Holmes William F, Soprano Dianne Robert, Soprano Kenneth J
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
J Cell Physiol. 2004 Jun;199(3):317-29. doi: 10.1002/jcp.10338.
Apoptosis is also known as programmed cell death. Apoptosis plays an essential role in maintaining normal tissue and cell physiology in multicellular organisms. Clearance of aberrant or pre-cancerous cells occurs through the induction of apoptosis. It has been reported that many tumors and tumor cell lines have dysfunctional apoptosis signaling, causing these tumors to escape immune monitoring and internal cellular control mechanisms. One potential cause of this dysfunctional apoptosis is the tumor suppressor p53, an important regulator of growth arrest and apoptosis that is mutated in over 50% of all cancers. Retinoids have great potential in the areas of cancer therapy and chemoprevention. While some tumor cells are sensitive to the growth inhibitory effects of natural retinoids such as all-trans-retinoic acid (ATRA), many ovarian tumor cells are not. 6-[3-(1-Admantyl)]-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and fenretinide N-[4-hydroxyphenyl] retinamide (4-HPR) are conformationally restricted synthetic retinoids that induce growth arrest and apoptosis in both ATRA-sensitive and ATRA-resistant ovarian tumor cell lines. Recently, we have identified the molecular pathways of apoptosis induced by treatment of ovarian carcinoma cells with mutated p53 by CD437 and 4-HPR.
细胞凋亡也被称为程序性细胞死亡。在多细胞生物中，细胞凋亡在维持正常组织和细胞生理方面起着至关重要的作用。通过诱导细胞凋亡可清除异常或癌前细胞。据报道，许多肿瘤和肿瘤细胞系具有功能失调的凋亡信号，导致这些肿瘤逃避免疫监测和细胞内控制机制。这种凋亡功能失调的一个潜在原因是肿瘤抑制因子p53，它是生长停滞和细胞凋亡的重要调节因子，在超过50%的所有癌症中发生突变。维甲酸在癌症治疗和化学预防领域具有巨大潜力。虽然一些肿瘤细胞对全反式维甲酸（ATRA）等天然维甲酸的生长抑制作用敏感，但许多卵巢肿瘤细胞并不敏感。6-[3-(1-金刚烷基)]-4-羟基苯基]-2-萘羧酸（CD437）和芬维A胺N-[4-羟基苯基]维甲酰胺（4-HPR）是构象受限的合成维甲酸，它们在ATRA敏感和ATRA耐药的卵巢肿瘤细胞系中均能诱导生长停滞和细胞凋亡。最近，我们已经确定了用CD437和4-HPR处理突变型p53的卵巢癌细胞所诱导的细胞凋亡分子途径。
