Inhibitory growth evaluation and apoptosis induction in MCF-7 cancer cells by new 5-aryl-2-butylthio-1,3,4-oxadiazole derivatives.

Abstract:

BACKGROUND:Cancer has become one of the global health issues and it is the life-threatening disease characterized by unrestrained growth of cells. Despite various advances being adopted by chemotherapeutic management, the use of the current anticancer drugs such as Doxorubicin, Asparginase, Methotrexate, Vincristine remains limited due to high toxicity, side effects and developing drug resistance. Apoptosis is a crucial cellular process and improper regulation of apoptotic signaling pathways may lead to cancer formation. Subsequently, the synthesis of effective chemotherapeutic agents that can induce apoptosis in tumor cell has emerged as a significant approach in cancer drug discovery. METHODS:The goal of this work is to develop a potential antitumor agent exerting significant inhibitory effects on cancer cell and low cytotoxicity, for which we focused on the structural features of 1,3,4-oxadiazoles as it a privileged scaffold in modern medicinal chemistry and have the ability to inhibit growth factors, enzymes and kinases potentially involved in the attainment of cellular immortality and carcinogenesis. RESULT:In vitro MTT screening assay showed the compound 5-aminophenyl-2-butylthio-1,3,4-oxadiazole (5e) showing the highest inhibitory effect against MCF-7 cancer cell with IC50 value 10.05 ± 1.08 µM while it is much safer and less toxic on normal cell line (HEK-293). The dose-dependent treatment of MCF-7 cells with 5e resulted in inhibition of cell migration in the wound healing assay. The flow-cytometry analysis showed the cells arrested in G0/G1 phase of the cell cycle. Compound 5e induced apoptosis of MCF-7 cells was characterized using DAPI staining and Annexin V-PE/7-AAD dual binding assay. Reduction of NBT by compound 5e showed a reduced generation of ROS. Western blotting studies showed high activation of apoptotic protein Caspase3 and decrease in expression of anti-apoptotic protein BCL-2. CONCLUSION:Based on the results of in vitro studies, it could be concluded that compound 5e showed a significant inhibitory growth effect on MCF-7 cells and have the potential to be developed as lead molecule and further structural modifications may result in promising new anticancer agents.

authors

Khanam R,Ahmad K,Hejazi II,Siddique IA,Kumar V,Bhat AR,Azam A,Athar F

doi

10.1007/s00280-017-3414-6

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

1027-1042

issue

5

eissn

0344-5704

issn

1432-0843

pii

10.1007/s00280-017-3414-6

journal_volume

80

pub_type

杂志文章
  • The therapeutic efficacy of S-1 against orthotopically implanted human pleural mesothelioma cells in severe combined immunodeficient mice.

    abstract:PURPOSE:Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm. S-1 has been developed as a novel oral antineoplastic agent based on the modulation of 5-fluorouracil (5-FU) bioactivity. This study was conducted to investigate the preclinical therapeutic effect of S-1 on MPM. METHODS:We used three human MPM c...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-010-1503-x

    authors: Van TT,Hanibuchi M,Kakiuchi S,Sato S,Kuramoto T,Goto H,Mitsuhashi A,Nishioka Y,Akiyama S,Sone S

    更新日期:2011-08-01 00:00:00

  • Se-methylselenocysteine sensitizes hypoxic tumor cells to irinotecan by targeting hypoxia-inducible factor 1alpha.

    abstract:PURPOSE:Hypoxic tumor cells overexpressing hypoxia-inducible factor 1alpha (HIF-1alpha) are generally resistant to chemo/radiotherapy. We have reported that Se-methylselenocysteine (MSC) therapeutically enhances the efficacy and selectivity of irinotecan against human tumor xenografts. The aim of this study was to deli...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-009-1238-8

    authors: Chintala S,Tóth K,Cao S,Durrani FA,Vaughan MM,Jensen RL,Rustum YM

    更新日期:2010-10-01 00:00:00

  • Cancer and the tumor microenvironment: a review of an essential relationship.

    abstract:PURPOSE:The role of the microenvironment during the initiation and progression of carcinogenesis is now realized to be of critical importance, both for enhanced understanding of fundamental cancer biology, as well as exploiting this source of relatively new knowledge for improved molecular diagnostics and therapeutics....

