Ham-Wasserman Lecture

Wang, Zhenyi

doi:10.1182/asheducation-2003.1.1

Cited by 44 publications

(26 citation statements)

References 93 publications

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“…32 Previous investigations showed that tanshinone IIA has antioxidant properties 6 and cytotoxic activity against multiple human cancer cell lines; 7 inhibited the proliferation of mouse P388 lymphocytic leukemia cells 8 and human hepatoma cells; [9][10][11][12] induced apoptosis of human hepatocellular carcinoma cells, [10][11][12] human promyelocytic leukemia cells (HL60) and human erythroleukemia cells (K562); 13,14 and induced differentiation of human leukemia cells. [15][16][17] However, to our knowledge, there have been no studies on the anticancer activity of tanshinone IIA in human breast cancer cells in vitro and in vivo except for one report of an anticancer effect on mouse hepatic carcinoma. 18 Our study confirms that tanshinone IIA has strong dosedependent and time-dependent anticancer activity in human breast cancer cells (IC 50 ¼ 0.25 mg/ml) and inhibited the colony growth potential of cancer cells in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…7 Studies in vitro have shown that tanshinone IIA inhibited the proliferation of mouse P388 lymphocytic leukemia cells 8 and human hepatoma cells; [9][10][11][12] induced apoptosis of human hepatocellular carcinoma cells, [10][11][12] human promyelocytic leukemic cells (HL60) and human erythroleukemic cells (K562); 13,14 and induced differentiation of human leukemia cells. [15][16][17] However, few studies have reported anticancer activity of tanshinone IIA in vivo except for one on mouse hepatic carcinoma. 18 Epidemiologic studies have suggested that antioxidant supplements might reduce the risk of breast cancer recurrence or breast cancer-related mortality.…”

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confidence: 99%

“…19 Many naturally occurring agents have shown cancer chemopreventive potential in a variety of bioassay systems and animal models with relevance to human disease; 20 e.g., genistein, one of the major soy isoflavones, has antioxidant properties, is a potent inhibitor of angiogenesis and metastasis and is a promising reagent for cancer chemoprevention and/or treatment. 21 Based on its antioxidant properties, cytotoxic activity against multiple human cancer cells, induction of apoptosis and differentiation of human hepatocellular carcinoma cells and leukemia cells, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] we hypothesized that tanshinone IIA might be a candidate agent for human breast cancer treatment and/or chemoprevention. However there are no such reports.…”

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Potential anticancer activity of tanshinone IIA against human breast cancer

et al. 2005

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Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen, a widely used Chinese herbal medicine. It has antioxidant properties and cytotoxic activity against multiple human cancer cell lines, inducing apoptosis and differentiation of some human cancer cell lines. Our purpose was to confirm its anticancer activity on human breast cancer in vitro and in vivo and to elucidate the mechanism of its activity. Human breast cancer cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation and gene expression profiling after treatment with tanshinone IIA. Seven nude mice bearing human breast infiltrating duct carcinoma orthotopically were tested for anticancer activity and expression of caspase-3 in vivo by s.c. injection of tanshinone IIA at a dose of 30 mg/kg 3 times/week for 10 weeks. Tanshinone IIA demonstrated a dose-and time-dependent inhibitory effect on cell growth (IC 50 = 0.25 mg/ml), and it significantly inhibited colony formation and BrdU incorporation of human breast cancer cells. Oligonucleotide microarray analysis identified 41 upregulated (1.22%) and 24 downregulated (0.71%) genes after tanshinone IIA treatment. Upregulated genes were involved predominantly in cycle regulation, cell proliferation, apoptosis, signal transduction and transcriptional regulation; and downregulated genes were associated mainly with apoptosis and extracellular matrix/adhesion molecules. A 44.91% tumor mass volume reduction and significant increase of casepase-3 protein expression were observed in vivo. Our findings suggest that tanshinone IIA might have potential anticancer activity on both ER-positive and -negative breast cancers, which could be attributed in part to its inhibition of proliferation and apoptosis induction of cancer cells through upregulation and downregulation of multiple genes involved in cell cycle regulation, cell proliferation, apoptosis, signal transduction, transcriptional regulation, angiogenesis, invasive potential and metastatic potential of cancer cells. ADPRTL1 might be the main target at which tanshinone IIA acted. ' 2005 Wiley-Liss, Inc.Key words: tanshinone IIA; anticancer activity; breast cancer; growth inhibition; apoptosis Breast cancer is a major public health problem in the United States and in most industrialized countries.1 It is the most common cancer in women and the leading cause of cancer death among women 35-54 years of age.2 The rising incidence and poor prognosis of breast cancer cases have prompted a search for additional preventive and therapeutic modalities.Danshen (Salvia miltiorrhiza Bunge) is a widely used Chinese herbal medicine; its extracts contain diterpene quinone and phenolic acid derivatives, including tanshinone (I, IIA and IIB), cryptotanshinone, isocryptotanshinone, miltirone, tanshinol (I and II) and salviol. These compounds have antioxidant properties and protect against lipid peroxidation in vitro and in vivo, making them potential antidotes for free radical-based disorders.3-5 Tanshinone IIA is a derivative of...

