Cytotoxicity of anthraquinones from the roots of Pentas schimperi towards multi-factorial drug-resistant cancer cells.

Abstract:

INTRODUCTION:Multidrug resistance in cancer represents a major problem in chemotherapy. The present study was designed to assess the cytotoxicity of anthraquinones from Pentas schimperi, namely damnacanthal (1), damnacanthol (2), 3-hydroxy-2-hydroxymethyl anthraquinone (3) and schimperiquinone B (4) against nine drug-sensitive and multidrug resistant (MDR) cancer cell lines. METHODS:The resazurin reduction assay was used to evaluate the cytotoxicity of the above compounds, whilst caspase-Glo assay was used to detect the activation of caspases enzymes by compounds 1 and 2. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species were all analyzed via flow cytometry. RESULTS:Anthraquinones 1 and 2 displayed cytotoxic effects with IC50 values below 81 μM on all the nine tested cancer cell lines whilst 3 and 4 displayed selective activities. The recorded IC50 values for compounds 1 and 2 ranged from 3.12 μM and 12.18 μM (towards leukemia CCRF-CEM cells) and from 30.32 μM and 80.11 μM (towards gliobastoma U87MG.ΔEGFR cells) respectively, and from 0.20 μM (against CCRF-CEM cells) to 195.12 μM (against CEM/ADR5000 cells) for doxorubicin. Compounds 1 and 2 induced apoptosis in CCRF-CEM leukemia cells, mediated by the disruption of the MMP and increase in ROS production. CONCLUSIONS:Anthraquinones from Pentas schimperi and mostly 1 and 2 are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug resistant cancers.

journal_name

Invest New Drugs

authors

Kuete V,Donfack AR,Mbaveng AT,Zeino M,Tane P,Efferth T

doi

10.1007/s10637-015-0268-9

subject

Has Abstract

pub_date

2015-08-01 00:00:00

pages

861-9

issue

4

eissn

0167-6997

issn

1573-0646

journal_volume

33

pub_type

杂志文章
  • Phase II study of iproplatin (CHIP) in patients with cisplatin-refractory germ cell tumors; the need for alternative strategies in the investigation of new agents in GCT.

    abstract::Fifteen patients with advanced, cisplatin-refractory germ cell tumors (GCT) were treated with iproplatin (CHIP). No objective responses were noted in any of the patients treated. By restricting the entry criteria to heavily pre-treated patients, the identification of new active agents in phase II trials may be hindere...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00944190

    authors: Murphy BA,Motzer RJ,Bosl GJ

    更新日期:1992-11-01 00:00:00

  • T cell cytotoxicity toward hematologic malignancy via B7-H3 targeting.

    abstract::T cells are important effectors in anti-tumor immunity, and aberrant expression of B7 family members may contribute to tumor evasion. In this study, we analyzed expression of costimulatory molecules on human hematologic tumor cells and explored whether B7-H3, a member of the B7 superfamily, is an effective target for ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-019-00819-y

    authors: Sun X,Yu Y,Ma L,Xue X,Gao Z,Ma J,Zhang M

    更新日期:2020-06-01 00:00:00

  • Prolonged infusion of gemcitabine in advanced solid tumors: a phase-I-study.

    abstract:BACKGROUND:Gemcitabine is a pro-drug that has to be phosphorylated to gemcitabine-triphosphate in order to exhibit its antineoplastic activity. This reaction involves the enzyme deoxycytidine kinase which is saturated at plasma concentrations following standard 30-min infusions. Pharmacological studies indicate that pr...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1007/s10637-005-5859-4

    authors: Schmid P,Schweigert M,Beinert T,Flath B,Sezer O,Possinger K

    更新日期:2005-03-01 00:00:00

  • The new isothiocyanate 4-(methylthio)butylisothiocyanate selectively affects cell-cycle progression and apoptosis induction of human leukemia cells.

