Calcitriol exerts an anti-tumor effect in osteosarcoma by inducing the endoplasmic reticulum stress response.

ABSTRACT: Osteosarcoma is the most common type of primary bone tumor, and novel therapeutic approaches for this disease are urgently required. To identify effective agents, we screened a panel of Food and Drug Administration (FDA)-approved drugs in AXT cells, our newly established mouse osteosarcoma line, and identified calcitriol as a candidate compound with therapeutic efficacy for this disease. Calcitriol inhibited cell proliferation in AXT cells by blocking cell cycle progression. From a mechanistic standpoint, calcitriol induced endoplasmic reticulum (ER) stress, which was potentially responsible for downregulation of cyclin D1, activation of p38 MAPK, and intracellular production of reactive oxygen species (ROS). Knockdown of Atf4 or Ddit3 restored cell viability after calcitriol treatment, in

SUBMITTER: Shimizu T 

PROVIDER: S-EPMC5581526 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature