Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, Ulm D-89081, Germany.
J Nat Prod. 2011 Aug 26;74(8):1731-6. doi: 10.1021/np200161a. Epub 2011 Jul 29.
Mastic, a resinous exudate from Pistacia lentiscus, has been reported to exhibit selective cytotoxicity against different cancer cell lines. There are, however, no data published correlating distinct mastic-derived compounds with the postulated cytotoxic activity. A polypodane-type bicyclic triterpenoid, (8R)-3β,8-dihydroxypolypoda-13E,17E,21-triene (1), was isolated from P. lentiscus oleogum resin. In androgen-independent PC-3 prostate cancer cells, 1 potently inhibited the expression of cyclins D1 and E, but had no effect on the expression of the cyclin kinase inhibitor p21(Waf1/Cip1). Inhibition of the expression of cell cycle-regulating cyclins resulted in cell cycle arrest in the G₀/G₁ phase, reduction in the number of cells in the S phase, and the triggering of apoptosis, as detected by increased expression of phosphatidylserine on the cell surface and by formation of DNA laddering. In addition, 1 suppressed the formation of prostate cancer colonies in soft agar and inhibited proliferation, angiogenesis, and the growth of prostate tumors xenografted onto chick chorioallantoic membranes without overt systemic toxicity. Taken together, these data show that 1 triggers apoptosis in chemoresistant, androgen-independent human prostate cancer cells in vitro and in vivo. Thus, 1 may serve as a lead compound for targeting so far incurable androgen-insensitive prostate cancers.
乳香，一种从乳香黄连木中渗出的树脂，据报道对不同的癌细胞系具有选择性细胞毒性。然而，目前尚无数据表明乳香中的特定化合物与假设的细胞毒性活性有关。一种多足烷型双环三萜类化合物，（8R）-3β,8-二羟基多足烷-13E,17E,21-三烯（1），从乳香黄连木油树脂中分离得到。在雄激素非依赖性 PC-3 前列腺癌细胞中，1 强烈抑制细胞周期蛋白 D1 和 E 的表达，但对细胞周期蛋白激酶抑制剂 p21（Waf1/Cip1）的表达没有影响。细胞周期调节细胞周期蛋白的表达抑制导致细胞周期停滞在 G₀/G₁ 期，S 期细胞数量减少，并触发细胞凋亡，如细胞膜上磷脂酰丝氨酸的表达增加和 DNA 梯状形成所检测到的。此外，1 抑制软琼脂中前列腺癌细胞集落的形成，并抑制增殖、血管生成和植入鸡胚绒毛尿囊膜上的前列腺肿瘤的生长，而没有明显的全身毒性。综上所述，这些数据表明，1 在体外和体内触发化学耐药性、雄激素非依赖性人前列腺癌细胞的细胞凋亡。因此，1 可能成为针对迄今无法治愈的雄激素不敏感前列腺癌的潜在药物。
