Effects of Pien Tze Huang (片仔癀) on angiogenesis in vivo and in vitro

Shen, Aling; Fu, Hong; Liu, Liya; Lin, Jiumao; Zhuang, Qunchuan; Zhang, Hong; Peng, Jun

doi:10.1007/s11655-012-1121-z

Cited by 35 publications

(29 citation statements)

References 23 publications

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“…Modern pharmacological studies have proposed that PZH not only exhibits therapeutic effects on hepatocellular carcinoma and CRC in clinical trials (13,14), but also inhibits the growth of human colon carcinoma cells by activating mitochondrion-dependent apoptosis (15). Moreover, PZH reportedly suppressed the cell proliferation and tumor angiogenesis of CRC carcinoma cells in vitro and in vivo (16,17). To elucidate further the antitumor mechanism of action of PZH, we evaluated its efficacy against tumor invasiveness in vivo and in vitro and investigated its underlying molecular mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Pien Tze Huang inhibits liver metastasis by targeting TGF-β signaling in an orthotopic model of colorectal cancer

et al. 2015

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Abstract.Metastasis is the leading cause of cancer-related mortality in almost all types of cancers, including colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT) is a critical process during the metastatic cascade. This process may be a potential target for the diagnosis and treatment of CRC. Pien Tze Huang (PZH), a well-known traditional Chinese formula, has been demonstrated to be clinically effective in treating various types of human malignancies, including CRC. Our published data suggest that PZH can induce apoptosis, as well as inhibit cell proliferation and tumor angiogenesis, thus suppressing CRC growth in vitro and in vivo. We evaluated the therapeutic efficacy of PZH against CRC metastasis using a CRC liver metastasis mouse model to further explore the mechanisms underlying the antitumor action of PZH. MTT, migration, and Matrigel invasion assays were used to assess the effect of PZH on cell viability, migration and invasion. We then established an orthotopic liver metastasis model of colon cancer using microsurgical techniques. Mice were intragastrically administered 234 mg/kg/day dose of either PZH or saline for 14 days. The body and tumor weights of the mice were measured after they were sacrificed. Moreover, we examined the effect of PZH inhibition on liver metastasis. Finally, EMT-related proteins and the TGF-β signaling pathway were assessed using immunohistochemical staining (IHS). The present data revealed that PZH significantly inhibited the migration and invasion of CT-26 cells in a dose-dependent manner, which affirmed the inhibitory effect of PZH on CRC cell metastasis. No significant change was observed between the in vivo primary tumor growth and body weight. However, the control group had five cases of liver metastasis (5/6), whereas one case was found in the PZH group (1/6). Thus, PZH exhibited therapeutic efficacy against CRC metastasis without apparent toxicity. The inhibitory effect of PZH on EMT resulted in an increase in E-cadherin expression, as well as a decrease in N-cadherin expression. In addition, PZH significantly inhibited TGF-β, as well as the phosphorylation of Smad2/3 and Smad4 in the tumor tissues, indicating its suppressive action on TGF-β signaling. These molecular effects ultimately resulted in the inhibition of cancer cell EMT and tumor metastasis.

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Section: Introductionmentioning

confidence: 99%

Pien Tze Huang inhibits liver metastasis by targeting TGF-β signaling in an orthotopic model of colorectal cancer

et al. 2015

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“…In the present study, Migration assays. Migration ability of the CRC cell lines was evaluated by wound-healing, as previously described (15). Briefly, CRC cells were seeded into 6-well plates (10 6 cells/well in 2 ml culture medium).…”

Section: Detection Of Apoptosismentioning

confidence: 99%

“…In fact, PZH has long been used as an alternative treatment strategy for cancers in China and Southeast Asia. Previously, we reported that PZH can inhibit CRC growth in vivo and in vitro via promotion of apoptosis and suppression of proliferation of cancer stem cells (CSCs) as well as inhibition of angiogenesis and reversal of multidrug resistance through multiple pathways while causing minimal side-effects (13)(14)(15)(16)(17). Recently, we found that PZH also prevents metastasis by inhibiting the progression of epithelial-mesenchymal transition (EMT) (18,19), but the underlying mechanism of the antimetastasis effects of PZH are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Pien Tze Huang suppresses VEGF-C-mediated lymphangiogenesis in colorectal cancer

