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

Rugo, Hope S.; Shtivelman, Emma; Perez, Alejandra; Vogel, Charles L.; Franco, Sandra; Chiu, Elizabeth; Melisko, Michelle; Tagliaferri, Mary; Cohen, Isaac; Shoemaker, Mark; Tran, Zung Vu; Tripathy, Debasish

doi:10.1007/s10549-006-9430-6

Cited by 90 publications

(89 citation statements)

References 9 publications

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“…completed Phase Ia and Ib clinical trials for treatment of metastasized breast cancer with encouraging results (Rugo et al, 2007;Perez et al, 2010). Along with its anticancer properties, S.…”

Section: Figurementioning

confidence: 99%

“…The traditional method of extracting TCM herbs by simmering in water was followed when making extracts of S. barbata for both Ia and Ib phases of BZL101's clinical trials (Rugo et al, 2007;Perez et al, 2010). However, during Phase Ib, a modified formulation using freeze-dried powdered drug with sweeteners and taste-masking excipients was introduced to increase patient adherence.…”

Section: Comparison Of S Barbata Clinical Trials With Traditional Tcmentioning

confidence: 99%

“…It is unclear if freeze-drying or the addition of other excipients would change efficacy but neither are traditionally used by TCM practitioners. However, one major benefit of the modernization of dosage form involves increased patient compliance since it was noted that during Phase Ia trials some patients discontinued therapy due to bitter taste of the drug when prepared using traditional methods (Rugo et al, 2007). In the Phase Ib trial, after implementing the new dosage form, patient compliance increased and no patients dropped out of study due to drug taste (Perez et al, 2010).…”

Section: Comparison Of S Barbata Clinical Trials With Traditional Tcmentioning

confidence: 99%

“…Contrary to this practice, the two clinical trials of BZL101 involved daily dosing that was only discontinued due to patient preference, intolerable side effects, or progression of disease (Rugo et al, 2007;Perez et al, 2009). The longest continued use of S. barbata was 449 days by one patient during the Phase Ib trial (Perez et al, 2010).…”

Section: Comparison Of S Barbata Clinical Trials With Traditional Tcmentioning

confidence: 99%

“…Western research has recently turned its attention to S. barbata as a possible source of anticancer compounds. An aqueous extract of the aerial parts of S. barbata named Bezielle (BZL101) was developed by Bionovo, a California-based biotechnology company, and completed Phase I clinical trials in the United States with favorable results (Rugo et al, 2007;Perez et al, 2010). Unfortunately, the developmental of this S. barbata-based medicine has been halted due to insufficient funding (Bionovo, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Current therapeutic role and medicinal potential of Scutellaria barbata in Traditional Chinese Medicine and Western research

Tao

Balunas

2016

Journal of Ethnopharmacology

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Ethnopharmacological relevance: Scutellaria barbata is a common herb in Traditional ChineseMedicine (TCM) most often used to treat cancer. S. barbata has been found to exhibit efficacy both in vitro and in vivo on a variety of cancer types. Similarly encouraging results have been shown in patients with metastatic breast cancer from Phase Ia and Ib clinical trials. This study aims to elucidate the current use of S. barbata by TCM practitioners and in current Western research. Materials and Methods:Semi-structured interviews were conducted with fifteen TCM practitioners in Beijing and Nanjing, China to understand their clinical use of S. barbata.Practitioners were also asked to comment on the future development of TCM using Western research methods and the potential for integration of the two types of medicine in clinical therapy. Statistical analyses were conducted to compare use of S. barbata by disease and in conjunction with other herbs.Results: Current Western research related to S. barbata is focused on cancer treatment, which corresponds to the most common use of S. barbata by TCM practitioners. Other common uses that practitioners reported included infection and inflammation, for which Beijing practitioners reported use of S. barbata more often than Nanjing practitioners (p < 0.05). Hedyotis diffusa was found to be the most commonly cited herb to pair with S. barbata for cancer treatment (p < 0.05).When compared to Western clinical trials of BZL101, an S. barbata extract, TCM practitioners reported using smaller doses of S. barbata in shorter durations, in combination with numerous other herbs with the goal to potentiate therapeutic efficacy and mitigate side effects. In addition, TCM practitioners repeatedly emphasized symptom differentiating as the key to achieving maximum therapeutic potential of S. barbata, a factor typically overlooked in Western research.

