BZL101, a phytochemical extract from the<i>Scutellaria barbata</i>plant, disrupts proliferation of human breast and prostate cancer cells through distinct mechanisms dependent on the cancer cell phenotype

Marconett, Crystal N.; Morgenstern, Travis J; Roman, Adrianna K. San; Sundar, S; Singhal, Ankur K.; Firestone, Gary L.

doi:10.4161/cbt.10.4.12424

Cited by 54 publications

(32 citation statements)

References 29 publications

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“…Importantly, BZL101 kills specifically malignant but not normal cells, following a nonclassical apoptotic model with a very limited activation of caspases. Recent works have reported complementary mechanisms related to BZL101-induced PCD (79) and have demonstrated that intraperitoneal injection of BZL101 inhibits tumor growth in mice (80). Importantly, results from the phase I trial, performed in patients with advanced breast cancer, proved an efficient anti-tumor activity of this drug (81).…”

Section: Therapeutic Strategies Targeting Aif-mediated Caspase-indepementioning

confidence: 96%

AIF‐mediated caspase‐independent necroptosis: A new chance for targeted therapeutics

et al. 2011

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SummaryCell death has been initially divided into apoptosis, in which the cell plays an active role, and necrosis, which is considered a passive cell death program. Intense research performed in the last decades has concluded that ''programmed'' cell death (PCD) is a more complex physiological process than initially thought. Indeed, although in most cases the PCD process is achieved via a family of Cys proteases known as caspases, an important number of regulated PCD pathways do not involve this family of proteases. As a consequence, active forms of PCD are initially referred to as caspase-dependent and caspase-independent. More recent data has revealed that there are also active caspase-independent necrotic pathways defined as necroptosis (programmed necrosis). The existence of necroptotic forms of death was corroborated by the discovery of key executioners such as the kinase RIP1 or the mitochondrial protein apoptosis-inducing factor (AIF). AIF is a Janus protein with a redox activity in the mitochondria and a pro-apoptotic function in the nucleus. We have recently described a particular form of AIF-mediated caspase-independent necroptosis that also implicates other molecules such as PARP-1, calpains, Bax, Bcl-2, histone H2AX, and cyclophilin A. From a therapeutic point of view, the unraveling of this new form of PCD poses a question: is it possible to modulate this necroptotic pathway independently of the classical apoptotic paths? Because the answer is yes, a wider understanding of AIF-mediated necroptosis could theoretically pave the way for the development of new drugs that modulate PCD. To this end, we present here an overview of the current knowledge of AIF and AIF-mediated necroptosis. We also summarize the state of the art in some of the most interesting therapeutic strategies that could target AIF or the AIF-mediated necroptotic pathway.

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Section: Therapeutic Strategies Targeting Aif-mediated Caspase-indepementioning

confidence: 96%

AIF‐mediated caspase‐independent necroptosis: A new chance for targeted therapeutics

et al. 2011

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“…TCM, with its relatively high safety and long history of pharmacological applications, has attracted attention in the field of cancer treatment (20,23). SB is a herb used in TCM formulations, where it is considered to have 'heat-clearing and detoxifying' actions, and has many reported applications in cancer treatment (36)(37)(38)(39)(40)(41). Similar to other medicinal herbs, SB is a multi-targeted agent that is considered to exert its therapeutic function holistically (27,31,32,42); thus, it may be a good candidate as an anticancer drug.…”

Section: Discussionmentioning

confidence: 99%

Scutellaria?barbata D. Don inhibits migration and invasion of colorectal cancer cells via suppression of PI3K/AKT and TGF‑β/Smad signaling pathways

