Mor-platin a new platinum complex that can induce apoptosis and inhibit migration

Abstract

Since cisplatin was discovered and applied clinically, people have synthesized thousands of platinum compound derivatives. These platinum derivatives are effective in chemotherapy for some tumors including testicular cancer, ovarian cancer, lung cancer, bladder cancer, head and neck cancer. All of these platinum complex are believed to exert their unparalleled anticancer potency by interacting with nulear DNA, resulting in DNA adducts formation and consequently lead to cell apoptosis, cell cycle arrest and reactive oxygen species released. However, these platinum complex are severely limited by drug resistance and undesirable side effects arising from relatively low specificity and resultant high dosage requirement. To overcome the drug-resistance and improve therapeutic efficiency, it is necessary to synthesized new platinum complex. Our group successfully synthesized a new platinum complex Mor-platin, it can significantly damage more tumor cells than traditional drug cisplatin, while the other biological effects have not been studied. This work aims to study the effect of Mor-platin on its anti-cancer ability, cell migration and cell invasion. In order to detect anti-cancer efficiency, MTT assay was used, and the results showed that IC50 of Mor-platin (14.41 μ g mL - 1) was far less than IC50 of cisplatin (97.29 μ g mL - 1), suggesting that Mor-platin have potentially higher tumor cytotoxicity than cisplatin. Next, we used reactive oxygen species assay kit, western blot analysis, apoptosis and cell cycle kit to assess whether Mor-platin can cause cell death by apoptosis, cell cycle, ROS, apoptosis-related protein and caspase protein. The results showed that Mor-platin can increase level of ROS, arrest cell cyle in S phase, increase ratio of Bax/Bcl-2 and activate caspase 3/8/9 resulting in cleaved PARP, ultimately lead to cell death. The major threat of cancer is not from the primary tumor itself but from metastasis to other organs. To develop successful metastases, cancer cells need to disseminate to a distant organ, migrate out of the primary tumor, invade to blood or lymphatic vessels, finally seed, proliferate and colonize to form secondary tumors. Cell migration is a basic process within the cancer. Tumor metastasis is a major cause of cancer deaths, 90% of the cancer deaths can be attributed to the tumor metastasis, therefore it is necessary to avoid tumor metastasis on clinical cancer treatment. Only understanding the clear tumor metastasis for emerging antitumor drugs, they can be obtained to development and application. Current tumor metastasis experiments include transwell assay, wound-healing assay, microcarrier beads, three-dimensional assay and so on. Here, we used wound-healing assay and transwell assay to quantify the migration inhibitory activity of Mor-platin. Intriguingly, both wound-healing assay and transwell assay showed that Mor-platin can also inhibit cell migration and invasion, while cisplatin did not show any same effects. In summary, this new platinum complex Mor-platin not only have high anti-cancer efficiency but also inhibit migration, providing a novel strategy for the development of next generation platinum complex with optimal anti-tumor activities.