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Section: Discussionmentioning

confidence: 99%

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Potential anticancer activity of tanshinone IIA against human breast cancer

et al. 2005

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“…The planar phenanthrene ring of the tanshinones may be essential for their interaction with DNA molecules, whereas the furano-oquinone moiety could be responsible for the production of reactive-free radicals in close vicinity to bases, causing DNA damage and inducing cytotoxicity in different human cancer cell lines (8). Several studies have shown that tanshinone IIA inhibits the proliferation of mouse P388 lymphocytic leukemia cells (9) and human hepatoma cells in vitro (10)(11)(12)(13); tanshinone IIA can also induce apoptosis in human hepatocellular carcinoma cells (11)(12)(13), human promyelocytic leukemia cells (HL60), and human erythroleukemic cells (K562) (14,15); Finally, tanshinone IIA has been shown to induce differentiation of human leukemia cells (16)(17)(18). Recently, tanshinone IIA has been reported to inhibit the proliferation of the ER-positive human breast cancer cells and the ER-negative cells MDA-MB-231 in vitro (20); the associated mechanism, however, is not clearly understood.…”

Section: Introductionmentioning

confidence: 99%

Experimental study of the anti-cancer mechanism of tanshinone IIA against human breast cancer

Lü

Zhang²,

Zhang³

et al. 2009

Int J Mol Med

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Abstract. Tanshinone IIA is a widely used Chinese herbal medicine isolated from Danshen (Salvia miltiorrhiza). Recent studies indicate that tanshinone IIA may have antiinflammatory and anti-oxidant properties, as well as cytotoxic activities against multiple human cancer cell lines. This study was performed to determine the anticancer activity of tanshinone IIA on human breast cancer cells in vitro and in vivo and to elucidate the underlying mechanism of this activity. Human breast cancer cell lines (estrogen receptor-positive and -negative) were treated with tanshinone IIA and tamoxifen. The inhibitory effects of tanshinone IIA and tamoxifen on breast cancer cell proliferation were examined using MTT assays, BrdU incorporation, immunohistochemistry and flow cytometry. Upon treatment with tanshinone IIA, breast cancer cell proliferation was significantly inhibited in a dose-and time-dependent manner (IC 50 = 0.25 μg/ml) and apoptotic cell populations increased, while tamoxifen inhibited only ER-positive breast cancer cells prominently and had no effect on ER-negative cells. In addition, tamoxifen had significantly weaker inhibitory effect than tanshinone IIA on ER-positive breast cancer cells in vitro and in vivo. Furthermore, tanshinone IIA decreased the expression of P53 and bcl-2, but not of cerbB-2, in estrogen receptorpositive and negative xenografted nude mice. Our findings suggest that tanshinone IIA might have potential anti-cancer activity that is stronger than tamoxifen in both ER-positive and ER-negative breast cancers. This function could be attributed in part to its inhibition of proliferation and apoptosis induction in cancer cells via the downregulation of multiple genes involved in cell cycle regulation, cell proliferation, apoptosis and DNA synthesis.

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“…APML is traditionally being treated with combination ATRA (differentiating agent) and chemotherapy [3]. The morbidity and mortality due to chemotherapy and cost involved in treatment is a matter of great concern in resource limited setting [4].…”

Section: Introductionmentioning

confidence: 99%

Treatment of Acute Promyelocytic Leukemia with Single Agent Arsenic Trioxide: Experience from a Tertiary Care Center in India

Udupa

Thomas

Udupa

et al. 2016

Indian J Hematol Blood Transfus

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APML is a highly curable hematological malignancy which is treated with differentiation agents and chemotherapy. The morbidity caused by chemotherapy in the treatment of APML is a great cause of concern. We treated 12 patients with newly diagnosed APML with single agent arsenic trioxide between 2010 and 2014 irrespective of risk stratification. Out of 12 patient 2 patients died during induction. All the ten patients who completed induction, completed their consolidation and maintenance without any delays. One out of these ten patients relapsed 10 months after treatment. The remaining nine patients (80 %) are in molecular remission and are under regular follow up. The toxicity with arsenic was negligible and was very well tolerated. Hence arsenic trioxide as single agent can be offered as a standard alternative regimen to ATRA based chemotherapy in patients with economic constraints.

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Ham-Wasserman Lecture

Cited by 44 publications

References 93 publications

Potential anticancer activity of tanshinone IIA against human breast cancer

Potential anticancer activity of tanshinone IIA against human breast cancer

Experimental study of the anti-cancer mechanism of tanshinone IIA against human breast cancer

Treatment of Acute Promyelocytic Leukemia with Single Agent Arsenic Trioxide: Experience from a Tertiary Care Center in India

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