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Vanadium complexes inhibit growth of HT‐29 cells via ROS generation
Author(s) -
Moretti Brandon,
McCaffrey Vanessa,
Rabquer Bradley James
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.747.6
Subject(s) - cell growth , apoptosis , chemistry , growth inhibition , reactive oxygen species , cell culture , cancer cell , vanadium , cisplatin , intracellular , cell cycle , programmed cell death , cancer research , in vitro , cancer , microbiology and biotechnology , biochemistry , biology , medicine , chemotherapy , inorganic chemistry , genetics
Purpose Cancer is characterized by uncontrolled cell proliferation caused by a loss of control of cell cycle growth and division. Many chemotherapeutics have been developed to induce apoptosis or inhibit cancer cell growth. Previous studies have evidenced the efficacy of organometallic compounds, notably cisplatin and its derivatives, in inhibiting tumor growth. Further studies have been conducted with other metal elements to assess their potential as anti‐cancer drugs. One in particular is vanadium, which has been shown to elicit effects via multiple biochemical pathways. We previously synthesized novel vanadium complexes with variable functional groups and found that they were able to inhibit growth in breast (MCF‐7) and colon (HT‐29) cancer cell lines to varying degrees. Here, we hypothesized that these complexes were inducing apoptosis via caspase 3/7‐mediated pathways and inducing cell death by an increase in reactive oxygen species generation. Methods & Results HT‐29 cells were used as a model of colon cancer, along with a line of HEK293 cells, which served as a noncancerous model. Previously synthesized vanadium complexes (VCs) with 5‐Br and 3‐OMe functional groups were used as treatments in vitro . A cell proliferation assay was used to assess HEK293 growth inhibition after treatment with each VC. Results showed 55.2% (p<0.05) and 24.6% (p<0.05) growth inhibition for 0.5mM 5‐Br and 3‐OMe VCs, respectively, which is comparable to previously presented results with the HT‐29 cells. An intracellular ROS generation assay was used with both HT‐29 and HEK293 cell lines after being treated with 0.25 mM 5‐Br and 3‐OMe VCs for 4, 24, 48, and 72‐hour incubation periods. For the HT‐29 cells, there were no significant increases in ROS generation after 4, 24, or 48‐hour incubation periods with either treatment. After 72 hours, however, the 5‐Br‐VO 2 yielded a 51.3% (p<0.05) increase in intracellular ROS generation compared to the ligand control, and the 3‐OMe‐VO 2 yielded a 46.0% (p<0.05) increase. For the HEK293 cells, there was likewise no significant increase in ROS generation after 4‐hour incubation periods, but there was a 44.1% (p<0.05) increase in ROS generation after 24‐hour incubation with the 5‐Br‐VO 2 alone. There were no significant increases in ROS generation after the 24‐hour incubation period in the HEK293 cells. Finally, a caspase 3/7 apoptosis detection assay was also used to determine caspase pathway activation. Compared to the cisplatin positive control, the 5‐Br‐VO 2 treatment yielded no measurable caspase activation in the HT‐29 cells after 16 and 24 hours of incubation. Conclusion We found that VCs were able to effectively inhibit HT‐29 growth through likely intracellular generation of ROS, rather than through caspase activation of apoptosis. Support or Funding Information Hewlett‐Mellon Fund for Faculty Development at Albion College