Table 1.
Antitumor activity of Viscum species—in vitro studies
| Mechanism of action | Preparation/compound (host tree) | Concentration of the extract/compound | Cell line | Observations | References |
|---|---|---|---|---|---|
| Cell cycle | Viscum album L. (apple tree) |
Extract containing 10 ng/mL lectin MLI Extract containing 60 µg/mL oleanolic acid Extract containing 5 ng/mL lectin MLI and 50 µg/mL oleanolic acid |
Human osteosarcoma cell lines 143B, Saos-2 and U2OS | G1 arrest in TP53 wild-type (U2OS) and null-mutant (Saos-2) cells, S arrest in TP53 mutant cells (143B), blockage of G1/S transition accompanied by downregulation of CDK4, CCND1, CDK2, CCNE, CCNA, investigations on the transcriptional level revealed secondary TP53 participation, cell cycle arrest was mediated by transcriptionally increased expression of GADD45A and CDKN1A and decreased SKP2 levels | Kleinsimon et al. (2018) |
| Viscum album L | 3% and 5% v/v | Murine melanoma cell line B16F10 | Increased Sub G0 population, probably associated with a consistent decrease in G1, and an increase in S or G2/M populations | Melo et al. (2018) | |
| Viscum articulatum Burm. f. (Dalbergia latifolia Roxb.) | 0.015–150 µg/mL | Human leukemia cell lines Jurkat E6.1 and THP1 | G2/M cell cycle arrest with a concomitant decrease in some cells at G0/G1 phase | Mishra et al. (2018) | |
| 1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one isolated from Viscum coloratum (Kom.) Nakai | 2.5–20 µM | Human lung cancer cell lines A549 and NCI-H292 | Cell cycle arrest in A549 and NCI- H292 cells at the S and G0/G1 phases, respectively | Fan et al. (2019) | |
| Viscum coloratum (Kom.) Nakai |
Lectin 10–1000 ng/mL Extract 10–1000 µg/mL |
Mouse melanoma cell lines B16BL6 and B16F10 | G0/G1 cell cycle arrest | Han et al. (2015) | |
| MMP | Viscum articulatum Burm. f. (Dalbergia latifolia Roxb.) | 0.015–150 µg/mL | Human leukemia cell lines Jurkat E6.1 and THP1 | Loss of MMP, which is required for cytochrome c release | Mishra et al. (2018) |
|
Viscum album L (apple tree) |
Extract containing 1.25–7.5 ng/mL lectin MLI Extract containing 30–45 µg/mL oleanolic acid Extract containing 1.25–7.5 ng/mL lectin MLI and 30–45 µg/mL oleanolic acid |
Human alveolar Rhabdomyosarcoma cell line RMS-13 | Stammer et al. (2017) | ||
|
Viscum album L (apple tree) |
Extract containing 1–40 ng/mL lectin MLI Extract containing 10–60 µg/mL oleanolic acid Extract containing 1–40 ng/mL lectin MLI and 10–60 µg/mL oleanolic acid |
Human Ewing sarcoma cell lines TC-71 and MHH-ES-1 | Twardziok et al. (2016) | ||
| Viscum album L. (apple tree) |
Extract containing 2–16 ng/mL lectin MLI Extract containing 20–40 µg/mL oleanolic acid Extract containing 2–16 ng/mL lectin MLI and 20–40 µg/mL oleanolic acid |
Human acute myeloid leukemia cell lines U937 and HL-60 | Delebinski et al. (2015) | ||
| 1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one isolated from Viscum coloratum (Kom.) Nakai | 2.5–20 µM | Human lung cancer cell lines A549 and NCI-H292 | Fan et al. (2019) | ||
| Viscum album L. (apple tree) |
