the caspase 3 activity order is FLnPW>FPW>5-FU, where the FCePW and FEuPW groups show significant higher activities. These results show that the above compounds containing 5-FU group possess cell cycle arrest activity, apoptosis-inducing activity and caspase 3 inducing activity, while PW could only cause cell death because of acidity. It is suggested that 5-FU group and rare earth elements play most important roles in the antitumor activity, and FLnPW could inhibit cell proliferation by inducing cell cycle arrest, activating the caspase 3-dependent apoptosis pathway.

polyoxometalates  /  5-fluororacil  /  antitumor  /  apoptosis  /  cell cycle arrest