Tumor-selective cytotoxicity of benzo[c]phenanthridine derivatives from Toddalia asiatica Lam.

Iwasaki, Hiromichi; Okabe, Takafumi; Takara, Kensaku; Toda, Takayoshi; Shimatani, Masayuki; Oku, Hirosuke

doi:10.1007/s00280-009-1077-7

Cited by 39 publications

(45 citation statements)

References 11 publications

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“…Therefore, new drugs without significant side effects are absolutely required. For this aim, using medicinal plants with good efficacy and few side effects is a good strategy in comparison with allopathic medicine [6].…”

Section: Introductionmentioning

confidence: 99%

Suppression of Pulmonary Tumor Promotion and Induction of Apoptosis by Crocus sativus L. Extraction

Samarghandian

Afshari

Davoodi

2010

Appl Biochem Biotechnol

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Crocus sativus L., commonly known as saffron, is the raw material for one of the most expensive spice in the world, and it has been used in folk medicine for centuries. We investigated the potential of the ethanolic extract of saffron to induce cytotoxic and apoptosis effects in carcinomic human alveolar basal epithelial cells (A549), a commonly used cell culture system for in vitro studies on lung cancer. The cells were cultured in Dulbecco's modified Eagle's medium with 10% fetal bovine serum treated with different concentrations of the ethanolic extract of saffron for two consecutive days. Cell viability was quantitated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Apoptotic cells were determined using annexin V-fluorescein isothiocyanate by flow cytometry. Saffron could decrease the cell viability in the malignant cells as a concentration- and time-dependent manner. The IC₅₀ values against the A549 cell lines were determined as 1,200 and 650 μg/ml after 24 and 48 h, respectively. Saffron-induced apoptosis of the A549 cells in a concentration-dependent manner, as determined by flow cytometry histogram of treated cells that induced apoptotic cell death, is involved in the toxicity of saffron. It might be concluded that saffron could cause cell death in the A549 cells, in which apoptosis plays an important role. Saffron could also be considered as a promising chemotherapeutic agent in lung cancer treatment in future.

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Section: Introductionmentioning

confidence: 99%

Suppression of Pulmonary Tumor Promotion and Induction of Apoptosis by Crocus sativus L. Extraction

Samarghandian

Afshari

Davoodi

2010

Appl Biochem Biotechnol

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“…1A), a natural bioactive phytochemical alkaloid derived from Zanthoxylum nitidum (Roxb) DC, was initially reported to have significant antioxidant, antifungal, anti-inflammatory, and analgesic bioactivities (15). Subsequent studies proved that nitidine chloride exhibited anticancer potential through the induction of apoptosis in a wide variety of human tumor cell lines, such as lung, breast, liver, oral, and osteosarcoma in vitro (16). Activation of caspase-3 (17), inhibition of topoisomerase y (18), and suppression of human immunodeficiency virus reverse transcriptase (19) have been implicated in niditine-mediated anticancer and immunomodulatory function.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of STAT3 Signaling Pathway by Nitidine Chloride Suppressed the Angiogenesis and Growth of Human Gastric Cancer

Chen

Wang

Lin

et al. 2012

Molecular Cancer Therapeutics

139

122

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STAT3 has been strongly implicated in human malignancies, and constitutive activation of STAT3 serves a crucial role in cell survival, angiogenesis, immune evasion, and inflammation. In this study, we showed that nitidine chloride, a natural phytochemical alkaloid derived from Zanthoxylum nitidum (Roxb) DC, exerts potent anticancer activity through STAT3 signaling cascade. Nitidine chloride dose dependently suppressed VEGFinduced endothelial cell proliferation, migration, and tubular structure formation in vitro and dramatically reduced VEGF-triggered neovascularization in mouse cornea and Matrigel plugs in vivo. This angiogenesis inhibition mediated by nitidine chloride was well interpreted by the suppression of Janus kinase 2/STAT3 signaling and STAT3 DNA-binding activity in endothelial cells. Furthermore, nitidine chloride suppressed the constitutively activated STAT3 protein, its DNA-binding activity, and the expression of STAT3-dependent target genes, including cyclin D1, Bcl-xL, and VEGF in human gastric cancer cells. Consistent with the earlier findings, nitidine chloride inhibited gastric tumor cell growth and induced tumor cell apoptosis in vitro and effectively suppressed the volume, weight, and microvessel density of human SGC-7901 gastric solid tumors (n ¼ 8) at a dosage of 7 mg/kg/d (intraperitoneal injection). Immunohistochemistry and Western blot analysis further revealed that the expression of STAT3, CD31, and VEGF protein in xenografts was remarkably decreased by the alkaloid. Taken together, we propose that nitidine chloride is a promising anticancer drug candidate as a potent STAT3 signaling inhibitor. Mol Cancer Ther; 11(2); 277-87. Ó2011 AACR.

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“…T. asiatica is commonly referred to as ''wild orange tree'' and is widely recognized as a medicinal plant in Africa, India, China and Japan. All parts of the plant are believed to have medicinal properties, and its root, bark, and leaves have been used for the treatment of many diseases including diabetes [1][2][3]. Recent studies have supported the beneficial effects of T. asiatica [4], and Stephen et al clearly showed antidiabetic properties of T. asiatica (ethyl acetate extract from leaves) in streptozotocin-induced diabetic rats [3].…”

Section: Introductionmentioning

confidence: 94%

Aculeatin, a coumarin derived from Toddalia asiatica (L.) Lam., enhances differentiation and lipolysis of 3T3-L1 adipocytes

Watanabe

Kato

Ito

et al. 2014

Biochemical and Biophysical Research Communications

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Tumor-selective cytotoxicity of benzo[c]phenanthridine derivatives from Toddalia asiatica Lam.

Abstract: This study thus proves the effectiveness of benzo[c]phenanthridine derivatives as anti-cancer agent in vivo for the first time, and discusses the mechanisms responsible for the selective cytotoxicity.

Cited by 39 publications

References 11 publications

Suppression of Pulmonary Tumor Promotion and Induction of Apoptosis by Crocus sativus L. Extraction

Suppression of Pulmonary Tumor Promotion and Induction of Apoptosis by Crocus sativus L. Extraction

Inhibition of STAT3 Signaling Pathway by Nitidine Chloride Suppressed the Angiogenesis and Growth of Human Gastric Cancer

Aculeatin, a coumarin derived from Toddalia asiatica (L.) Lam., enhances differentiation and lipolysis of 3T3-L1 adipocytes

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