    abstract::We investigated proliferation and apoptosis induction in Jurkat T-leukemia cells by the new isothiocyanate 4-(methylthio)butylisothiocyanate (MTBITC). To help elucidate whether the effects of MTBITC are specific for cancer cells, we tested MTBITC on freshly isolated, non-transformed human peripheral T lymphocytes. The...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1023/B:DRUG.0000011788.19754.54

    authors: Fimognari C,Nüsse M,Iori R,Cantelli-Forti G,Hrelia P

    更新日期:2004-04-01 00:00:00

  • Phase II study of flutamide as second line chemotherapy in patients with advanced pancreatic cancer.

    abstract::Androgen receptors are present in both pancreatic cancer tissue and cell lines. Flutamide is a potent antiandrogen widely used in clinical practice for patients with metastatic prostate cancer. This Phase II trial was undertaken to evaluate the impact of flutamide in patients with advanced pancreatic adenocarcinoma wh...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1023/a:1005989519350

    authors: Sharma JJ,Razvillas B,Stephens CD,Hilsenbeck SG,Sharma A,Rothenberg ML

    更新日期:1997-01-01 00:00:00

  • The PG500 series: novel heparan sulfate mimetics as potent angiogenesis and heparanase inhibitors for cancer therapy.

    abstract::Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellula...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-009-9245-5

    authors: Dredge K,Hammond E,Davis K,Li CP,Liu L,Johnstone K,Handley P,Wimmer N,Gonda TJ,Gautam A,Ferro V,Bytheway I

    更新日期:2010-06-01 00:00:00

  • Phase II trial of low-dose N-(phosphonacetyl)-disodium L-aspartic acid and high-dose 24-hour infusional 5-fluorouracil in advanced gastric adenocarcinoma. A Southwest Oncology Group study.

    abstract::N-(phosphonacetyl)-disodium L-aspartic acid (PALA) demonstrates a synergistic antitumor effect when combined with 5-Fluorouracil (5-FU) in in vitro studies. In a Phase II trial, 23 eligible patients with unresectable or metastatic adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250 mg/M2) follo...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00180821

    authors: Martino RL,Fleming TR,Morrell LM,Ardalan B,Richman SP,Macdonald JS

    更新日期:1996-01-01 00:00:00

  • Multifunctional 5-aminolevulinic acid prodrugs activating diverse cell-death pathways.

    abstract::Herein we describe a series of multifunctional 5-aminolevulinic-acid (ALA) prodrugs for photodynamic dependent and independent cancer therapy (PDT). We studied the cell-death mechanisms in glioblastoma U251 cells treated with four ALA-prodrugs: (1) AlaAcBu, that releases ALA, acetaldehyde, and butyric acid; (2) AlaFaB...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-011-9669-6

    authors: Berkovitch-Luria G,Weitman M,Nudelman A,Rephaeli A,Malik Z

    更新日期:2012-06-01 00:00:00

  • Phase II trial of topotecan in advanced gastric cancer: a Southwest Oncology Group study.

    abstract::Topotecan (NSC 609099) is a camptothecin analogue that demonstrated activity against a variety of human tumors in preclinical studies. A phase II trial was performed with topotecan given to patients with locally advanced or metastatic adenocarcinoma of the stomach. Topotecan was administered IV Bolus over 30 minutes o...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1023/a:1005899720463

    authors: Benedetti JK,Burris HA 3rd,Balcerzak SP,Macdonald JS

    更新日期:1997-01-01 00:00:00

  • Oral idarubicin in non-Hodgkin's lymphomas.

    abstract::Idarubicin (DMDR), a new analogue of daunorubicin, was administered orally once every 3 weeks at the dose of 40 to 45 mg/m2 to 20 evaluable patients with non-Hodgkin's lymphomas (NHL). Eighty-six percent of patients with favorable histology and 54% with unfavorable histology (intermediate and high grade as IWF) achiev...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00179594

    authors: Lopez M,Di Lauro L,Papaldo P

    更新日期:1986-01-01 00:00:00

  • Distribution, elimination, metabolism and bioavailability of hexamethylenebisacetamide in rats.

