Cervical cancer has been the fourth most common
cancer killing many women across the world.
Carnosic acid (CA), as a phenolic
diterpene, has been suggested to against
cancer, exerting protective effects associated with inflammatory
cytokines. It is aimed to demonstrate the therapeutic role of
carnosic acid against
cervical cancer and indicate its underlying molecular mechanisms. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium
bromide (MTT) was performed to assess the possible anti-proliferative effects of
carnosic acid. And also, colony formation was used to further estimate
carnosic acid's ability in suppressing
cervical cancer cells proliferation. Flow cytometry assays were performed here to indicate the alterations of
cervical cancer cells cycle and the development of apoptosis. Western blot assays and RT-PCR were also applied to clarify the apoptosis-associated signaling pathways affected by
reactive oxygen species (ROS) generation. And immunofluorescence was used to detect ROS-positive cells. In vivo experiments, CaSki xenograft model samples of nude mice were involved to further elucidate the effects of
carnosic acid. In our results, we found that
carnosic acid exerted anti-
tumor ability in vitro supported by up-regulation of apoptosis and ROS production in
cervical cancer cells. Also, acceleration of ROS led to the phospharylation of (
c-Jun N-terminal kinase (JNK) and its-related signals, as well as activation of Endoplasmic Reticulum (ER) stress, promoting the progression of apoptosis via stimulating Caspase3 expression. The development and growth of xenograft
tumors in nude mice were found to be inhibited by the administration of
carnosic acid for five weeks. And the suppressed role of
carnosic acid in proliferation of
cervical cancer cells and apoptosis of nude mice with
tumor tissues were observed in our study. Taken together, our data indicated that
carnosic acid resulted in apoptosis both in vitro and vivo experiments via promoting ROS and activating JNK signaling pathways in human
cervical cancer cells, which supplied a potential
therapy for the application of
carnosic acid in clinical treatment.