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7. Correction: Non-toxic dose of liposomal honokiol suppresses metastasis of hepatocellular carcinoma through destabilizing EGFR and inhibiting the downstream pathways

Author

Yang, Jianhong, primary, Pei, Heying, additional, Luo, Hong, additional, Fu, Afu, additional, Yang, Hansuo, additional, Hu, Jia, additional, Zhao, Chengjian, additional, Chai, LuLu, additional, Chen, Xiang, additional, Shao, Ximing, additional, Wang, Chunyu, additional, Wu, Wenshuang, additional, Wan, Li, additional, Ye, Haoyu, additional, Qiu, Qiang, additional, Peng, Aihua, additional, Wei, Yuquan, additional, Yang, Li, additional, and Chen, Lijuan, additional

Published
2020
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9. Non-toxic dose of liposomal honokiol suppresses metastasis of hepatocellular carcinoma through destabilizing EGFR and inhibiting the downstream pathways

Author

Yang, Jianhong, primary, Pei, Heying, additional, Luo, Hong, additional, Fu, Afu, additional, Yang, Hansuo, additional, Hu, Jia, additional, Zhao, Chengjian, additional, Chai, LuLu, additional, Chen, Xiang, additional, Shao, Ximing, additional, Wang, Chunyu, additional, Wu, Wenshuang, additional, Wan, Li, additional, Ye, Haoyu, additional, Qiu, Qiang, additional, Peng, Aihua, additional, Wei, Yuquan, additional, Yang, Li, additional, and Chen, Lijuan, additional

Published
2016
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10. Barbigerone, a natural isoflavone, induces apoptosis in murine lung-cancer cells via the mitochondrial apoptotic pathway

Author

Zhixing Cao, Peng Aihua, Xia Zhao, Yu-Zhu Zheng, Zheng-Guang Li, Lijuan Chen, Pei-Du Jiang, Haoyu Ye, Yinglan Zhao, Xiaohua Wu, Yuquan Wei, and Yong-qiu Mao

Subjects
MAPK/ERK pathway, Lung Neoplasms, Time Factors, Physiology, Antineoplastic Agents, Apoptosis, Biology, Mice, Downregulation and upregulation, Cell Line, Tumor, Animals, Phosphorylation, Protein kinase A, Protein kinase B, bcl-2-Associated X Protein, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Dose-Response Relationship, Drug, Caspase 3, Cytochromes c, Isoflavones, In vitro, Caspase 9, Cell biology, Mitochondria, Gene Expression Regulation, Proto-Oncogene Proteins c-bcl-2, Cancer cell, Cancer research, Proto-Oncogene Proteins c-akt
Abstract

Barbigerone is a naturally occurring isoflavone with antioxidant activity. In present study, we investigated the antitumor activity of barbigerone against murine lung cancer cells LL/2 and the possible mechanism in vitro. Our results showed that barbigerone inhibited LL/2 cells proliferation in a concentration- and time-dependent manner and caused apoptotic death of LL/2 cells. Barbigerone-induced apoptosis was characterized by enhanced mitochondrial cytochrome c release, activation of caspase-3,-9, but not caspase-8. Exposure of LL/2 cells to barbigerone resulted in upregulation of Bcl-2-associated protein (Bax) and down-regulation of Bcl-2. In addition, proliferation inhibitory effect of barbigerone was associated with decreased level of phosphorylated p42/44 mitogen-activated protein kinase (p42/44 MAPK) and phosphorylated Akt. Moreover, barbigerone exhibit less toxicity to non-cancer cells than tumor cells. In conclusion, our results indicated that barbigerone can inhibit murine lung cancer cell proliferation by inducing apoptosis via mitochondrial apoptotic pathway and by decreasing phosphorylated p42/44 MAPK and Akt. Its potential to be a candidate of anti-cancer agent is worth being further investigated.

Published
2009

16. Non-toxic dose of liposomal honokiol suppresses metastasis of hepatocellular carcinoma through destabilizing EGFR and inhibiting the downstream pathways.

Author

Yang J, Pei H, Luo H, Fu A, Yang H, Hu J, Zhao C, Chai L, Chen X, Shao X, Wang C, Wu W, Wan L, Ye H, Qiu Q, Peng A, Wei Y, Yang L, and Chen L

Subjects
Animals, Apoptosis drug effects, Carcinoma, Hepatocellular pathology, Cell Cycle drug effects, Cell Line, Tumor, Cell Movement drug effects, Cell Proliferation drug effects, Disease Models, Animal, Female, Hep G2 Cells, Heterografts, Humans, Liver Neoplasms pathology, MAP Kinase Signaling System drug effects, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 9 metabolism, Melanoma, Experimental, Mice, Neoplasm Metastasis, Neoplasm Staging, Protein Stability drug effects, Zebrafish, cdc42 GTP-Binding Protein antagonists & inhibitors, rac1 GTP-Binding Protein antagonists & inhibitors, Antineoplastic Agents administration & dosage, Biphenyl Compounds administration & dosage, Carcinoma, Hepatocellular metabolism, ErbB Receptors metabolism, Lignans administration & dosage, Liver Neoplasms metabolism, Signal Transduction drug effects
Abstract

At present, there is no specific anti-metastasis drug in HCC treatment. Drugs used for primary HCC tumors and tumor metastasis are very similar, among which cytotoxic drugs are prevalent, such as cisplatin, doxorubicin and 5-FU. The EGFR pathway plays an important role in promoting hepatocellular carcinoma (HCC) metastasis. Hence, development of non-toxic anti-metastasis drugs, such as EGFR or downstream pathways inhibitors, is of great importance. In our present study, we found non-toxic dose of liposomal honokiol (LH) could inhibit the HCC metastasis by destabilizing EGFR and inhibiting the downstream pathways. Non-toxic dose of LH significantly inhibited the motility, migration and lamellipodia formation of HepG2 cells in vitro and decreased extravasation of HepG2 cells in a novel metastasis model of transgenic zebrafish. In two lung metastasis models (HepG2 and B16F10) and a spontaneous metastasis model of HepG2 cells, LH remarkably inhibited pulmonary metastasis and regional lymph nodes metastasis without obvious toxicity. Further study showed that destabilizing EGFR and inhibiting the downstream pathways were the main mechanisms of non-toxic dose of LH on metastasis inhibition. Our results provide the preclinical rationale and the underlying mechanisms of LH to suppress HCC metastasis, implicating LH as a potential therapeutic agent to block HCC metastasis without severe side effects.

Published
2017
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