Analogs of the novel phytohormone, strigolactone, trigger apoptosis and synergize with PARP inhibitors by inducing DNA damage and inhibiting DNA repair.

Strigolactones are a novel class of plant hormones produced in roots that regulate shoot and root development. We previously reported that strigolactone analogs (SLs) induce G2/M cell cycle arrest and apoptosis in a variety of human cancer cells and inhibit tumor growth of human breast cancer xenografts in mice. SLs had no significant influences on non-transformed cells.

Strigolactone analogs act as new anti-cancer agents in inhibition of breast cancer in xenograft model.

Strigolactones (SLs) are a novel class of plant hormones. Previously, we found that analogs of SLs induce growth arrest and apoptosis in breast cancer cell lines. These compounds also inhibited the growth of breast cancer stem cell enriched-mammospheres with increased potency.

Cooperation between BRCA1 and vitamin D is critical for histone acetylation of the p21waf1 promoter and growth inhibition of breast cancer cells and cancer stem-like cells.

Carriers of germline mutations in the BRCA1 gene have a significant increased lifetime risk for being diagnosed with breast cancer. The incomplete penetrance of BRCA1 suggests that environmental and/or genetic factors modify the risk and incidence among mutation carriers. Nutrition and particular micronutrients play a central role in modifying the phenotypic expression of a given genotype by regulating chromatin structure and gene expression.

Strigolactone analogues induce apoptosis through activation of p38 and the stress response pathway in cancer cell lines and in conditionally reprogrammed primary prostate cancer cells.

Strigolactones are a novel class of plant hormones produced in roots and regulate shoot and root development. We have previously shown that synthetic strigolactone analogues potently inhibit growth of breast cancer cells and breast cancer stem cells. Here we show that strigolactone analogues inhibit the growth and survival of an array of cancer-derived cell lines representing solid and non-solid cancer cells including: prostate, colon, lung, melanoma, osteosarcoma and leukemic cell lines, while normal cells were minimally affected.

BRCA1-dependent Chk1 phosphorylation triggers partial chromatin disassociation of phosphorylated Chk1 and facilitates S-phase cell cycle arrest.

Chk1 phosphorylation by the PI3-like kinases ATR and ATM is critical for its activation and its role in prevention of premature mitotic entry in response to DNA damage or stalled replication. The breast and ovarian tumor suppressor, BRCA1, is among several checkpoint mediators that are required for Chk1 activation by ATM and ATR. Previously we showed that BRCA1 is necessary for Chk1 phosphorylation and activation following ionizing radiation.

Single-nucleotide polymorphisms in the p53 pathway genes modify cancer risk in BRCA1 and BRCA2 carriers of Jewish-Ashkenazi descent.

Germline mutations in the BRCA1 and BRCA2 genes are associated with a significantly increased lifetime risk for developing breast and/or ovarian cancer. However, incomplete penetrance and substantial variability in age of disease onset among carriers of the same mutation suggests the involvement of additional modifier genes and/or environmental factors. Somatic inactivating mutations in the p53 gene and genes of the p53 pathway often accompany BRCA1/2-associated tumors.

MDM2 SNP309 accelerates breast and ovarian carcinogenesis in BRCA1 and BRCA2 carriers of Jewish-Ashkenazi descent.

A functional single nucleotide polymorphism in the promoter of the MDM2 gene, SNP309 (T>G), was recently found to accelerate tumorigenesis in early onset cancer cases. The SNP309 G-allele, introduces an SP1 site in the MDM2 promoter, resulting in enhanced MDM2 expression and activity. Thus, the G-allele of MDM2 SNP309 may represent a cancer predisposing allele.

Elevated insulin-like growth factor-I receptor (IGF-IR) levels in primary breast tumors associated with BRCA1 mutations.

The insulin-like growth factors (IGFs) play a pivotal role in breast cancer. Inherited predisposition to breast and ovarian cancer is associated with germline BRCA1/BRCA2 mutations. To evaluate the impact of BRCA1 mutations on IGF-IR gene expression, we performed an immunohistochemical analysis of IGF-IR in primary breast tumors from BRCA1 mutation carriers and non-carriers.

Estrogen receptor regulates insulin-like growth factor-I receptor gene expression in breast tumor cells: involvement of transcription factor Sp1.

The insulin-like growth factors, IGF-I and IGF-II are a family of mitogenic polypeptides with important roles in growth and differentiation. The biological actions of the IGFs are mediated by the IGF-I receptor (IGF-IR), a cell-surface tyrosine kinase, whose activation by serum IGF-I seems to be a key step in breast cancer initiation. Evidence accumulated indicates that estrogens stimulate the expression and activity of IGF axis components.

BRCA1 at the crossroad of multiple cellular pathways: approaches for therapeutic interventions.

Approximately 10% of the cases of breast cancer and invasive ovarian cancer are hereditary, occurring predominantly in women with germ-line mutations in the BRCA1 or BRCA2 genes. Low expression of these genes in sporadic tumors extends their significance to sporadic breast and ovarian cancers as well. For over a decade since its identification, extensive research has been directed toward understanding the function of the breast and ovarian tumor suppressor gene BRCA1.

BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage.

The breast cancer tumor-suppressor gene, BRCA1, encodes a protein with a BRCT domain-a motif that is found in many proteins that are implicated in DNA damage response and in genome stability. Phosphorylation of BRCA1 by the DNA damage-response proteins ATM, ATR and hCds1/Chk2 changes in response to DNA damage and at replication-block checkpoints. Although cells that lack BRCA1 have an abnormal response to DNA damage, the exact role of BRCA1 in this process has remained unclear.