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Cochinchina momordica seed suppresses proliferation and metastasis in human lung cancer cells by regulating multiple molecular targets.
Am J Chin Med. 2015; 43(1):149-66.AJ

Abstract

Cochinchina Momordica Seed, which is the dried ripe seed of Momordica cochinchinensis (Lour.) Spreng, has been used as a mainly anticancer ingredient for many years in China. This study aims at investigating the roles of an ethanol-soluble extract of Cochinchina Momordica Seed (ECMS) in suppressing the proliferation and metastasis of human lung cancer cells, and further elucidating underlying molecular mechanisms. Our researches suggest that ECMS dose-dependently decreased the survival rates of A549 and H1299 cells, and inhibited the migration and invasion in A549 cells. ECMS-induced apoptosis was accompanied by up-regulation of p53, Bax and the down-regulation of Bcl-2, PI-3K/Akt signal pathway, and resulted in the dissipation of mitochondrial membrane potential (ΔΨm) and sequentially activated caspase-3 cascade. Pre-treated with specific inhibitors, LY294002 (PI-3K inhibitor) and BAY11-7082 (NF-κB inhibitor) could enhance the anti-proliferation effects of ECMS on A549 cells. Furthermore, ECMS could increase the level of E-cadherin and decrease of the level of STAT-3 and MMP-2, and scarcely affected the expression of VEGF, and resulted in the inhibition of migration and invasion. Pre-treated with specific inhibitors, WP1066 (STAT-3 inhibitor) and TIMP-2 (MMP-2 inhibitor) could enhance the inhibitory effects of ECMS on migration. In conclusion, the current data demonstrated ECMS inhibited the proliferation of A549 cells by inducing apoptosis, at least partly through the activation of p53 and inactivation of PI-3K/Akt signaling. STAT-3 and MMP-2 pathways may be partly involved in anti-metastasis activities of ECMS. Hence, ECMS might be a promising candidate for the therapy of the non-small cell lung cancer by regulating multiple molecular targets.

Authors+Show Affiliations

Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiaotong University, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25649746

Citation

Shen, Yang, et al. "Cochinchina Momordica Seed Suppresses Proliferation and Metastasis in Human Lung Cancer Cells By Regulating Multiple Molecular Targets." The American Journal of Chinese Medicine, vol. 43, no. 1, 2015, pp. 149-66.
Shen Y, Meng L, Sun H, et al. Cochinchina momordica seed suppresses proliferation and metastasis in human lung cancer cells by regulating multiple molecular targets. Am J Chin Med. 2015;43(1):149-66.
Shen, Y., Meng, L., Sun, H., Zhu, Y., & Liu, H. (2015). Cochinchina momordica seed suppresses proliferation and metastasis in human lung cancer cells by regulating multiple molecular targets. The American Journal of Chinese Medicine, 43(1), 149-66. https://doi.org/10.1142/S0192415X1550010X
Shen Y, et al. Cochinchina Momordica Seed Suppresses Proliferation and Metastasis in Human Lung Cancer Cells By Regulating Multiple Molecular Targets. Am J Chin Med. 2015;43(1):149-66. PubMed PMID: 25649746.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cochinchina momordica seed suppresses proliferation and metastasis in human lung cancer cells by regulating multiple molecular targets. AU - Shen,Yang, AU - Meng,Linyi, AU - Sun,Huajun, AU - Zhu,Yizhun, AU - Liu,Hongrui, Y1 - 2015/02/04/ PY - 2015/2/5/entrez PY - 2015/2/5/pubmed PY - 2015/9/22/medline KW - Apoptosis KW - Cochinchina Momordica Seed KW - Human Lung Cancer Cell KW - Signaling Pathway SP - 149 EP - 66 JF - The American journal of Chinese medicine JO - Am J Chin Med VL - 43 IS - 1 N2 - Cochinchina Momordica Seed, which is the dried ripe seed of Momordica cochinchinensis (Lour.) Spreng, has been used as a mainly anticancer ingredient for many years in China. This study aims at investigating the roles of an ethanol-soluble extract of Cochinchina Momordica Seed (ECMS) in suppressing the proliferation and metastasis of human lung cancer cells, and further elucidating underlying molecular mechanisms. Our researches suggest that ECMS dose-dependently decreased the survival rates of A549 and H1299 cells, and inhibited the migration and invasion in A549 cells. ECMS-induced apoptosis was accompanied by up-regulation of p53, Bax and the down-regulation of Bcl-2, PI-3K/Akt signal pathway, and resulted in the dissipation of mitochondrial membrane potential (ΔΨm) and sequentially activated caspase-3 cascade. Pre-treated with specific inhibitors, LY294002 (PI-3K inhibitor) and BAY11-7082 (NF-κB inhibitor) could enhance the anti-proliferation effects of ECMS on A549 cells. Furthermore, ECMS could increase the level of E-cadherin and decrease of the level of STAT-3 and MMP-2, and scarcely affected the expression of VEGF, and resulted in the inhibition of migration and invasion. Pre-treated with specific inhibitors, WP1066 (STAT-3 inhibitor) and TIMP-2 (MMP-2 inhibitor) could enhance the inhibitory effects of ECMS on migration. In conclusion, the current data demonstrated ECMS inhibited the proliferation of A549 cells by inducing apoptosis, at least partly through the activation of p53 and inactivation of PI-3K/Akt signaling. STAT-3 and MMP-2 pathways may be partly involved in anti-metastasis activities of ECMS. Hence, ECMS might be a promising candidate for the therapy of the non-small cell lung cancer by regulating multiple molecular targets. SN - 1793-6853 UR - https://www.unboundmedicine.com/medline/citation/25649746/Cochinchina_momordica_seed_suppresses_proliferation_and_metastasis_in_human_lung_cancer_cells_by_regulating_multiple_molecular_targets_ L2 - https://www.worldscientific.com/doi/10.1142/S0192415X1550010X?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -