Fox F E, Niu Z, Tobia A, Rook A H
Department of Dermatology, University of Pennsylvania, Philadelphia 19104, USA.
J Invest Dermatol. 1998 Aug;111(2):327-32. doi: 10.1046/j.1523-1747.1998.00278.x.
Hypericin is a photodynamic compound activated by either visible (400-700 nm) or UVA (320-400 nm) light, and has been shown to inhibit the growth of a variety of neoplastic cell types. In this study, hypericin was found to inhibit proliferative responses of malignant T cells derived from the blood of patients with cutaneous T cell lymphoma. Control cells included peripheral blood mononuclear cells (PBMC) from normal volunteers or Epstein-Barr virus-transformed lymphocytes. Cells from each of these populations were incubated with serial dilutions of hypericin or 8-methoxypsoralen and then stimulated with the mitogen ConA (10 microg per ml). Cultures were prepared in the dark to minimize photoactivation of the hypericin. Proliferation was measured by [3H]thymidine labeling after 72 h. Hypericin, photoactivated with 1.1-3.3 J white light per cm2, inhibited cellular proliferation of malignant T cells with IC50 values from 0.34 to 0.53 microM, normal PBMC with IC50 values of 0.11-0.76 microM, and Epstein-Barr virus-transformed cells with IC50 values of 0.75-3.2 microM. UVA-photoactivated hypericin (0.5-2.0 J per cm2) could also inhibit proliferation with IC50 values of 0.57-1.8 microM, 0.7-4.6 microM, and 2.0-3.7 microM for malignant, normal, or Epstein-Barr virus-transformed cells, respectively. Hypericin, photoactivated with either UVA or white light, could induce near complete apoptosis (94%) in malignant cutaneous T cell lymphoma T cells, whereas lower levels of apoptosis (37-88%) were induced in normal PBMC. These data indicate that hypericin inhibits mitogen-induced proliferation of malignant T cells from patients with cutaneous T cell lymphoma, PBMC from normal individuals, as well as Epstein-Barr virus-transformed lymphocytes, and that inhibition of cell proliferation is dependent on the concentration of hypericin used and the dose of light required to photoactivate the compound. Induction of apoptosis is, in part, one mechanism by which photoactivated hypericin inhibits malignant T cell proliferation.
金丝桃素是一种光动力化合物，可被可见光（400 - 700纳米）或紫外线A（320 - 400纳米）激活，并且已显示出能抑制多种肿瘤细胞类型的生长。在本研究中，发现金丝桃素可抑制源自皮肤T细胞淋巴瘤患者血液中的恶性T细胞的增殖反应。对照细胞包括来自正常志愿者的外周血单核细胞（PBMC）或爱泼斯坦 - 巴尔病毒转化的淋巴细胞。将来自这些群体的细胞与金丝桃素或8 - 甲氧基补骨脂素的系列稀释液孵育，然后用丝裂原刀豆蛋白A（每毫升10微克）刺激。培养物在黑暗中制备，以尽量减少金丝桃素的光激活。72小时后通过[3H]胸苷标记测量增殖。用每平方厘米1.1 - 3.3焦耳白光光激活的金丝桃素，抑制恶性T细胞的细胞增殖，IC50值为0.34至0.53微摩尔，正常PBMC的IC50值为0.11 - 0.76微摩尔，爱泼斯坦 - 巴尔病毒转化细胞的IC50值为0.75 - 3.2微摩尔。紫外线A光激活的金丝桃素（每平方厘米0.5 - 2.0焦耳）也可抑制增殖，恶性、正常或爱泼斯坦 - 巴尔病毒转化细胞的IC50值分别为0.57 - 1.8微摩尔、0.7 - 4.6微摩尔和2.0 - 3.7微摩尔。用紫外线A或白光光激活的金丝桃素可在恶性皮肤T细胞淋巴瘤T细胞中诱导近乎完全的凋亡（94%），而在正常PBMC中诱导较低水平的凋亡（37 - 88%）。这些数据表明，金丝桃素抑制皮肤T细胞淋巴瘤患者的恶性T细胞、正常个体的PBMC以及爱泼斯坦 - 巴尔病毒转化淋巴细胞的丝裂原诱导的增殖，并且细胞增殖的抑制取决于所用金丝桃素的浓度和光激活该化合物所需的光剂量。凋亡的诱导部分是光激活的金丝桃素抑制恶性T细胞增殖的一种机制。