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/s00280-008-0881-9

    authors: Mbeunkui F,Johann DJ Jr

    更新日期:2009-03-01 00:00:00

  • Stability of solutions of antineoplastic agents during preparation and storage for in vitro assays. III. Antimetabolites, tubulin-binding agents, platinum drugs, amsacrine, L-asparaginase, interferons, steroids and other miscellaneous antitumor agents.

    abstract::The stability of solutions of the antitumour antimetabolites, vinca alkaloids, podophyllotoxins, interferons, steroids and platinum drugs as well as maytansine, asparaginase, amsacrine, flavone-8-acetic acid, mitoguazone, and N-phosphonoacetyl-L-aspartate (PALA) is reviewed. Much of the published work has been done wi...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/BF00451642

    authors: Bosanquet AG

    更新日期:1989-01-01 00:00:00

  • Phase I and pharmacokinetic study of nab-paclitaxel, nanoparticle albumin-bound paclitaxel, administered weekly to Japanese patients with solid tumors and metastatic breast cancer.

    abstract:PURPOSE:We conducted phase I and tolerability studies to determine the maximum tolerated dose (MTD) and recommended dose of nab-paclitaxel when administered weekly with solid tumors and to evaluate the tolerability of weekly administration at a dose of 150 mg/m(2) with metastatic breast cancer (MBC) as a first-line the...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-011-1726-5

    authors: Ando M,Yonemori K,Katsumata N,Shimizu C,Hirata T,Yamamoto H,Hashimoto K,Yunokawa M,Tamura K,Fujiwara Y

    更新日期:2012-02-01 00:00:00

  • Multi-center clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy.

    abstract:PURPOSE:Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate response...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00280-018-3656-y

    authors: Shibuya H,Hijioka S,Sakamoto Y,Ito T,Ueda K,Komoto I,Kobayashi N,Kudo A,Yasuda H,Miyake H,Arita J,Kiritani S,Ikeda M,Imaoka H,Ueno M,Kobayashi S,Furuta M,Nagashio Y,Murohisa G,Aoki T,Matsumoto S,Motoya M,Azemo

    更新日期:2018-10-01 00:00:00

  • Phase I and pharmacokinetic study of weekly NV06 (Phenoxodiol), a novel isoflav-3-ene, in patients with advanced cancer.

    abstract:BACKGROUND:We wished to define the maximum tolerated dose (MTD), toxicity, and pharmacokinetics of the novel isoflav-3-ene, NV06 (Phenoxodioltrade mark), a compound with a diphenolic structure related chemically and biologically to genistein and flavopiridol. PATIENTS AND METHODS:Twenty-one patients with advanced canc...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-006-0189-6

    authors: de Souza PL,Liauw W,Links M,Pirabhahar S,Kelly G,Howes LG

    更新日期:2006-10-01 00:00:00

  • Analysis of gastric cancer with cDNA microarray.

    abstract::Recent advances in cDNA microarray techniques have enabled us to study the expression of many genes simultaneously. As gastric cancer remains one of the most common cancers in Japan, we studied gene expression profiles in gastric cancer by cDNA microarray analysis to determine if it would be clinically useful. We demo...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-004-0882-2

    authors: Haraguchi N,Inoue H,Mimori K,Tanaka F,Utsunomiya T,Yoshikawa K,Mori M

    更新日期:2004-09-01 00:00:00

  • Phase II trial of induction chemotherapy of pemetrexed plus split-dose cisplatin followed by pemetrexed maintenance for untreated non-squamous non-small-cell lung cancer.

    abstract:PURPOSE:We conducted a phase II trial to evaluate the efficacy and safety of induction chemotherapy of pemetrexed plus split-dose cisplatin followed by pemetrexed maintenance for advanced non-squamous non-small-cell lung cancer (NSCLC). METHODS:Patients with advanced or recurrent untreated non-squamous NSCLC received ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s00280-018-3598-4

    authors: Koba T,Minami S,Nishijima-Futami Y,Masuhiro K,Kimura H,Futami S,Yaga M,Mori M,Kagawa H,Uenami T,Kohmo S,Otsuka T,Yamamoto S,Komuta K,Kijima T

