Cellular Mechanism Studies Of Two Monofunctional Platinum Complexes

Apoptosis, a common programmed cell death known by people, is the main way to inhibit the proliferation of cancer cells and kill cancer cells by platinum anticancer drugs and complexes. In fact, apart from apoptosis, there are several other kinds of cell death, such as autophagic cell death, paraptosis and necrosis, which can also inhibit cell proliferation. Up to now, only very few platinum complexes were reported to induce non-apoptotic cell death. Oxaliplatin induces cell death by mitotic catastrophe. JM335induce non-apoptotic cell death.In the first two parts of the study, we find the cellular mechanism induced by this novel platinum complex is extremely different from that of cisplatin, like causing no DNA terminal cut and no expression of Caspase3. Meanwhile, this novel platinum complex induces the large expression of autophagy marker, LC3-II. And we can detect the autophagic vacuoles. TEM also shows the large vesicle-like structures which seem to come from the swelling of mitochondria and endoplasmic reticulum. All of these results further verify that the platinum complex induces two non-apoptotic cell deaths, autophagic cell death and paraptosis.The last part of the study, we introduce the cellular mechanism of another3N chelated fluorescent monofunctional platinum complex. In the previous study, this complex also has the different cellular mechanism compared to cisplatin, which induces lots of vesicle-like structures, no expression of Caspase3, and no cell cycle arrest. However, no expression of LC3-II is found when treated with this complex. So we can draw the conclusion that the vacuoles in the cytoplasm are not autophagic vacuoles. Its further cellular mechanism is required to be studied.