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Section: Figurementioning

confidence: 99%

Section: Comparison Of S Barbata Clinical Trials With Traditional Tcmentioning

confidence: 99%

Section: Comparison Of S Barbata Clinical Trials With Traditional Tcmentioning

confidence: 99%

Section: Comparison Of S Barbata Clinical Trials With Traditional Tcmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Current therapeutic role and medicinal potential of Scutellaria barbata in Traditional Chinese Medicine and Western research

Tao

Balunas

2016

Journal of Ethnopharmacology

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neo‐Clerodane Diterpenoids from the Aerial Part of Scutellaria barbata

Lee

Shim

2011

Helvetica Chimica Acta

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Three new neo-clerodane diterpenoids, barbatellarines C -E (1 -3), were isolated from the CHCl 3 -soluble fraction of the aerial part of Scutellaria barbata. Their chemical structures were elucidated by detailed analysis of NMR and MS data. Compounds 1 and 2 were C(13) epimers, which was confirmed by an NOE difference experiment and the NOESY spectrum. The relative configuration was determined on the basis of the 1 H-NMR J-value and NOE data, while the absolute configuration of the previously isolated analogue, barbatellarine B (4), as a representative member of the group, was assigned by CD analysis.Introduction. -Scutellaria barbata D. Don (Labiatae) is a perennial herb with native distribution throughout Korea and Southern China. This herb is known in traditional Korean medicine as Banjiryun and has been used as an anti-inflammatory and antitumor agent [1 -3]. Previous investigations of this plant have revealed the presence of over thirty flavonoids, more than ten neo-clerodane-type diterpenoids, triterpenoids, and sterol glucosides, some of which have exhibited interesting biological activities [4 -12]. In our previous phytochemical studies of S. barbata, we reported on the isolation of two neo-clerodane diterpenoid alkaloids, barbatellarines A and B, together with known compounds (neo-clerodane ¼ (1S,2R,4aS,5R,8aS)-decahydro-1,2,4a,5-tetramethyl-1-[(3R)-3-methylpentyl]naphthalene) [13].As part of our ongoing search for new neo-clerodane diterpenoids from the aerial part of S. barbata distributed in a Korean market, we have further isolated three new neo-clerodane type diterpenoids, named barbatellarines C -E 1 ) (1 -3; Fig. 1). In this report, we describe the isolation and structural elucidation of three new compounds based on 1D-and 2D-NMR data.

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Bezielle (BZL101)‐induced oxidative stress damage followed by redistribution of metabolic fluxes in breast cancer cells: A combined proteomic and metabolomic study

Klawitter

Gurshtein

et al. 2011

Intl Journal of Cancer

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Bezielle (BZL101)-induced oxidative stress damage followed by redistribution of metabolic fluxes in breast cancer cells: a combined proteomic and metabolomic study Bezielle is an orally administered aqueous extract of Scutellaria barbata for treatment of advanced and metastatic breast cancer. Phase I trials showed promising tolerability and efficacy. In our study, we used a combined proteomic-metabolomic approach to investigate the molecular pathways affected by Bezielle in ER-positive BT474 and ER-negative SKBR3 cell lines. In both, Bezielle inhibited cell proliferation, induced cell death and G2 cycle arrest by regulating the mediator proteins Jab1, p27 Kip1 and p21 Cip1 . In addition, it stimulated reactive oxygen species production, hyperactivation of PARP and inhibition of glycolysis. Bezielle's ability to induce oxidative stress was associated with the changes in expression of redox potential maintaining enzymes: glutathione-and thioredoxin-related proteins and peroxiredoxins. In regards to cell metabolism, decreased expression of a-enolase was associated with a reduction of de novo 13 C-lactate formation. Reduced Krebs cycle activity as evidenced by the reduced expression of a-ketoglutarate dehydrogenase and succinyl-CoA synthetase led to decreased intracellular succinate concentrations. By inhibiting glucose metabolism, cells reacted by lowering the expression of glucose transporters and resulting in decreased intracellular glucose concentration. Decreased expression of fatty acid synthase and reduced concentration of phosphocholine indicated considerable changes in phospholipid metabolism. Ultimately, by inhibiting the major energy-producing pathways, Bezielle caused depletion of ATP and NAD(H). Both cell lines were responsive, thus suggesting that Bezielle has the potential to be effective against ER-negative breast cancers. In conclusion, Bezielle's cytotoxicity toward cancer cells is primarily based on inhibition of metabolic pathways that are preferentially activated in tumor cells thus explaining its specificity for cancer cells.

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

Abstract: BZL 101 inhibits breast cancer cell lines by inducing apoptosis. In a phase I clinical trial, BZL101 was safe and had a favorable toxicity profile. BZL101 demonstrated encouraging clinical activity in this heavily pretreated population.

Cited by 90 publications

References 9 publications

Current therapeutic role and medicinal potential of Scutellaria barbata in Traditional Chinese Medicine and Western research

Current therapeutic role and medicinal potential of Scutellaria barbata in Traditional Chinese Medicine and Western research

neo‐Clerodane Diterpenoids from the Aerial Part of Scutellaria barbata

Bezielle (BZL101)‐induced oxidative stress damage followed by redistribution of metabolic fluxes in breast cancer cells: A combined proteomic and metabolomic study

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