    abstract::Hexamethylenebisacetamide (HMBA), an in vitro differentiating agent, was studied for its pharmacodynamic actions in animals. Plasma stability, organ distribution, excretion, oral bioavailability, and estimates of pharmacokinetic parameters and acute lethality were determined in rats. The single dose intraperitoneal LD...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00179430

    authors: Litterst CL,Roth JS,Kelley JA

    更新日期:1985-01-01 00:00:00

  • A phase I study of sulofenur in refractory pediatric malignant solid tumors.

    abstract::The diarylsulfonylureas have shown promise in xenograft models of childhood cancer. Sulofenur has been evaluated in phase I and II trials in adults with a variety of solid tumors, but the toxicity and maximum tolerated dose of sulofenur in children and adolescents have not been determined. In a phase I study, sulofenu...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF02614222

    authors: Pratt CB,Bowman LC,Marina N,Pappo A,Avery L,Luo X,Meyer WH

    更新日期:1995-01-01 00:00:00

  • Flutamide in unresectable pancreatic adenocarcinoma: a randomized, double-blind, placebo-controlled trial.

    abstract:PURPOSE:To evaluate the impact of flutamide on survival of patients with unresectable pancreatic cancer. METHODS:This single institution, randomized, double-blind, placebo controlled study compared flutamide in the dose of 250 mg three times daily (n = 23) versus placebo (n = 23) in patients with histologically proven...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s10637-005-3536-2

    authors: Negi SS,Agarwal A,Chaudhary A

    更新日期:2006-05-01 00:00:00

  • A phase II trial of oral etoposide with mitoxantrone and ifosfamide/mesna consolidated with intravenous etoposide, methylprednisolone, high-dose arabinoside, and cisplatin as salvage therapy for relapsing and/or refractory lymphomas.

    abstract:PURPOSE:To evaluate the response to oral Etoposide when combined with mesna, ifosfamide, and mitoxantrone in patients with relapsed and/or refractory lymphoma. To evaluate response and its duration after administration of intravenous Etoposide, methylprednisolone, high-dose cytosine arabinoside, and cisplatin (ESHAP) a...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00873962

    authors: Romaguera JE,Rodriguez MA,Hagemeister FB,McLaughlin P,Swan F,Moore DF Jr,Sarris AH,Younes A,Hill D,Cabanillas F

    更新日期:1994-01-01 00:00:00

  • Targeting specificity protein 1 transcription factor and survivin using tolfenamic acid for inhibiting Ewing sarcoma cell growth.

    abstract::Transcription factor Specificity protein 1 (Sp1) and its downstream target survivin (inhibitor of apoptosis protein), play major roles in the pathogenesis of various cancers. Ewing Sarcoma (ES) is a common soft tissue/bone tumor in adolescent and young adults. Overexpression of survivin is also linked to the aggressiv...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-016-0417-9

    authors: Shelake S,Sankpal UT,Paul Bowman W,Wise M,Ray A,Basha R

    更新日期:2017-04-01 00:00:00

  • Eugenol inhibits cell proliferation via NF-κB suppression in a rat model of gastric carcinogenesis induced by MNNG.

    abstract::The modulation of intracellular nuclear factor-kappaB (NF-κB) signaling pathway involved in the deregulated expression of cell proliferation and cell cycle regulatory molecules is a pragmatic approach for chemoprevention. Eugenol (4-allyl-1-hydroxy-2-methoxybenzene), a natural phenolic constituent of oils of cloves is...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-009-9345-2

    authors: Manikandan P,Vinothini G,Vidya Priyadarsini R,Prathiba D,Nagini S

    更新日期:2011-02-01 00:00:00

  • Results of a Phase II trial of gemcitabine, mitoxantrone, and rituximab in relapsed or refractory mantle cell lymphoma.

    abstract:BACKGROUND:Gemcitabine (G) has shown activity in mantle cell lymphoma (MCL) as a single agent. The combination of mitoxantrone (M) and rituximab (R) is also active in MCL. The primary objective of this study was to determine the efficacy of G+M+R in relapsed or refractory MCL. PATIENTS AND METHODS:Sixteen patients wer...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s10637-008-9191-7

    authors: Garbo LE,Flynn PJ,MacRae MA,Rauch MA,Wang Y,Kolibaba KS

    更新日期:2009-10-01 00:00:00

  • Evaluation of pyrazoloacridine in patients with advanced pancreatic carcinoma.

