Orally available and efficacious α4β1/α4β7 integrin inhibitors.

A series of potent α4β1/α4β7 integrin inhibitors is reported, including an inhibitor 12d with remarkable oral exposure and efficacy in rat models of rheumatoid arthritis and Crohn's disease.

Selective concomitant inhibition of mTORC1 and mTORC2 activity in estrogen receptor negative breast cancer cells by BN107 and oleanolic acid.

Hormonal, targeted and chemotherapeutic strategies largely depend on the expression of their cognate receptors and are often accompanied by intolerable toxicities. Effective and less toxic therapies for estrogen receptor negative (ER-) breast cancers are urgently needed. Here, we present the potential molecular mechanisms mediating the selective pro-apoptotic effect induced by BN107 and its principle terpene, oleanolic acid (OA), on ER- breast cancer cells.

Timosaponin AIII is preferentially cytotoxic to tumor cells through inhibition of mTOR and induction of ER stress.

The aqueous extract of Anemarrhena asphodeloides (BN108) induces apoptosis in various cancer cell lines but is significantly less cytotoxic in non-transformed cells. Chemical fractionation of BN108 showed that its cytotoxicity is associated with timosaponins, steroidal saponins of coprostane type. Timosaponin BII (TBII) is a major saponin in BN108, but it shows little cytotoxicity.

Molecular mechanisms underlying selective cytotoxic activity of BZL101, an extract of Scutellaria barbata, towards breast cancer cells.

We studied the mechanism of the cytotoxic activity of BZL101, an aqueous extract from the herb Scutellaria barbata D. Don, which is currently in phase II clinical trial in patients with advanced breast cancer. The phase I trial showed favorable toxicity profile and promising efficacy.

Phase I trial and antitumor effects of BZL101 for patients with advanced breast cancer.

Background: Botanical therapies are often used by breast cancer patients yet few clinical trials have evaluated their safety and efficacy. We studied mechanisms of activity and performed a phase I clinical trial in patients with advanced breast cancer to evaluate BZL101, an aqueous extract from Scutellaria barbata.

Methods: Preclinical studies were conducted in vitro to characterize cell death induced by BZL101.

Breast cancer growth prevention by statins.

Statins are cholesterol-lowering drugs with pleiotropic activities including inhibition of isoprenylation reactions and reduction of signals driving cell proliferation and survival responses. The objectives of this study were to examine the effects of statins on breast cancer cells, both in vitro and in vivo, and to begin to determine their mechanism of action. We evaluated the effects of statins on breast cancer cell growth, phosphoprotein signaling intermediates, survival/apoptosis regulators, cell cycle regulators, and activated transcription factors.

In vitro anticancer activity of twelve Chinese medicinal herbs.

Aqueous extracts of 12 Chinese medicinal herbs, Anemarrhena asphodeloides, Artemisia argyi, Commiphora myrrha, Duchesnea indica, Gleditsia sinensis, Ligustrum lucidum, Rheum palmatum, Rubia cordifolia, Salvia chinensis, Scutellaria barbata, Uncaria rhychophylla and Vaccaria segetalis were evaluated for their antiproliferative activity on eight cancer cell lines as well as on normal human mammary epithelial cells. Five human and three murine cancer cell lines representing different tissues (breast, lung, pancreas and prostate) were used. All the crude aqueous extracts demonstrated growth inhibitory activity on some or all of the cancer cell lines, but only two showed activity against the normal mammary epithelial cells.

Reduction of MTT by aqueous herbal extracts in the absence of cells.

The tetrazolium salt 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) is used to determine cell viability in assays of cell proliferation and cytotoxicity. MTT is reduced in metabolically active cells to yield an insoluble purple formazon product. However, in the present study, we demonstrate that some botanical extracts can reduce MTT in the absence of living cells.

Antiproliferative activity of Chinese medicinal herbs on breast cancer cells in vitro.

Chinese medicinal herbs are traditionally used to prevent and treat a variety of diseases, including cancer. These herbal preparations are purported to have many biological effects including direct antiproliferative effects on cancer cells, anti-mutagenic activity, and stimulatory or suppressive effects on immune responses. The present study investigates the effects of aqueous extracts from seventy-one Chinese medicinal herbs on the growth of five breast cancer cell lines (SK-BR-3, MCF7, MDA-MB-231, BT-474 and MCNeuA).