Hergenhahn M, Kusumoto S, Hecker E
J Cancer Res Clin Oncol. 1984;108(1):98-109. doi: 10.1007/BF00390980.
The irritant and tumor-promoting principles were isolated from the latex of Euphorbia resinifera Berg. and from the resin derived from latex (euphorbium), which is commercially available as a drug. The irritant Euphorbia factors RL 5 (mixture), RL 6, RL 7, RL 8, and RL 10 were identified as tigliane-type 12-deoxyphorbol esters each bearing, in the 13 position, either long-chain, partially methyl-substituted acyl residues (10-16 carbon atoms) or short-chain acyl residues (4 or 5 carbon atoms) or a (substituted) phenylacetyl group with a 20-acetoxy group. Euphorbia factors RL 15 (mixture), RL 16, RL 17, RL 18, and RL 21 are the corresponding 20-deacetylated derivatives thereof. The irritant Euphorbia factors RL 11, RL 12, RL 22, RL 23 were characterized as esters of the tigliane type 12-deoxy-16-hydroxyphorbol, i.e., 13-0-phenylacetyl-16-0-benzoyl-12-deoxy16-hydroxyphorbol-20- acetate (RL 11) and 13, 16-0-phenylacetyl, tigloyl-12-deoxy-16-hydroxy-phorbol-20-acetate (RL 12), RL 22 and RL 23 representing the respective 20-deacetylated derivatives. A mixture of irritant factors, RL 13, was shown to represent long-chain 3-esters of ingenane-type ingenol with similar acyl residues (10-16 carbon atoms, partially methyl-substituted) to RL 5 (RL 15) above. A further group of E. resinifera factors was of the daphnane type: RL 9 was identified as the extremely irritant 9,13,14-orthophenylacetate of resiniferonol-20-(4-hydroxy-3-methoxy)phenylacetate (Resiniferatoxin), RL 14 as the corresponding 9,13,14-orthophenylacetate of resiniferonol, and RL 20 as 14-0-phenylacetylresiniferonol-20-(4-hydroxy-3-methoxy)-phenylacet ate (Proresiniferatoxin). The irritant factors specified below were accompanied by nonirritant esters of the tigliane type 12,20-dideoxyphorbol, i.e., RL 1 and RL 2, and of the lathyrane type ingol, i.e., RL 3 and RL 4. In tumor promotion experiments the mixture of homologous irritant factors RL 13 was equipotent with the standard tumor promoter TPA, but at 10 times the dose of TPA. Several others of the irritant factors had low activity as tumor promotors, but of the few tumors obtained in these experiments a high percentage was malignant. The very high irritant activity of the latex may be ascribed to resiniferatoxin (RL 9), representing a new class of rapidly acting skin irritants. No promoting activity was detected on administration of the highly irritant resiniferatoxin.
刺激性和促肿瘤成分是从绿玉树（Euphorbia resinifera Berg.）的乳汁以及从乳汁衍生的树脂（大戟脂）中分离得到的，大戟脂作为一种药物在市场上有售。刺激性大戟因子RL 5（混合物）、RL 6、RL 7、RL 8和RL 10被鉴定为替告皂苷元型12 - 脱氧佛波醇酯，在13位上分别带有长链、部分甲基取代的酰基残基（10 - 16个碳原子）或短链酰基残基（4或5个碳原子）或带有20 - 乙酰氧基的（取代）苯乙酰基。大戟因子RL 15（混合物）、RL 16、RL 17、RL 18和RL 21是其相应的20 - 脱乙酰化衍生物。刺激性大戟因子RL 11、RL 12、RL 22、RL 23被表征为替告皂苷元型12 - 脱氧 - 16 - 羟基佛波醇的酯，即13 - O - 苯乙酰基 - 16 - O - 苯甲酰基 - 12 - 脱氧 - 16 - 羟基佛波醇 - 20 - 乙酸酯（RL 11）和13,16 - O - 苯乙酰基，惕各酰基 - 12 - 脱氧 - 16 - 羟基佛波醇 - 20 - 乙酸酯（RL 12），RL 22和RL 23分别代表相应的20 - 脱乙酰化衍生物。刺激性因子混合物RL 13被证明是具有与上述RL 5（RL 15）相似酰基残基（10 - 16个碳原子，部分甲基取代）的映南柯烷型大戟醇的长链3 - 酯。绿玉树的另一组因子属于瑞香烷型：RL 9被鉴定为树脂大戟醇 - 20 -（4 - 羟基 - 3 - 甲氧基）苯乙酸酯（树脂毒素）的极具刺激性的9,13,14 - 原苯乙酸酯，RL 14为树脂大戟醇相应的9,13,14 - 原苯乙酸酯，RL 20为14 - O - 苯乙酰基树脂大戟醇 - 20 -（4 - 羟基 - 3 - 甲氧基）苯乙酸酯（原树脂毒素）。以下指定的刺激性因子伴有替告皂苷元型12,20 - 二脱氧佛波醇的无刺激性酯，即RL 1和RL 2，以及拉替兰型大戟醇的无刺激性酯，即RL 3和RL 4。在肿瘤促进实验中，同源刺激性因子RL 13的混合物与标准肿瘤促进剂TPA等效，但剂量是TPA的10倍。其他几种刺激性因子作为肿瘤促进剂的活性较低，但在这些实验中获得的少数肿瘤中，高比例是恶性的。乳汁的极高刺激性活性可能归因于树脂毒素（RL 9），它代表了一类新型的快速起效的皮肤刺激物。给予极具刺激性的树脂毒素后未检测到促进活性。
