Anti-Cancer Activities of Diterpenoids Derived from Euphorbia fischeriana Steud
Abstract
:1. Introduction
2. Chemical Structure of Diterpenoids
3. Anticancer Activities of Diterpenoids
4. The Anti-Cancer Mechanism of Diterpenoids
4.1. Induction of Apoptosis
4.2. Cell Cycle Arrest
4.3. Inhibition of Metastasis
5. Conclusions and Future Perspectives
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available or not from the authors. |
No. | Compound | Subtype | Type of Cancer | Cell Lines ((IC50) | Ref. |
---|---|---|---|---|---|
1 | jolkinolide B | ent-abietane | liver | HepG-2 (24.43 μM/48 h) | [16] |
breast | MCF-7 (22.76 μM/48 h) | [16,17] | |||
breast | MDA-MB-231 | [18] | |||
gastric | SGC-7901 (31.32 μM/48 h) | [16] | |||
gastric | BGC-823 (32.45 μM/48 h) | [16] | |||
gastric | MGC-803 (34.7 μM/48 h) | [16] | |||
cervical | Hela (23.12 μM/48 h) | [16] | |||
human leukemic | U937 | [19] | |||
human leukemic | K562 (12.1 μg/mL/24 h) | [20] | |||
human leukemic | K562 (11.3 μg/mL/48 h) | [20] | |||
human leukemic | K562 (10.7 μg/mL/72 h) | [20] | |||
human leukemic | THP-1 | [21] | |||
human leukemic | HL-60 | [21] | |||
lung | A549 (28.24 μM) | [22] | |||
melanoma | B16F10 | [23] | |||
prostate | LNCaP (40 μM/48 h) | [24] | |||
prostate | DU145 (145 μM/48 h) | [24] | |||
prostate | PC3 (244 μM/48 h) | [24] | |||
2 | jolkinolide A | ent-abietane | liver | HepG-2 (80.12 μM/48 h) | [16] |
breast | MCF-7 (56.34 μM/48 h) | [16] | |||
lung | A549 | [22] | |||
gastric | SGC-7901 (>100 μM/48 h) | [16] | |||
gastric | BGC-823 (>100 μM/48 h) | [16] | |||
gastric | MGC-803 (>100 μM/48 h) | [16] | |||
cervical | Hela (>100 μM/48 h) | [16] | |||
3 | 17-hydroxyjolkinolide B | ent-abietane | liver | HepG-2 (42.13 μM/48 h) | [16] |
breast | MCF-7 (25.33 μM/48 h) | [16] | |||
gastric | SGC-7901 (44.34 μM/48 h) | [16] | |||
gastric | BGC-823 (48.12 μM/48 h) | [16] | |||
gastric | MGC-803 (43.89 μM/48 h) | [16] | |||
cervical | Hela (35.11 μM/48 h) | [16] | |||
lung | H460 | [16] | |||
ovary | Skov3 | [25] | |||
colo | Colo205 | [25] | |||
breast | MDA-MB-453 | [25] | |||
breast | MDA-MB-231 | [25] | |||
breast | MDA_MB-468 | [25] | |||
cervix | Hela | [25] | |||
liver | HepG2 | [25] | |||
blood | Jurkat | [25] | |||
blood | U937 | [25] | |||
blood | THP-1 | [25] | |||
4 | 17-acetoxyjolkinolide B | ent-abietane | blood | U937 (0.74 μM) | [26] |
blood | Jurkat (1.06 μM) | [26] | |||
colon | Colo205 (2.34 μM) | [26] | |||
gastric | HGC (3.64 μM)) | [26] | |||
breast | MCF-7 (8.74 μM)) | [26] | |||
5 | prostratin | tigliane | liver | HepG-2 (11.77 μM/48 h) | [27] |
breast | MCF-7 (17.4 μM/48 h) | [27] | |||
gastric | SGC-7901 (25.4 μM) | [27] | |||
6 | langduin A | daphnane | liver | HepG-2 (35 μM/48 h) | [27] |
breast | MCF-7 (19.4 μM/48 h) | [27] | |||
gastric | SGC-7901 (21.3μM/48 h) | [27] | |||
7 | 13-O-acetylphorbol | tigliane | liver | HepG-2 (32.3 μM/48 h) | [27] |
breast | MCF-7 (18.1 μM/48 h) | [27] | |||
gastric | SGC-7901 (24.91 μM/48 h) | [27] | |||
8 | 12-deoxyphorbol 13-palmitate | tigliane | breast | MCF-7 | [28] |
gastric | BGC823 | [29] | |||
liver | Hep-3B (12.01 μM) | [30] | |||
lung | A549 (9.38 μM) | [30] | |||
9 | ingenol-6,7-epoxy-3-tetradecanoate | ingenane | lung | A549 (3.35 μg/mL/72 h) | [31] |
liver | BEL7402 (13.05 μg/mL/72 h) | [31] | |||
colon | HCT116 (14.62 μg/mL/72 h) | [31] | |||
breast | MDA-MB-231 (14.42 μg/mL/72 h) | [31] | |||
10 | ingenol-3-myristinate | ingenane | lung | A549 (2.85 μg/mL/72 h) | [31] |
liver | BEL7402 (15.72 μg/mL/72 h) | [31] | |||
colon | HCT116 (16.05 μg/mL/72 h) | [31] | |||
breast | MDA-MB-231 (18.91μg/mL/72 h) | [31] | |||
11 | ingenol 3-palmitate | ingenane | lung | A549 (2.88 μg/mL/72 h) | [31] |
liver | BEL7402 (25.87 μg/mL/72 h) | [31] | |||
colon | HCT116 (14.38 μg/mL/72 h) | [31] | |||
breast | MDA-MB-231 (22 μg/mL/72 h) | [31] | |||
12 | ent-1β,3β,16β, 17-tetrahydroxyatisane | ent-atisane | breast | MCF-7 (23.21 μM) | [32] |
13 | ent-1β,3α,16β, 17-tetrahydroxyatisane | ent-atisane | breast | MCF-7 (15.42 μM) | [32] |