Extract containing 2.5–10 ng/mL lectin MLI Extract containing 40–60 µg/mL oleanolic acid Extract containing 2.5–10 ng/mL lectin MLI and 40–60 µg/mL oleanolic acid |
Human osteosarcoma cell lines 143B and Saos-2 | Kleinsimon et al. (2017) | ||
| Cytochrome c and AIF | Viscum album L. (apple tree) |
Extract containing 4–8 ng/mL lectin MLI Extract containing 25–35 µg/mL oleanolic acid Extract containing 4–8 ng/mL lectin MLI and 25–35 µg/mL oleanolic acid |
Human acute myeloid leukemia cell lines U937 and HL-60 | Release of cytochrome c | Delebinski et al. (2015) |
| 1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one isolated from Viscum coloratum (Kom.) Nakai | 2.5–20 µM | Human lung cancer cell lines A549 and NCI-H292 | Release of cytochrome c and AIF | Fan et al. (2019) | |
| MAPK/JNK, ERK and p38 | Lectin II isolated from Viscum coloratum (Kom.) Nakai | 100 ng/mL | Human myeloid leukemia cell line U937 | Increased phosphorylation of the JNK1 substrate, GST-c-Jun N-terminal protein | Park et al. (2000) |
| AbnobaViscum F (ash) | 20 µg/mL | Human myeloid leukemia cell line K562 | Increased phosphorylation of JNK1 and p38, reduced levels of phosphorylated ERK-1/2 | Park et al. (2012) | |
| Viscum album L. (apple tree) |
Extract containing 1–40 ng/mL lectin MLI Extract containing 10–60 µg/mL oleanolic acid Extract containing 1–40 ng/mL lectin MLI and 10–60 µg/mL oleanolic acid |
Human Ewing sarcoma cell lines TC-71 and MHH-ES-1 | Increased phosphorylation of JNK1 and p38 | Twardziok et al. (2017) | |
| Viscum album L. (apple tree) |
Extract containing 10 ng/mL lectin MLI Extract containing 60 µg/mL oleanolic acid Extract containing 5 ng/mL lectin MLI and 50 µg/mL oleanolic acid |
Human osteosarcoma cell lines 143B, Saos-2 and U2OS | Activation of JNK1 with simultaneous inactivation of ERK-1/2 | Kleinsimon et al. (2018) | |
| 1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one isolated from Viscum coloratum (Kom.) Nakai | 2.5–20 µM | Human lung cancer cell lines A549 and NCI-H292 | Upregulation of the expression levels of p-ERK1/2 and p-P90RSK | Fan et al. (2019) | |
| PI3K/AKT | 1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one isolated from Viscum coloratum (Kom.) Nakai | 2.5–20 µM | Human lung cancer cell lines A549 and NCI-H292 | Downregulation of the phosphorylation of AKT and P70RSK | Fan et al. (2019) |
| Lectin isolated from Viscum coloratum (Kom.) Nakai | 10 ng/mL | Human cancer cell line A253 | Dephosphorylation of AKT | Choi et al. (2004) | |
|
Iscador Qu Spezial (oak) Iscador M (apple tree) |
0.3 mg/mL | Human tongue cancer cell lines SCC9 and SCC25 | Reduced pAKT | Klingbeil et al. (2013) | |
| AbnobaViscum F (ash) | 20 µg/mL | Human myeloid leukemia cell line K562 | Reduced levels of phosphorylated AKT | Park et al. (2012) | |
| COX-2 | VA Qu Spez (oak) | 10–100 µg/mL | Human lung adenocarcinoma cell line A549 | Inhibition of the secretion of IL-1β-induced PGE2 associated with a reduced expression of COX-2 | Hegde et al. (2011) and Saha et al. (2015) |
| Caspases | Viscum album L. (apple tree) |
