Rieber M, Strasberg Rieber M
IVIC, Tumor Cell Biology Laboratory, Caracas, Venezuela.
DNA Cell Biol. 1998 May;17(5):399-406. doi: 10.1089/dna.1998.17.399.
Because betulinic acid was recently described as a melanoma-specific inducer of apoptosis, we investigated whether this agent was comparably effective against metastatic tumors and those in which metastatic ability and 92-kD gelatinase activity had been decreased by introduction of a normal chromosome 6. Human metastatic C8161 melanoma cells showed greater DNA fragmentation and growth arrest and earlier loss of viability in response to betulinic acid than their non-metastatic C8161/neo 6.3 counterpart. These effects involved induction of p53 without activation of p21WAF1 and were synergized by bromodeoxyuridine in metastatic Mel Juso, with no comparable responses in non-metastatic Mel Juso/neo 6 cells. Our data suggest that betulinic acid exerts its inhibitory effect partly by increasing p53 without a comparable effect on p21WAF1.
由于桦木酸最近被描述为黑色素瘤特异性凋亡诱导剂，我们研究了该药物对转移性肿瘤以及通过导入正常6号染色体使转移能力和92-kD明胶酶活性降低的肿瘤是否具有同等效力。与非转移性C8161/neo 6.3对应细胞相比，人转移性C8161黑色素瘤细胞对桦木酸的反应表现出更大程度的DNA片段化和生长停滞，以及更早的活力丧失。这些效应涉及p53的诱导而未激活p21WAF1，并且在转移性Mel Juso细胞中与溴脱氧尿苷协同作用，而在非转移性Mel Juso/neo 6细胞中没有类似反应。我们的数据表明，桦木酸部分通过增加p53发挥其抑制作用，而对p21WAF1没有类似影响。
