Protein kinase A activation by β‑Lapachone is associated with apoptotic cell death in NQO1‑overexpressing breast cancer cells.

Protein kinase A activation by β‑Lapachone is associated with apoptotic cell death in NQO1‑overexpressing breast cancer cells. Oncol Rep. 2019 Jul 19;: Authors: Zada S, Hwang JS, Ahmed M, Lai TH, Pham TM, Kim DH, Kim DR Abstract One million females are diagnosed worldwide every year with breast cancer, and the mortality rate of these patients remains high. Several treatments, including surgery, are available for breast cancer. β‑Lapachone (β‑Lap), a natural quinone compound, has been developed for cancer treatment due to its strong cytotoxic effect through its action on NAD(P)H:quinone oxidoreductase 1 (NQO1)‑dependent activity. However, the mechanism in regards to how β‑Lap induces cytotoxicity in breast cancer cells is still elusive. In the present study, we showed that β‑Lap induced apoptotic cell death via activation of protein kinase A (PKA) in NQO1‑overexpressing MDA‑MB‑231 human breast cancer cells. This PKA‑dependent cell death was observed solely in NQO1‑overexpressing 231 cells via the high production of reactive oxygen species (ROS). Cell survival of antioxidant [N‑acetylcysteine (NAC)]‑treated NQO1‑overexpressing 231 cells was significantly recovered, and NQO1‑negative 231 cells did not respond to β‑Lap. Antiapoptotic proteins such as Bcl2 and Bcl‑xL were decreased, while proapoptotic proteins, including cytochrome c, activation of caspase‑3, and cleavage of PAR...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

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