Extract containing 2–16 ng/mL lectin MLI Extract containing 20–40 µg/mL oleanolic acid Extract containing 2–16 ng/mL lectin MLI and 20–40 µg/mL oleanolic acid |
Human acute myeloid leukemia cell line HL-60 | Activation of caspase-8 and caspase -9 | Delebinski et al. (2015) |
| Viscum articulatum Burm. f. (Dalbergia latifolia Roxb.) | 0.015–150 µg/mL | Human leukemia cell lines Jurkat E6.1 and THP1 | Activation of caspase-8 and caspase-3 | Mishra et al. (2018) | |
| Viscum album L. (apple tree) |
Extract containing 1.25–7.5 ng/mL lectin MLI Extract containing 30–45 µg/mL oleanolic acid Extract containing 1.25–7.5 ng/mL lectin MLI and 30–45 µg/mL oleanolic acid |
Human alveolar Rhabdomyosarcoma cell line RMS-13 | Activation of caspase-9, caspase-8 and caspase-3 | Stammer et al. (2017) | |
| Viscum album L. (apple tree) |
Extract containing 1–40 ng/mL lectin MLI Extract containing 10–60 µg/mL oleanolic acid Extract containing 1–40 ng/mL lectin MLI and 10–60 µg/mL oleanolic acid |
Human Ewing sarcoma cell lines TC-71 and MHH-ES-1 | Activation of caspase-9, caspase-8 | Twardziok et al. (2016) | |
| 1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one isolated from Viscum coloratum (Kom.) Nakai | 2.5–20 µM | Human lung cancer cell lines A549 and NCI-H292 | Activation of caspase-9 and caspase-3 | Fan et al. (2019) | |
| AbnobaViscum F (ash) | 20 µg/mL | Human myeloid leukemia cell line K562 | Decreased expression of procaspase-9 but increased that of cleaved (active) caspase-9 | Park et al. (2012) | |
| Lectin isolated from Viscum coloratum (Kom.) Nakai | 10 ng/mL | Human cancer cell line A253 | Activation of caspase-3 | Choi et al. (2004) | |
| Viscum album L. (apple tree) |
Extract containing 2.5–10 ng/mL lectin MLI Extract containing 40–60 µg/mL oleanolic acid Extract containing 2.5–10 ng/mL lectin MLI and 40–60 µg/mL oleanolic acid |
Human osteosarcoma cell lines 143B and Saos-2 | Activation of caspase-8 and caspase-9 | Kleinsimon et al. (2017) | |
| Viscum Coloratum (Kom.) Nakai |
Lectin 10–1000 ng/mL Extract 10–1000 µg/mL |
Mouse melanoma cell lines B16BL6 and B16F10 | Activation of caspase-1, 3, 4, 5, 6, 7, 8, and 9 | Han et al. (2015) | |
| Antiapoptotic proteins | Viscum album L. (apple tree) |
Extract containing 40 ng/mL lectin MLI Extract containing 40 µg/mL oleanolic acid Extract containing 15 ng/mL lectin MLI and 30 µg/mL oleanolic acid |
Human acute myeloid leukemia cell line HL-60 | Downregulation of BIRC5, XIAP, p53 and claspin | Delebinski et al. (2015) |
| Viscum album L. (apple tree) |
Extract containing 1–40 ng/mL lectin MLI Extract containing 10–60 µg/mL oleanolic acid Extract containing 1–40 ng/mL lectin MLI and 10–60 µg/mL oleanolic acid |
Human Ewing sarcoma cell lines TC-71 and MHH-ES-1 | Downregulation of BIRC5, XIAP, MCL1 and CLSPN, | Twardziok et al. (2016) | |
| Viscum album L. (apple tree) |
Extract containing 2.5–10 ng/mL lectin MLI Extract containing 40–60 µg/mL oleanolic acid Extract containing 2.5–10 ng/mL lectin MLI and 40–60 µg/mL oleanolic acid |
