Hemiprotonic ph-ph+ with two targets inhibits metastatic breast cancer and concurrent candidiasis.

ABSTRACT

Concurrent infection in breast cancer patients is the direct cause of the high mortality rate of the disease. However, there is no available method to increase the survival rate until now. To address the problem, we propose one drug with two target strategy to treat the refractory disease. A small chemical, ph-ph+, was attempted to be used in the study to explore the feasibility of the approach in anticancer and antifungus at the same time. The results showed that ph-ph+ could prevent the proliferation and metastasis of breast cancer cells, and kill C. albicans simultaneously. The molecular mechanism was associated with the activation of an evolutionarily conserved protease CLpP in the cancer and C. albicans cells. Also, the signaling pathway mediated by PLAGL2 that highly expressed in cancer cells participated in preventing cell metastasis and inducing apoptosis of ph-ph+. The one drug with dual targets inhibited the growth and metastasis of the cancer cells, and meanwhile eliminated C. albicans in tissues in the experimental animals. The results suggested that ph-ph+ with dual targets of CLpP and PLAGL2 would be a feasible approach to prolong the survival rate in patients with metastatic breast cancer and pathogenic infection.