An innovative anti-cancer Chinese herbal formula exhibited multi-targeted efficacies in metastatic breast cancer mouse model.

BACKGROUND: The incidence and mortality of cancer metastasis is high worldwide. Despite of the chemotherapeutic agents, many cancer patients still take traditional Chinese herbal prescriptions as adjuvant treatments. However, most of these herbal formulae/products lack of evidence-based efficacy. Based on our previous investigations on anti-tumor, anti-angiogenic, anti-metastatic, bone protective and immunomodulating activities of various Chinese herbal medicines, four constituent herbs, namely Andrographis paniculata, Acanthopanax senticosus, Camellia sinensis, and Hedyotis diffusa were eventually selected to form an innovative herbal formula. METHODS: The anti-tumor efficacies of the formula were evaluated in metastatic breast cancer mice model. The bone protective and immunomodulatory effects were also assessed after formula treatment. RESULTS: Our results showed that the breast tumor weight as well as lung and liver metastasis in mice could be reduced after herbal formula treatment for 4 weeks. The breast tumor-induced osteolysis in mice was restored by herbal formula treatment, in which the bone volume in treated mice tibia was comparable to that in the non-tumor bearing normal mice. The IL-12 level was augmented and the survival of mice with metastatic breast tumors was prolonged after treatment. Furthermore, combination of herbal formula with chemotherapeutic agent doxorubicin resulted in better anti-tumor efficacy and increased life span in tumor-bearing mice, when compared with doxorubicin alone treatment. CONCLUSIONS: In summary, our innovative Chinese herbal formula was demonstrated to possess anti-tumor, anti-metastatic and bone-protective activities in metastatic breast tumor-bearing mice. The preclinical data generated in this study would lead to the development of evidence-based supplement as adjuvant therapy for metastatic breast cancer.

Gene expression profiling on the molecular action of danshen-gegen formula in a randomized placebo-controlled trial of postmenopausal women with hypercholesterolemia.

The Danshen-Gegen formula (DG) is a traditional Chinese herbal formula which has long been used to treat cardiovascular disease. DG was found to be a cardiovascular tonic in our recent research. However, a comprehensive investigation of the molecular mechanism of DG in cardiovascular disease has not been performed. The aim of this study was to clarify the transcriptional profiling of genes modulated by DG on postmenopausal women by using DNAmicroarray technology. We obtained 29 whole blood samples both from DG-treated and placebo-treated subjects. Blood lipid profile and intima-media thickness (IMT) were measured. Affymetrix GeneChip was used to identify differentially expressed genes (DEGs), followed by validation by the real-time PCR method. The results showed that DG-treated group has a significant improvement in IMT and lipid profile as compared to placebo-treated group. For the genomic study, the DG-treated group has a higher number of DEGs identified as compared to the placebo-treated group. Two important biological processes of "regulation of systemic arterial blood pressure by hormone" and "regulation of smooth muscle proliferation" have been identified by GePS in the DG-treated group. No significant biological process and cellular components were identified in the placebo-treated group. This genomic study on the molecular action of DG in postmenopausal women gathered sufficient molecular targets and pathways to reveal that DG could improve neointima thickening and hypertension.

Photodynamic therapy of Pheophorbide a inhibits the proliferation of human breast tumour via both caspase-dependent and -independent apoptotic pathways in in vitro and in vivo models.

Breast cancer is conventionally treated by surgery and radiotherapy, with adjuvant chemotherapy and hormonotherapy as supplementary treatments. However, such treatments are associated with adverse side effects and drug resistance. In this study, Pheophorbide a (Pa), a photosensitizer isolated from Scutelleria barbata, was analysed for its antiproliferative effect on human breast tumour cells. The IC (inhibitory concentration)(50) of the combined treatment of Pa and photodynamic therapy (Pa-PDT) on human breast tumour MCF-7 cells was 0.5 µm. Mechanistic studies in MCF-7 cells demonstrated that Pa was localized in the mitochondria, and reactive oxygen species were found to be released after Pa-PDT. Apoptosis was the major mechanism responsible for the tumour cell death, and mitochondrial membrane depolarization and cytochrome c release highlighted the role of mitochondria in the apoptotic mechanism. Up-regulation of tumour suppressor protein p53, cleavage of caspase-9 and poly (ADP-ribose) polymerase suggested that the caspase-dependent pathway was induced, while the release of apoptosis-inducing factors demonstrated that the apoptosis was also mediated by the caspase-independent mechanism. In vivo study using the mouse xenograft model showed a significant inhibition of MCF-7 tumour growth by Pa-PDT. Together, the results of this study provide a basis for understanding and developing Pa-PDT as a cure for breast cancer.