Jong Hyun Lee1, Chulwon Kim1, Seok-Geun Lee1, Woong Mo Yang1, Jae-Young Um1, Gautam Sethi2, Kwang Seok Ahn3. 1. College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea. 2. Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City, Vietnam; Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Vietnam; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore. Electronic address: gautam.sethi@tdt.edu.vn. 3. College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea. Electronic address: ksahn@khu.ac.kr.
Abstract
BACKGROUND: Ophiopogonin D (OP-D), a steroidal glycoside obtained from the Chinese medicinal plant Ophiopogonin japonicas (the root portion), has been traditionally used to treat fever, inflammation, cough, sputum etc. However, the detailed molecular mechanism(s) underlying its therapeutic actions is still unknown. HYPOTHESIS: Because nuclear factor-κB (NF-κB), PI3K/AKT, and activator protein-1 (AP-1) signaling cascades have significant functions in cell proliferation, inflammation, and angiogenesis in tumor cells, we hypothesized that OP-D may disrupt these signaling cascades to exert its anticancer effects in human lung-cancer cells. METHODS: We evaluated the effect of OP-D on multiple signaling cascades and its regulated functional responses in lung cancer cells. RESULTS: OP-D blocked both basal and cytokine-induced proliferation of human lung-cancer cells and caused down-regulation of the expression of diverse oncogenic gene products through the suppression of NF-κB, PI3K/AKT, and AP-1 pathways; but did not affect JNK, p38 and ERK MAP kinases. Interestingly, OP-D suppressed constitutive NF-κB activation in lung cancer cells via interfering with the IκB kinase activation, which inhibited phosphorylation and caused degradation of IκB-α. OP-D also blocked phosphorylation and the nuclear translocation of p65, thereby suppressing NF-κB reporter activity in lung cancer cells. Besides, OP-D could augment cell death induced by paclitaxel in lung-cancer cells. CONCLUSION: Overall, the data indicates that OP-D may abrogate diverse signaling cascades linked to tumorigenesis, and can be used in combination with chemotherapeutic agents for cancer therapy.
BACKGROUND: Ophiopogonin D (OP-D), a steroidal glycoside obtained from the Chinese medicinal plant Ophiopogonin japonicas (the root portion), has been traditionally used to treat fever, inflammation, cough, sputum etc. However, the detailed molecular mechanism(s) underlying its therapeutic actions is still unknown. HYPOTHESIS: Because nuclear factor-κB (NF-κB), PI3K/AKT, and activator protein-1 (AP-1) signaling cascades have significant functions in cell proliferation, inflammation, and angiogenesis in tumor cells, we hypothesized that OP-D may disrupt these signaling cascades to exert its anticancer effects in humanlung-cancer cells. METHODS: We evaluated the effect of OP-D on multiple signaling cascades and its regulated functional responses in lung cancer cells. RESULTS:OP-D blocked both basal and cytokine-induced proliferation of humanlung-cancer cells and caused down-regulation of the expression of diverse oncogenic gene products through the suppression of NF-κB, PI3K/AKT, and AP-1 pathways; but did not affect JNK, p38 and ERK MAP kinases. Interestingly, OP-D suppressed constitutive NF-κB activation in lung cancer cells via interfering with the IκB kinase activation, which inhibited phosphorylation and caused degradation of IκB-α. OP-D also blocked phosphorylation and the nuclear translocation of p65, thereby suppressing NF-κB reporter activity in lung cancer cells. Besides, OP-D could augment cell death induced by paclitaxel in lung-cancer cells. CONCLUSION: Overall, the data indicates that OP-D may abrogate diverse signaling cascades linked to tumorigenesis, and can be used in combination with chemotherapeutic agents for cancer therapy.