    更新日期:2018-07-01 00:00:00

  • Successful treatment of a patient with acute nonlymphoblastic leukemia (ANLL) and anthracycline cardiomyopathy with 4' (9-acridinylamino) methanesulfon-m-anisidide (AMSA).

    abstract::A patient with acute nonlymphoblastic leukemia in relapse and anthracycline cardiomyopathy was treated with AMSA in combination with cytosine arabinoside and thioguanine (AAT). Induction of remission was accomplished after one course of therapy without development of congestive heart failure. Radionuclide studies done...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00257232

    authors: Fanucchi MP,Arlin ZA

    更新日期:1982-12-01 00:00:00

  • Enhancing the anticancer efficacy of camptothecin using biotinylated poly(ethylene glycol) conjugates in sensitive and multidrug-resistant human ovarian carcinoma cells.

    abstract:BACKGROUND:Camptothecin (CPT) is an anticancer agent that kills cells by converting DNA topoisomerase I into a DNA-damaging agent. Although CPT and its derivatives are now being used to treat tumors in a variety of clinical protocols, the low water solubility of the drug and its unique pharmacodynamics and reactivity i...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-002-0463-1

    authors: Minko T,Paranjpe PV,Qiu B,Lalloo A,Won R,Stein S,Sinko PJ

    更新日期:2002-08-01 00:00:00

  • Direct evaluation of intracellular accumulation of free and polymer-bound anthracyclines.

    abstract::Nanoparticulate carriers of anthracyclines are being developed with the aim of improving the pharmacokinetic or pharmacodynamic behavior of these drugs. To understand how the drug reaches its nuclear targets, we have developed two methods that allow the quantification of the interaction between an anthracycline and ce...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00686835

    authors: Bogush T,Smirnova G,Shubina I,Syrkin A,Robert J

    更新日期:1995-01-01 00:00:00

  • A semimechanistic-physiologic population pharmacokinetic/pharmacodynamic model for neutropenia following pemetrexed therapy.

    abstract:PURPOSE:The objectives of these analyses were to (1) develop a semimechanistic-physiologic population pharmacokinetic/pharmacodynamic (PK/PD) model to describe neutropenic response to pemetrexed and to (2) identify influential covariates with respect to pharmacodynamic response. PATIENTS AND METHODS:Data from 279 pati...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-005-0077-5

    authors: Latz JE,Karlsson MO,Rusthoven JJ,Ghosh A,Johnson RD

    更新日期:2006-04-01 00:00:00

  • Chemotherapy in the management of invasive bladder cancer. A review.

    abstract::In this review of the management of invasive carcinoma of the bladder the results of primary and systemic therapies are evaluated in the light of the natural history of the disease. The clinical and pathological causes of treatment failure are assessed in an attempt to identify new approaches that may be used in the f...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审

    doi:10.1007/BF00254978

    authors: Bush H,Thatcher N,Barnard R

    更新日期:1979-01-01 00:00:00

  • Pharmacokinetic study of fludarabine phosphate (NSC 312887).

    abstract::Characterization of the pharmacokinetics of 2-FLAA has been completed in seven patients receiving 18 or 25 mg/m2 daily X 5 of 2-FLAMP over 30 min. Assuming 2-FLAMP was instantaneously converted to 2-FLAA, the plasma levels of 2-FLAA declined in a biexponential fashion. Computer fitting of the plasma concentration-time...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00256699

    authors: Hersh MR,Kuhn JG,Phillips JL,Clark G,Ludden TM,Von Hoff DD

    更新日期:1986-01-01 00:00:00

  • Induction of remission in acute promyelocytic leukemia with mitoxantrone.

    abstract::Two patients with acute promyelocytic leukemia in first relapse received mitoxantrone 12 mg/m2/day for 5 days. Both patients received IV heparin with replacement of platelets and coagulation factors for control of disseminated intravascular coagulopathy. Both have achieved a complete remission after one course of trea...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00552732

    authors: Mittelman A,Rieber E,Friedland ML,Arlin ZA

    更新日期:1985-01-01 00:00:00

  • Pharmacokinetics of high-dose intravenous melphalan in children and adults with forced diuresis. Report in 26 cases.

