Biological effects of copper, silver and gold camphorimine complexes in ovarian cancer cells

Surgical excision combined with chemotherapy with cisplatin derivatives is the main treatment of ovarian cancer. Although it is effective as first-line regime, 75% of the patients can experience recurrence, becoming vulnerable to develop resistance to chemotherapy.

The unique biological properties of camphorimine complexes based on metal sources such as CuCl, CuCl₂, Ag(NO₃), Ag(OAc) and KAu(CN)₂ anticipate their potential as alternative to cisplatin based therapies.

Some of us (MFNN Carvalho et al.) have been exploring the biological activity of silver camphorimine complexes against ovarian cancer cells (A2780/A2780cisR). The results revealed higher activity than cisplatin in cancer cells and low toxicity in non-tumoral cells HEK 293.

Encouraged by such results, we investigated biological effects of different metals on the properties of camphorimine complexes in order to evaluate their therapeutic value - studying their cytotoxic activity, cellular distribution, uptake and mechanism of action in OVCAR3 ovarian cancer cells. Due to the high spatial resolution in the micrometer range and high sensitivity for metal detection, nuclear microscopy techniques were used to image the metal distribution and evaluate the metal uptake in a whole cell. Data obtained indicate that the low cellular uptake of copper by OVCAR3 cells can explain the lower cytotoxicity of these complexes. Only [(CuCl)₂(OC₁₀H₁₄NC₆H₄NH₂)] caused a slight copper accumulation in the nuclear region. Results highlight the importance of characterizing the cellular uptake and distribution in cells to have clues on the cellular targets and understand complexes binding ability in cells.