Table 1.
Apoptotic activity of icariin and its derivatives.
| Compound | Cell Line | Study Type | Mechanism | References |
|---|---|---|---|---|
| Icariin | Human lung adenocarcinoma cells (A459) | In vitro and In vivo | Activation of ERS signaling, increased expression of ERS-related molecules (p-ERK, ATF6, GRP78, p-eIF2α, and CHOP, downregulation of Bcl2 expression and upregulation of PUMA | Di et al., 2015 |
| Human esophageal cancer cells (EC109 and TE1) | In vitro and In vivo | Activation of ERS signaling, increased expression of ERS-related molecules (p-ERK, ATF4, GRP78, p-eIF2α, and CHOP, downregulation of Bcl2 expression and upregulation of PUMA | Fan et al., 2016 | |
| Human hepatoma cells (SMMC-7721, Bel-7402, and HepG2) | In vitro and In vivo | Activation of ROS/JNK-dependent mitochondrial pathway that involved the generation of ROS and JNK activation, resulted in enhanced Bax-to-Bcl-2 ratio, loss of mitochondrial membrane potential, cytochrome c release, and caspase cascade | Li et al., 2010 | |
| Mouse tumor Leydig cells (MLTC-1) | In vitro | Activation of caspase-9, -3, enhanced Bax/Bcl-2 ratio, and release of cytochrome c, as well as down-regulation of the expression of piwil4 | Wang et al., 2011a | |
| Icaritin | Hepatocellular Carcinoma (HepG2) | In vitro | Enhanced Bax/Bcl-2 ratio, activation of caspase-3, activation of JNK1 signaling | He et al., 2010 |
| Leukemia cells (Primary acute myeloid leukemia cells, NB4, HL60, and U937) | In vitro | Activation of caspase-9, -3, -7, cleavage of PARP, downregulation of c-myc, inhibition of MAPK/ERK, and PI3K/AKT signals. | Li et al., 2013a | |
| Human Burkitt lymphoma cells (Raji and P3HR-1) | In vitro | Activation of caspase-8, -9, cleavage of PARP, downregulation of c-myc and enhanced Bax/Bcl-2 ratio | Li et al., 2014b | |
| Human liver cells (L02) and Human hepatocarcinoma cells (SMMC-7721) | In vitro | Activation of caspase-3, -8, enhanced Bax/Bcl-2 ratio, increased expression levels of Fas | Sun et al., 2015b | |
| Human endometrial cancer cells (Hec1A) | In vitro | Activation of caspase-3 and caspase-9, cleavage of PARP, release of cytochrome c, enhanced Bax/Bcl-2 ratio, and sustained activation ERK1/2 signaling | Tong et al., 2011 | |
| Extranodal NK/T-cell lymphoma cells (SNK-10 and SNT-8) | In vitro | Activation of caspase-3 and caspase-9, enhanced Bax/Bcl-2 ratio, downregulation of p-Bad, inhibition of Jak/Stat3, and PI3K/Akt signaling pathway mediated by reduced expression of LMP1 | Wu et al., 2015b | |
| Leukemia cells (Primary chronic myeloid leukemia cells and K562) | In vitro and In vivo | Activation of caspase-3, -9, release of cytochrome c, enhanced Bax/Bcl-2 ratio, downregulated expression of Apaf-1, inhibition of MAPK/ERK/JNK signals and down-regulated kinase activity of Jak-2/STAT3/Akt signal network | Zhu et al., 2011 | |
| Icariside II | Human hepatoblastoma cells (HepG2), Mouse liver carcinoma cells (H22) | In vitro and In vivo | Mitochondrion membrane and lysomal membrane permeabilization, activation of caspase-3, -7, -8, -9, cleavage of PARP, enhanced Bax/Bcl-2 ratio. | Geng et al., 2015 |
| Human breast cancer cells (MCF-7) | In vitro | Activation of caspase-8, -9, decreased mitochondrial potential, release of cytochrome C and AIF, increased expression of Fas and FADD as well as increased expression of Bax and BimL | Huang et al., 2012 | |
| Human acute myeloid leukemia cells (U937) | In vitro | Activation of caspase-3, cleavage of PARP, and decreased bcl-xL and survivin, inactivation of STAT3-related signaling pathway. | Kang et al., 2012 | |
| Multiple myeloma cells (U266) | In vitro | Down-regulation of expression of Bcl-2, Bcl-xL, survivin, Cyclin D1, COX-2, and VEGF, enhanced PARP cleavage and caspase-3 activation, inhibition of STAT3 activation and enhanced expression of SHP-1 and PTEN through inhibiting JAK2 and c-Src | Kim et al., 2011 | |
| Human prostate cancer cells (PC-3) | In vitro | Activation of caspase-8, -9, -3, cleavage of PARP, decreased mitochondrial potential, COX-2, iNOS, and VEGF expression, release of cytochrome C, inhibition of COX-2/PGE2 pathway | Lee et al., 2009 | |
| Human non-small cell lung cancer cells (A549) | In vitro | Activation of caspase-3, -9, cleavage of PARP, release of cytochrome c, enhanced Bax/Bcl-2 ratio, Activation of ROS/MAPK pathway that involved activation of ROS downstream effectors, JNK and p38MAPK | Song et al., 2012 | |
| Human eosophageal squamous carcinoma (Eca109) | In vitro and In vivo | Downregulation of survivin and Cyclin D1, inhibition of β-catenin-dependent signaling. | Wang et al., 2011b | |
| Human epidermoid carcinoma cells (A431) | In vitro | Activation of caspase-9, cleavage of PARP, inhibition of JAK/STAT3 and MAPK-ERK pathways, activation of PI3K/AKT pathway, inhibition of EGF-induced activation of EGFR pathway. | Wu et al., 2013b | |
| Human melanoma cells (A375 and SK-MEL-5) and Mouse melanoma cells (B16) | In vitro and In vivo | Activation of caspase-3, decreased expression of survivin, inhibition of JAK/STAT3 and MAPK pathways as well as activation of PI3K/AKT pathway | Wu et al., 2013a |