Mingzhu Li1, Shengbo Jin2, Yang Cao3, Jian Xu4, Shendong Zhu5, Zheng Li6. 1. Department of Integrated Traditional Chinese and Western Medicine Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning, China. 2. Traditional Therapy Center, Liaoning TCM Hospital, Liaoning, China. 3. Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning, China. 4. Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning, China. 5. Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning, China. 6. Department of Integrated Traditional Chinese and Western Medicine Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning, China. li189zheng@163.com.
Abstract
BACKGROUND: Non-small cell lung cancers (NSCLC) account for most cases of lung cancer. More effort is needed to research new drug and combination therapies for this disease. An anthraquinone derivative, emodin shows anticancer potency. We hypothesis that emodin suppresses lung cancer cells through hyaluronan (HA) synthase 2-HA-CD44/receptor for hyaluronic acid-mediated motility (RHAMM) interaction-dependent signaling pathway mediated cell cycle regulation. METHODS: We tested the effect of emodin on viability, apoptosis, and HA secretion of 5 NSCLC cell lines. We used NSCLC cells A549 for two rounds of knockdown study: (1) knocking down either the synthases (HAS2 and HAS3) or the receptors (CD44 and RHAMM); (2) knocking down either HAS2 or HAS3. Then determined the effect of emodin on viability, HA secretion, cell cycle, and expression of cyclin proteins. RESULTS: Emodin suppressed viability and HA secretion of all 5 NSCLC cell lines except for HA secretion of H460. Emodin had a slight apoptosis induction effect on all cell lines and was not different among cell lines. The knockdown of either the synthases or the receptors blocked emodin effects on viability while the knockdown of HAS2 block emodin effects but not HAS3. Emodin increased cells in the G1/G0 phase, and decreased cells in the S and G2/M phase by down-regulating cyclin A and B and up-regulating cyclin C, D, and E. HAS2 knockdown blocked the effects of emodin on the cell cycle. CONCLUSIONS: This study demonstrated that emodin regulates the cell cycle of NSCLC cells through the HAS2-HA-CD44/RHAMM interaction-dependent signaling pathway.
BACKGROUND:Non-small cell lung cancers (NSCLC) account for most cases of lung cancer. More effort is needed to research new drug and combination therapies for this disease. An anthraquinone derivative, emodin shows anticancer potency. We hypothesis that emodin suppresses lung cancer cells through hyaluronan (HA) synthase 2-HA-CD44/receptor for hyaluronic acid-mediated motility (RHAMM) interaction-dependent signaling pathway mediated cell cycle regulation. METHODS: We tested the effect of emodin on viability, apoptosis, and HA secretion of 5 NSCLC cell lines. We used NSCLC cells A549 for two rounds of knockdown study: (1) knocking down either the synthases (HAS2 and HAS3) or the receptors (CD44 and RHAMM); (2) knocking down either HAS2 or HAS3. Then determined the effect of emodin on viability, HA secretion, cell cycle, and expression of cyclin proteins. RESULTS:Emodin suppressed viability and HA secretion of all 5 NSCLC cell lines except for HA secretion of H460. Emodin had a slight apoptosis induction effect on all cell lines and was not different among cell lines. The knockdown of either the synthases or the receptors blocked emodin effects on viability while the knockdown of HAS2 block emodin effects but not HAS3. Emodin increased cells in the G1/G0 phase, and decreased cells in the S and G2/M phase by down-regulating cyclin A and B and up-regulating cyclin C, D, and E. HAS2 knockdown blocked the effects of emodin on the cell cycle. CONCLUSIONS: This study demonstrated that emodin regulates the cell cycle of NSCLC cells through the HAS2-HA-CD44/RHAMM interaction-dependent signaling pathway.
Authors: Qing Zhang; Wen Wen Chen; Xue Sun; Die Qian; Dan Dan Tang; Li Lin Zhang; Mei Yan Li; Lin Yu Wang; Chun-Jie Wu; Wei Peng Journal: Int J Biol Sci Date: 2022-05-16 Impact factor: 10.750