Induces G2/M cell cycle arrest Induces intrinsic apoptotic pathway via activation of caspase-3 and caspase-9, cytochrome c release from mitochondria, and PARP cleavage
Induces G2/M cell cycle arrest associated with decline of cyclin B1 protein and phosphorylation of ATM/Chk1, induced apoptosis via expression of Fas (CD95)/Fas ligand (CD95L), with the activation of caspase-8
Stimulates time- and dose-dependent proliferation of mice cells and human PBMC Upregulates human cytokine (interleukin, IL-2 and IL-12) immunomodulatory
Suppresses TPA-induced LOX-1 mRNA expression Attenuates expression of SR-A, SR-PSOX, and CD-36 and led to block DiI-AcLDL uptake Inhibits AP-1 and NF-κB transcriptional activity
Marked upregulation of multiple HSPs, such as HSP40 and HSP70HSPs Increases proteasome activity with upregulation of 5, a major proteasome functional protein Upregulates expressions of several proautophagic markers, including p62 and microtubule-associated protein 1 light-chain 3 (LC3)-II Suppresses cellular protein modifications by 4-hydroxy-2-nonenal (HNE) Confers resistance to toxicity of HNE via p62 induction Induces ubiquitination and aggregation of cellular proteins Activates ubiquitin-proteasome system and autophagy
Activates phase II drug metabolizing enzymes, such as GST (glutathione S-transferase), epoxide hydrolase, and hemeoxygenase via the transcription factor Nrf2 dependent pathway
Enhances TRAIL-induced apoptosis Causes activations of caspase-8, caspase-9, caspase-3 and PARP in combination with TRAIL Induces expression of TRAIL receptors DR4 and DR5 Downregulates expression of antiapoptotic protein c-FLIP Causes activation of ERK in time-dependent manner
ZER derivatives (5, 10, 14, and 20) showed antiproliferative activity
Breast
Human breast adenocarcinoma cell lines (MCF-7 and MDA-MB 231) [68, 90] Human breast benign cell line (MCF-10A) [76]
G2/M phase cell cycle arrest Downregulates cyclin B1, cyclin-dependent kinase 1, Cdc25C, and Cdc25B and Bax/Bak-mediated apoptosis Induces significant expression of DR4 Activation of Bax and Bak
Inhibits PaCa-associated angiogenesis through the inhibition of NF-κB and NF-κB-dependent proangiogenic gene products
Lung
Human nonsmall cell lung carcinoma (H1299 cells) [63, 90]
Enhances TNF-induced cytotoxicity and potentiates apoptosis Inhibits TNF-induced IκBα protein degradation and phosphorylation Inhibits TNF-induced phosphorylation of p65 protein Suppresses TNF-induced invasion activity
ZER derivative (parent alcohol 8) could protect irradiation induced cell apoptosis and DNA damage, at least partly, via activation of Keap1/Nrf2/ARE pathway
Normal African green monkey kidney cells (Vero) [97]
Inhibits NF-κB and IκBα kinase activation Suppresses antiapoptotic and metastatic gene expression Upregulates apoptosis and downregulates cancer invasion
Inhibits RANKL-induced NF-κB activation through inhibition of activation of IKBA kinase, IKBA phosphorylation, and IKBA degradation Suppresses RANKL-induced differentiation of an osteoclast precursor cells to osteoclasts Inhibits osteoclastogenesis induced by RANKL and tumor (RAW264.7) cells after incubation in the presence of MDA-MB-231 cells or U266 cells for 24 h, then exposed to ZER for 5 days, and finally stained for TRAP expression) Potential therapeutic agent for osteoporosis and cancer-associated bone loss