et al. 2016

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Abstract. Colorectal cancer (CRC) is one of the most common malignancies worldwide. The majority of patients are not suitable for surgery due to the presence of metastatic disease at the time of diagnosis, which has led to a high mortality rate for patients with CRC. Lymphangiogenesis, formation of new lymphatic vessels, plays an critical role in cancer progression particularly in cancer metastasis. Vascular endothelial growth factor-C (VEGF-C) has been previously demonstrated to play a pivotal role in cancer metastasis and therefore has become an attractive target for anticancer treatments. Pien Tze Huang (PZH) is a well-known traditional Chinese formula, which has exhibited significant therapeutic effects against CRC. However, the molecular mechanisms underlying its anticancer effects, particularly in regards to antimetastasis activity, still require further elucidation. In the present study, we evaluated the effects of PZH on cell migration and VEGF-C expression using various human CRC cell lines. Moreover, using a VEGF-Cstimulated human lymphatic endothelial cell (HLEC) model, we demonstrated that PZH suppresses lymphangiogenesis by attenuating cell migration and tube formation. This indicates that PZH possesses significant antimetastatic activity. Moreover, suppression of lymphangiogenesis by PZH via the downregulation of VEGF-C may be a potential molecular mechanism by which PZH inhibits metastasis in CRC.

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“…PZH a well-known traditional Chinese formula, first prescribed 450 years ago in the Ming Dynasty, has long been used in China for cancer treatment (22)(23)(24). Although it has been shown that PZH inhibits colon cancer growth via the induction of apoptosis and inhibition of tumor angiogenesis (26)(27)(28), the precise mechanism of its anticancer effect remains largely unclear. Therefore, in order for PZH to be developed further as an anticancer agent, its underlying molecular mechanism of action should be elucidated.…”

Section: Pzh Regulates the Expression Of Cyclin D1 And Cdk4 Inmentioning

confidence: 99%

“…In addition, in experimental animals PZH inhibits the growth of Ehrlich-Ascites tumor, gastric carcinoma, and hepatoma (25). Moreover, we recently reported that PZH is able to inhibit colon cancer growth both in vivo and in vitro via the promotion of apoptosis and inhibition of tumor angiogenesis (26)(27)(28) we evaluated its effect on the proliferation of the human colon carcinoma cell line Caco-2 and investigated the underlying molecular mechanism. Cell culture.…”

Section: Introductionmentioning

confidence: 99%

Pien Tze Huang inhibits the proliferation of human colon carcinoma cells by arresting G1/S cell cycle progression

Shen

Fu²,

Liu

et al. 2012

Oncology Letters

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Abstract. Pien Tze Huang (PZH), a well-known traditional Chinese formula prescribed 450 years ago in the Ming Dynasty, has been used in China and Southeast Asia for centuries as a folk remedy for various types of cancer, including colorectal cancer (CRC). Recently, we reported that PZH is capable of inhibiting colon cancer growth both in vivo and in vitro via the promotion of apoptosis and inhibition of tumor angiogenesis. To elucidate the mechanism of the tumoricidal activity of PZH, its effect on the proliferation of human colon carcinoma Caco-2 cells was evaluated and the underlying molecular mechanism was investigated. Results showed that PZH inhibited Caco-2 cell viability and survival in a dose-and/or time-dependent manner. In addition, PZH treatment was found to block the G1/S cell cycle progression. Moreover, PZH suppressed the mRNA and protein expression of pro-proliferative Cyclin D1 and CDK4. Findings of the present study suggest that inhibition of cell proliferation via the G1/S cell cycle arrest is a potential mechanism by which PZH can be effective in the treatment of cancer.

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Effects of Pien Tze Huang (片仔癀) on angiogenesis in vivo and in vitro

Abstract: PZH could inhibit angiogenesis in vivo in CAM model and in vitro on HUVECs, suggesting that inhibiting tumor angiogenesis might be one of the mechanisms by which PZH treats cancer.

Cited by 35 publications

References 23 publications

Pien Tze Huang inhibits liver metastasis by targeting TGF-β signaling in an orthotopic model of colorectal cancer

Pien Tze Huang inhibits liver metastasis by targeting TGF-β signaling in an orthotopic model of colorectal cancer

Pien Tze Huang suppresses VEGF-C-mediated lymphangiogenesis in colorectal cancer

Pien Tze Huang inhibits the proliferation of human colon carcinoma cells by arresting G1/S cell cycle progression

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