    abstract:PURPOSE:Pyrazoloacridine (PZA) is an acridine derivative selected for clinical development because of broad pre-clinical antitumor activity and solid tumor selectivity. Phase I evaluations with PZA have demonstrated predictable toxicity and suggested clinical efficacy. A phase II trial in patients with previously untre...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1023/a:1006087114621

    authors: Zalupski MM,Shields AF,Philip PA,Kraut M,LoRusso P,Heilbrun LK,Vaitkevicius V

    更新日期:1998-01-01 00:00:00

  • Cellular pharmacology of fluorinated pyrimidines in vivo in man.

    abstract::Fluorinated pyrimidines, particularly 5-fluorouracil (FUra), have been the subject of intense and almost continuous basic and clinical study since development in the late 1950's by Dr. Charles Heidelberger. Despite this intensive effort, the most important mechanisms by which FUra influences tumor growth in individual...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,评审

    doi:10.1007/BF00178188

    authors: Kovach JS,Beart RW Jr

    更新日期:1989-04-01 00:00:00

  • A phase I and pharmacokinetic study of trimetrexate using a 24-hour continuous-injection schedule.

    abstract::Trimetrexate (TMTX) is an analog of methotrexate and a potent inhibitor of the enzyme dihydrofolate reductase. In this phase I study, TMTX was given intravenously to 32 patients as a constant infusion over 24 hours every 28 days. The maximum-tolerated dose of TMTX was 200 mg/m2, with myelosuppression as the dose-limit...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00177251

    authors: Allegra CJ,Jenkins J,Weiss RB,Balis F,Drake JC,Brooks J,Thomas R,Curt GA

    更新日期:1990-05-01 00:00:00

  • The flavonoid luteolin suppresses infantile hemangioma by targeting FZD6 in the Wnt pathway.

    abstract::Infantile hemangioma is the most common vascular tumor of childhood. It is characterized by clinical expansion of endothelial cells and promoted by angiogenic factors. Luteolin is a flavonoid compound that carries anti-cancer and anti-angiogenesis properties. The study aimed to investigate the effect of luteolin in tr...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-020-01052-8

    authors: Dai Y,Zheng H,Liu Z,Wang Y,Hu W

    更新日期:2021-01-07 00:00:00

  • Severe acute interstitial lung disease in a patient with anaplastic lymphoma kinase rearrangement-positive non-small cell lung cancer treated with alectinib.

    abstract::Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib tre...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-015-0284-9

    authors: Yamamoto Y,Okamoto I,Otsubo K,Iwama E,Hamada N,Harada T,Takayama K,Nakanishi Y

    更新日期:2015-10-01 00:00:00

  • A phase II trial of diaziquone (AZQ) in mixed mesodermal sarcomas of the uterus. A Gynecologic Oncology Group study.

    abstract::AZQ was given intravenously to 23 patients with mixed mesodermal sarcoma of the uterus refractory to conventional treatment at a dose of 22.5-30 mg/m2 q three weeks. There was one partial response lasting seven weeks and one drug-related death. Based upon the activity observed in this trial, there does not appear to b...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1007/BF00194555

    authors: Slayton RE,Blessing JA,Clarke-Pearson D

    更新日期:1991-02-01 00:00:00

  • Phase I trial of docetaxel given every 3 weeks and daily lenalidomide in patients with advanced solid tumors.

    abstract:PURPOSE:Cytotoxic and anti-angiogenic drugs are efficacious in malignancies. This trial was undertaken to evaluate the toxicity of a novel regimen combining docetaxel and lenalidomide. PATIENTS AND METHODS:Patients with advanced solid tumors were eligible. Docetaxel was administered on day 1, and lenalidomide was give...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-008-9200-x

    authors: Sanborn SL,Gibbons J,Krishnamurthi S,Brell JM,Dowlati A,Bokar JA,Nock C,Horvath N,Bako J,Remick SC,Cooney MM

    更新日期:2009-10-01 00:00:00

  • A phase I trial of combination trastuzumab, lapatinib, and bevacizumab in patients with advanced cancer.