Human osteosarcoma cell lines 143B and Saos-2 | Downregulation of BIRC5, XIAP, BCL2, and CLSPN | Kleinsimon et al. (2017) | |
| Viscum album L. (apple tree) |
Extract containing 5 ng/mL lectin MLI Extract containing 40 µg/mL oleanolic acid Extract containing 5 ng/mL lectin MLI and 40 µg/mL oleanolic acid |
Human alveolar Rhabdomyosarcoma cell lines RH-30 and RMS-13 | Downregulation of BIRC5, XIAP, BCL2, BCL2L1 and MCL1 | Stammer et al. (2017) | |
| Viscum articulatum Burm. f. (Dalbergia latifolia Roxb.) | 0.015–150 µg/mL | Human leukemia cell lines Jurkat E6.1 and THP1 | Downregulation of BCL2 | Mishra et al. (2018) | |
| Lectin isolated from Viscum coloratum (Kom.) Nakai | 10 ng/mL | Human hepatocarcinoma cells SK-Hep-1 and Hep3B | Lyu et al. (2002) | ||
| AbnobaViscum F (ash) | 20 µg/mL | Human myeloid leukemia cell line K562 | Downregulation of Mcl-1 | Park et al. (2012) | |
| 1,7-bis(4-hydroxyphenyl)-1,4-heptadien-3-one isolated from Viscum coloratum (Kom.) Nakai | 2.5–20 µM | Human lung cancer cell lines A549 and NCI-H292 | Upregulation of Bcl-2 and Bcl-xL | Fan et al. (2019) | |
| Proapoptotic proteins | Viscum articulatum Burm. f. (Dalbergia latifolia Roxb.) | 0.015–150 µg/mL | Human leukemia cell lines Jurkat E6.1 and THP1 | Upregulation of Bax | Mishra et al. (2018) |
| Lectin isolated from Viscum coloratum (Kom.) Nakai | 10 ng/mL | Human hepatocarcinoma cells SK-Hep-1 and Hep3B | Lyu et al. (2002) | ||
| Viscum album L. (apple tree) |
Extract containing 2.5–10 ng/mL lectin MLI Extract containing 40–60 µg/mL oleanolic acid Extract containing 2.5–10 ng/mL lectin MLI and 40–60 µg/mL oleanolic acid |
Human osteosarcoma cell lines 143B and Saos-2 | Kleinsimon et al. (2017) | ||
| 1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one isolated from Viscum coloratum (Kom.) Nakai | 2.5–20 µM | Human lung cancer cell lines A549 and NCI-H292 | Downregulation of Bax | Fan et al. (2019) | |
| STAT3 | Viscum album L. (apple tree) |
Extract containing 10 ng/mL lectin MLI Extract containing 60 µg/mL oleanolic acid Extract containing 5 ng/mL lectin MLI and 50 µg/mL oleanolic acid |
Human osteosarcoma cell lines 143B, Saos-2 and U2OS | Dephosphorylation of STAT3 at Tyr705 and Ser727, down-regulation of total STAT3 and its direct downstream targets BIRC5 and C-MYC | Kleinsimon et al. (2018) |
| AbnobaViscum F (ash) | 5–20 µg/mL | Human hepatocellular carcinoma cell line Hep3B | Reduction of C-MYC protein levels which might be mediated by the ubiquitin–proteasome system | Yang et al. (2019) | |
| Telomerase | Lectin isolated from Viscum coloratum (Kom.) Nakai | 10 ng/mL | Human cancer cell line A253 | Inhibition of telomerase activity through downregulation of hTERT | Choi et al. (2004) |
| ROS | Viscum articulatum Burm. f. (Dalbergia latifolia Roxb.) | 0.015–150 µg/mL | Human leukemia cell lines Jurkat E6.1 and THP1 | ROS mediated DNA fragmentation | Mishra et al. (2018) |
| 1,7-Bis(4-hydroxyphenyl)-1,4-heptadien-3-one isolated from Viscum coloratum (Kom.) Nakai | 5–20 µM | Human lung cancer cell lines A549 and NCI-H292 | Promotion of ROS generation | Fan et al. (2019) |