Grifolin inhibits tumor cells adhesion and migration via suppressing interplay between PGC1α and Fra-1/LSF-MMP2/CD44 axes
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Xiangjian Luo1,2,3, Namei Li1,2,3, Juanfang Zhong1,2,3, Zheqiong Tan1,2,3, Ying Liu4, Xin Dong1,2,3, Can Cheng1,2,3, Zhijie Xu1,2,3, Hongde Li1,2,3, Lifang Yang1,2,3, Min Tang1,2,3, Xinxian Weng1,2,3, Wei Yi1,2,3, Jikai Liu5, Ya Cao1,2,3
1Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China
2Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China
3Key Laboratory of Carcinogenesis, Chinese Ministry of Health, Changsha, Hunan 410078, China
4Department of Medicine, Hunan Traditional Chinese Medical College, Zhuzhou, Hunan 412000, China
5School of Pharmacy, South-Central University For Nationalities, Wuhan, Hubei 430074, China
Xiangjian Luo, email: [email protected]
Jikai Liu, email: [email protected]
Ya Cao, email: [email protected]
Keywords: grifolin, PGC1α, ROS, adhesion, migration
Received: April 13, 2016 Accepted: August 29, 2016 Published: September 10, 2016
Grifolin, a farnesyl phenolic compound isolated from the fresh fruiting bodies of the mushroom Albatrellus confluens, exhibits effective antitumor bioactivity in previous study of our group and other lab. In this study, we observed that grifolin inhibited tumor cells adhesion and migration. Moreover, grifolin reduced reactive oxygen species (ROS) production and caused cellular ATP depletion in high-metastatic tumor cells. PGC1α (Peroxisome proliferator-activated receptor γ, coactivator 1α) encodes a transcriptional co-activator involved in mitochondrial biogenesis and respiration and play a critical role in the maintenance of energy homeostasis. Interestingly, grifolin suppressed the mRNA as well as protein level of PGC1α. We further identified that MMP2 and CD44 expressions were PGC1α inducible. PGC1α can bind with metastatic-associated transcription factors: Fra-1 and LSF and the protein-protein interaction was attenuated by grifolin treatment. Overall, these findings suggest that grifolin decreased ROS generation and intracellular ATP to suppress tumor cell adhesion/migration via impeding the interplay between PGC1α and Fra-1 /LSF-MMP2/CD44 axes. Grifolin may develop as a promising lead compound for antitumor therapies by targeting energy metabolism regulator PGC1α signaling.
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