14 | ent-kaurane-3-oxo-16β, 17-acetonide | ent-kaurane | liver | Hep-3B (8.15 μM) | [30] |
No. | Bioactive Ingredient | Subtype | Ref. |
---|---|---|---|
1 | jolkinolide b | ent-abietane | [14,15] |
10 | ingenol-3-myristinate | ingenane | |
11 | ingenol-3-palmitate | ingenane | |
15 | euphorin E | ent-abietane | |
16 | euphorin H | ent-abietane | |
17 | yuexiandajisu E | ent-abietane | |
18 | ingenol-20-myristinate | ingenane | |
19 | ent-3β-hydroxyatis-16-ene-2,14-dione | ent-atisane | |
20 | 19-O-β-d-glucopyranosyl-ent-atis-16-ene-3,14-dione | ent-atisane | |
21 | euphorin C | ent-rosane | |
22 | ebractenoid C | ent-rosane | |
23 | ebractenoid F | ent-rosane | |
24 | jolkinol A | lathyrane |
Animal Models | Drug Dose | Conclusions | Ref. |
---|---|---|---|
MCF-7 cells xenograft in nude mice | four groups: the negative control group, the jolkinolide B group (40 mg/kg), the 5-Fu group (5 mg/kg), and the jolkinolide B+5-Fu group for 28 days | tumor volume and weight in the 5-Fu, the 5-Fu + jolkinolide B and the jolkinolide B group were greatly reduced, while tumors in the control group reached 1207 mm. However, no significant difference was observed between the JB and the JB+5-Fu group | [17] |
B16F10 cells xenograft in C57BL/6 mice | 10, 20 and 40 mg/kg of jolkinolide B by intragastric administration for 7 days | The tumor growth inhibition rates were 17.3%, 34.6% and 54.4% in JB-treated groups (10, 20 and 40 mg/Kg) | [23] |
BGC823 cells in Female Balb/c nude mice | 12-deoxyphorbol 13-palmitate (40 mg/kg) was administered intraperitoneally every three days for two months | tumor growth was significantly suppressed in the 40 mg/mL group compared to the control group | [29] |
No. | Bioactive Ingredient | Type of Cancer | Cell Lines | Mechanisms of Action | Ref. |
---|---|---|---|---|---|
1 | jolkinolide B | breast | MDA-MB-231 | suppression of the PI3K/Akt signaling pathway | [18] |
human leukemic | U937 | suppression of PI3K/Akt and XIAP pathways. cIAP1/2 ↓, Survivin ↓ XIAP ↓ expression Smac ↑ expression activation of caspase-3 and -9. | [19] | ||
HL-60 THP-1 | suppression of the JAK2/STAT3 signaling pathway ↓ JAK2/STAT3 and bcl-2 expression ↑ Bax and cytosolic cytochrome c triggering of caspase-3, -8 and-9 activation | [21] | |||
mouse melanoma | B16F10 | inhibition of glycolysis ↓ mRNA expression of glucose transporter genes (Glut1, Glut3 and Glut4) and glycolysis-related kinase gene(Hk2 and Ldha) ↑ ROS level decreased the potential of mitochondrial membrane | [23] | ||
3 | 17-hydroxyjolkinolide B | Liver Breast breast | HepG2 MDA-MB-231 MDA_MB-468 | inhibit STAT3 activation by direct inhibition of JAK kinase activity through covalent crosslinking of the JAKs | [25] |
4 | 17-acetoxyjolkinolide B | Liver Cervical lung | HepG2 Hela A549 | a inhibitor of IKK inhibit tumor NF-KB activation | [26] |
8 | 12-deoxyphorbol 13-palmitate | gastric | BGC823 | activation of caspase-3 and -9. | [29] |
No | Bioactive Ingredient | Type of Cancer | Cell Lines | Effects of Diterpenoids on Cell Cycle | Ref. |
---|---|---|---|---|---|
1 | jolkinolide B | human leukemic | K562 | Cell cycle arrest at G1 | [20] |
prostate | LNCap | Cell cycle arrest at G1 | [24] | ||
8 | 12-deoxyphorbol 13-palmitate | gastric | BGC823 | cell cycle arrest at G2-M checkpoint ↓ cdc2/cyclin B, cyclin A and p-chk1 protein expression | [29] |
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Jian, B.; Zhang, H.; Han, C.; Liu, J. Anti-Cancer Activities of Diterpenoids Derived from Euphorbia fischeriana Steud. Molecules 2018, 23, 387. https://doi.org/10.3390/molecules23020387
Jian B, Zhang H, Han C, Liu J. Anti-Cancer Activities of Diterpenoids Derived from Euphorbia fischeriana Steud. Molecules. 2018; 23(2):387. https://doi.org/10.3390/molecules23020387
Chicago/Turabian StyleJian, Baiyu, Hao Zhang, Cuicui Han, and Jicheng Liu. 2018. "Anti-Cancer Activities of Diterpenoids Derived from Euphorbia fischeriana Steud" Molecules 23, no. 2: 387. https://doi.org/10.3390/molecules23020387