    abstract::The pharmacokinetic parameters of the alkylating agent melphalan were determined in 15 children and 11 adults with advanced malignant solid tumors. High IV bolus doses of 140 mg/m2 were given under standard hyperhydration conditions and followed by autologous bone marrow grafting. In all cases the time-concentration c...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00293997

    authors: Ardiet C,Tranchand B,Biron P,Rebattu P,Philip T

    更新日期:1986-01-01 00:00:00

  • Studies on the mechanism of cytotoxicity of 3-deazaguanosine in human cancer cells.

    abstract::The mechanism of toxicity of 3-deazaguanosine was studied in a number of human tumor cell lines by determination of the effects of various purine compounds on the growth of the cells in the presence of the drug and by studies of the effects of 3-deazaguanosine on the metabolism of radiolabeled precursors in these cell...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00257296

    authors: Page T,Jacobsen SJ,Smejkal RM,Scheele J,Nyhan WL,Mangum JH,Robins RK

    更新日期:1985-01-01 00:00:00

  • Pharmacokinetics of abiraterone in healthy Japanese men: dose-proportionality and effect of food timing.

    abstract:PURPOSE:Abiraterone acetate (AA) was recently approved for castration-resistant prostate cancer in Japan. Two phase 1 studies were conducted to assess the pharmacokinetics of abiraterone after single-dose administration in Japanese healthy men and to evaluate the effects of food timing on abiraterone pharmacokinetics a...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1007/s00280-014-2616-4

    authors: Inoue K,Shishido A,Vaccaro N,Jiao J,Stieltjes H,Bernard A,Yu M,Chien C

    更新日期:2015-01-01 00:00:00

  • Clinical pharmacology of UCN-01: initial observations and comparison to preclinical models.

    abstract::UCN-01 (7-hydroxystaurosporine; NSC 638850) is a protein kinase antagonist selected for clinical trial based in part on evidence of efficacy in a preclinical renal carcinoma xenograft model. Schedule studies and in vitro studies suggested that a 72-h continuous infusion would be appropriate. In rats and dogs, maximum ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1007/s002800051080

    authors: Sausville EA,Lush RD,Headlee D,Smith AC,Figg WD,Arbuck SG,Senderowicz AM,Fuse E,Tanii H,Kuwabara T,Kobayashi S

    更新日期:1998-01-01 00:00:00

  • Effects of pemetrexed, gefitinib, and their combination on human colorectal cancer cells.

    abstract:PURPOSE:The study investigated the effects of pemetrexed, gefitinib, and their combination on human colorectal cancer cells. METHODS:Six human colorectal cancer cells were exposed to pemetrexed, gefitinib, and their combination. Antitumor effects were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium br...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-013-2251-5

    authors: Zhang G,Xie X,Liu T,Yang J,Jiao S

    更新日期:2013-10-01 00:00:00

  • Comparison of the efficacy of tropisetron versus a metoclopramide cocktail based on the intensity of cisplatin-induced emesis.

    abstract::Cisplatin-induced emesis is one of the most feared side effects in cancer treatment. High-dose metoclopramide may prevent only 30-40% of cases of acute emesis. Investigations to test the efficacy of new antiemetics are mandatory. We compared the efficacy, toxicity, and patients' preference for tropisetron, a new 5-hyd...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1007/BF00688329

    authors: Chang TC,Hsieh F,Lai CH,Tseng CJ,Cheng HH,Li CL,Michael BJ,Soong YK

    更新日期:1996-01-01 00:00:00

  • The role of preoperative intra-arterial doxorubicin chemotherapy in combination with low-dose irradiation for bladder cancer.

    abstract::Twenty patients with bladder cancer (T1, 3 patients; T2, 6 patients; T3, 8 patients; T4a, 3 patients) were preoperatively treated with intra-arterial doxorubicin chemotherapy in combination with low-dose irradiation. The originally scheduled operations were as follows: total cystectomy in 16 patients (T1 + cis, 1 pati...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00262477

    authors: Uyama T,Moriwaki S,Yokozeki A,Kitada K,Higa I,Shiotsu T,Fujita J

    更新日期:1987-01-01 00:00:00

  • Combined-modality treatment of inflammatory breast carcinoma: twenty years of experience at M. D. Anderson Cancer Center.