    abstract:PURPOSE:Preclinical data indicate that combination HER2-directed and anti-VEGF therapy may bypass resistance to trastuzumab. A phase I trial was performed to assess safety, activity, and correlates. EXPERIMENTAL DESIGN:Patients with advanced, refractory malignancy were enrolled (modified 3 + 3 design with expansions f...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-014-0173-7

    authors: Falchook GS,Moulder S,Naing A,Wheler JJ,Hong DS,Piha-Paul SA,Tsimberidou AM,Fu S,Zinner R,Janku F,Jiang Y,Huang M,Parkhurst KL,Kurzrock R

    更新日期:2015-02-01 00:00:00

  • A phase 1 dose-escalating study of pegylated recombinant human arginase 1 (Peg-rhArg1) in patients with advanced hepatocellular carcinoma.

    abstract:BACKGROUND:Hepatocellular carcinoma (HCC) cells are auxotrophic for arginine, depletion of which leads to tumour regression. The current study evaluated safety, pharmacokinetics (PK)/ pharmacodynamics (PD) parameters, and potential anti-tumor activity of pegylated recombinant human arginase 1 (peg-rhArg1) in advanced H...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-012-9807-9

    authors: Yau T,Cheng PN,Chan P,Chan W,Chen L,Yuen J,Pang R,Fan ST,Poon RT

    更新日期:2013-02-01 00:00:00

  • SHetA2 interference with mortalin binding to p66shc and p53 identified using drug-conjugated magnetic microspheres.

    abstract::SHetA2 is a small molecule flexible heteroarotinoid (Flex-Het) with promising cancer prevention and therapeutic activity. Extensive preclinical testing documented lack of SHetA2 toxicity at doses 25 to 150 fold above effective doses. Knowledge of the SHetA2 molecular target(s) that mediate(s) the mechanism of SHetA2 a...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-013-0041-x

    authors: Benbrook DM,Nammalwar B,Long A,Matsumoto H,Singh A,Bunce RA,Berlin KD

    更新日期:2014-06-01 00:00:00

  • Evaluation of gemcitabine in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Southwest Oncology Group phase II study.

    abstract::A phase II trial of gemcitabine (Gemzar), a nucleoside analogue with broad activity in solid tumors, was performed in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. A total of 26 eligible patients were registered to receive a dose of 1250 mg/m2 weekly for 3 weeks, followed by a 1 w...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1023/a:1010657609609

    authors: Samlowski WE,Gundacker H,Kuebler JP,Giguere JK,Mills GM,Schuller DE,Ensley JF

    更新日期:2001-01-01 00:00:00

  • Cytotoxicity of withaferin A in glioblastomas involves induction of an oxidative stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling pathways.

    abstract::Withaferin A (WA), a steroidal lactone derived from the plant Vassobia breviflora, has been reported to have anti-proliferative, pro-apoptotic, and anti-angiogenic properties against cancer growth. In this study, we identified several key underlying mechanisms of anticancer action of WA in glioblastoma cells. WA was f...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-012-9888-5

    authors: Grogan PT,Sleder KD,Samadi AK,Zhang H,Timmermann BN,Cohen MS

    更新日期:2013-06-01 00:00:00

  • Phase I dose escalation and pharmacokinetic evaluation of two different schedules of LY2334737, an oral gemcitabine prodrug, in patients with advanced solid tumors.

    abstract:BACKGROUND:This Phase-I-study aimed to determine the recommended Phase-II-dosing-schedule of LY2334737, an oral gemcitabine prodrug, in patients with advanced/metastatic solid tumors. Pharmacokinetics, cytokeratin-18 (CK18) levels, genetic polymorphisms, and antitumor activity were additionally evaluated. METHODS:Pati...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-015-0286-7

    authors: Faivre SJ,Olszanski AJ,Weigang-Köhler K,Riess H,Cohen RB,Wang X,Myrand SP,Wickremsinhe ER,Horn CL,Ouyang H,Callies S,Benhadji KA,Raymond E

    更新日期:2015-12-01 00:00:00