et al. 2017

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Abstract. Metastasis is one of the most aberrant behaviors of cancer cells. Patients with cancers, including colorectal cancer (CRC), have a higher risk of tumor recurrence and cancer-related mortality once metastasis is diagnosed. Existing treatment strategies fail to cure cancer mostly due to the onset of metastasis. Therefore, metastasis remains a challenge in cancer treatment. Some complementary and alternative medical therapies using traditional Chinese medicine have been demonstrated to be clinically effective in cancer treatment. Scutellaria barbata D. Don (SB) is a promising medicinal herb. It was previously reported that the ethanol extract of SB (EESB) is able to promote apoptosis, and inhibit cell proliferation and angiogenesis in human colon cancer cells. However, the anticancer effect of SB and the underlying mechanism require further investigation, particularly its role against metastasis. To further elucidate the antimetastatic effect of SB, MTT and Transwell assays were used in the present study to evaluate the effect of EESB on the proliferation, migration and invasion of the CRC cell line HCT-8. In addition, western blot analysis was performed to detect the expression of matrix metalloproteinases (MMPs), cadherins and other metastasis-associated proteins. EESB significantly reduced HCT-8 cell viability and attenuated the migration and invasion ability of HCT-8 cells in a dose-dependent manner. In addition, EESB decreased the expression of MMP-1, MMP-2, MMP-3/10, MMP-9 and MMP-13, and proteins in the phosphoinositide 3-kinase (PI3K)/AKT and transforming growth factor (TGF)-β/Smad pathways, but not the epithelial-mesenchymal transition (EMT)-related factors E-cadherin and N-cadherin. In conclusion, the results suggested that SB inhibits CRC cell metastasis via the suppression of PI3K/AKT and TGF-β/Smad signaling pathways, which may represent a mechanism by which SB exerts an anticancer effect.

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“…Among Chinese traditional medicinal plants, Scutellaria barbata D. Don (SB) has been traditionally used for the treatment of inflammation, such as hepatitis, osteomyelitis, gynecological diseases, due to its antibacterial activity. Recently, SB has gained increasingly attention to its usage as an antitumor herb (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). Similar to other medicinal herbs, SB is considered to be a multi-target agent that exerts therapeutic function in a holistic way.…”

Section: Discussionmentioning

confidence: 99%

“…As a well-known traditional Chinese folk medicine, Scutellaria barbata D. Don (SB) has long been used as an important component in many Chinese medicine formulas to treat various types of cancer (32)(33)(34)(35). Previous studies proposed that extracts of SB (ESB) possess antitumor activity to suppress the growth of many types of cancer including CRC both in vitro and in vivo (36)(37)(38)(39)(40)(41)(42). In addition, we recently reported that ESB is able to induce cancer cell apoptosis via activation of the mitochondrion-dependent pathway and inhibit tumor angiogenesis through suppression of Hedgehog signaling (43)(44)(45).…”

Section: Scutellaria Barbata D Don Induces G1/s Arrest Via Modulatiomentioning

confidence: 99%

Scutellaria barbata D. Don induces G1/S arrest via modulation of p53 and Akt pathways in human colon carcinoma cells

Wei

Lin

et al. 2013

Oncology Reports

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Cancer cells are characterized by an uncontrolled increase in cell proliferation. G1 to S transition is one of the two main checkpoints used by cells to control the cell cycle progress and cell proliferation. G1/S progression is highly regulated by multiple intracellular signaling transduction cascades including Akt and p53 pathways, which therefore becomes a promising target for the development of novel anticancer therapy. Scutellaria barbata D. Don (SB) is a major component in many Chinese medicine formulas that have long been used in China to clinically treat various cancers including colorectal cancer (CRC). Recently, we reported that the ethanol extract of SB (EESB) is able to induce cancer cell apoptosis via activation of the mitochondrion-dependent pathway and inhibit tumor angiogenesis through suppression of Hedgehog signaling. To further elucidate the precise mechanisms of its antitumor activity, in the present study we evaluated the effect of EESB on the proliferation of human colon carcinoma HT-29 cells and investigated the underlying molecular mechanism. We found that EESB could inhibit the proliferation of HT-29 cells through blocking the G1/S cell cycle progression. In addition, EESB treatment profoundly promoted antiproliferative p21 expression, but inhibited the expression of pro-proliferative PCNA, cyclin D1 and CDK4 in HT-29 cells. Moreover, the phosphorylation/activation of Akt was significantly suppressed by EESB treatment, whereas that of p53 was enhanced. These results suggest that EESB could effectively induce G1/S arrest in human colon carcinoma cells via modulation of multiple cell cycle-related signaling pathways.

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BZL101, a phytochemical extract from theScutellaria barbataplant, disrupts proliferation of human breast and prostate cancer cells through distinct mechanisms dependent on the cancer cell phenotype

Cited by 54 publications

References 29 publications

AIF‐mediated caspase‐independent necroptosis: A new chance for targeted therapeutics

AIF‐mediated caspase‐independent necroptosis: A new chance for targeted therapeutics

Scutellaria?barbata D. Don inhibits migration and invasion of colorectal cancer cells via suppression of PI3K/AKT and TGF‑β/Smad signaling pathways

Scutellaria barbata D. Don induces G1/S arrest via modulation of p53 and Akt pathways in human colon carcinoma cells

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