    abstract:PURPOSE:To review the 20 years of experience at M. D. Anderson Cancer Center with a combined-modality approach against inflammatory breast carcinoma. PATIENTS AND METHODS:A total of 178 patients with inflammatory breast carcinoma were treated in the past 20 years at M. D. Anderson Cancer Center by a combined-modality ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800050664

    authors: Ueno NT,Buzdar AU,Singletary SE,Ames FC,McNeese MD,Holmes FA,Theriault RL,Strom EA,Wasaff BJ,Asmar L,Frye D,Hortobagyi GN

    更新日期:1997-01-01 00:00:00

  • Ineligibility for the PACIFIC trial in unresectable stage III non-small cell lung cancer patients.

    abstract:PURPOSE:Recently, based on results of the PACIFIC trial, durvalumab after chemoradiotherapy (CRT) became the standard therapy for unresectable stage III non-small cell lung cancer (NSCLC). However, in the PACIFIC trial, patients were recruited and randomized after CRT, and certain patients were considered ineligible af...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-019-03885-4

    authors: Hosoya K,Fujimoto D,Kawachi H,Sato Y,Kogo M,Nagata K,Nakagawa A,Tachikawa R,Hiraoka S,Kokubo M,Tomii K

    更新日期:2019-08-01 00:00:00

  • Chemomodulation of drugs involved in multidrug resistance in chronic lymphatic leukemia of the B-cell type.

    abstract::Reduced drug accumulation may be one reason for intrinsic drug resistance in chronic lymphatic leukemia of the B-cell type (B-CLL). Immunophenotyped leukemic human B-cells from 38 cases of B-CLL were characterized for P-glycoprotein (PGP) content. In all, 30 cases of B-CLL were additionally analyzed for further parame...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00686038

    authors: Reichle A,Diddens H,Altmayr F,Rastetter J,Andreesen R

    更新日期:1994-01-01 00:00:00

  • The combi-targeting concept: a novel 3,3-disubstituted nitrosourea with EGFR tyrosine kinase inhibitory properties.

    abstract:PURPOSE:To study the dual mechanism of action of FD137, a 3,3-disubstituted nitrosourea designed to block signaling mediated by the epidermal growth factor receptor (EGFR) on its own and to be hydrolyzed to an inhibitor of EGFR plus a DNA-damaging species. MATERIALS AND METHODS:HPLC was used to determine the half-life...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-002-0524-5

    authors: Qiu Q,Dudouit F,Matheson SL,Brahimi F,Banerjee R,McNamee JP,Jean-Claude BJ

    更新日期:2003-01-01 00:00:00

  • Effect of amifostine on the cytotoxicity of daunorubicin and daunoxome in tumor and normal cells.

    abstract::Anthracyclines are powerful cytotoxic agents, used as first-line treatment of leukemias and many other tumors, but host-tissue toxicity is their main dose-limiting factor. However, their therapeutic effects depend not only on the toxicity, hence on the dose, but also on drug resistance. Among the mechanisms that can a...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s00280-005-0043-2

    authors: Michelutti A,Stocchi R,Candoni A,Tiribelli M,Calistri E,Russo D,Fanin R,Damiani D

    更新日期:2006-04-01 00:00:00

  • Relationship between pharmacokinetics of unchanged cisplatin and nephrotoxicity after intravenous infusions of cisplatin to cancer patients.

    abstract:PURPOSE:The relationships between pharmacokinetic parameters of unchanged cisplatin (CDDP) and several markers for nephrotoxicity after CDDP infusion (80 mg/m2) over 2 and 4 h were quantitated in patients with various cancers (lung, stomach and colon cancers and mediastinal tumor). METHODS:Plasma and urinary levels of...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/s002800050548

    authors: Nagai N,Kinoshita M,Ogata H,Tsujino D,Wada Y,Someya K,Ohno T,Masuhara K,Tanaka Y,Kato K,Nagai H,Yokoyama A,Kurita Y

    更新日期:1996-01-01 00:00:00

  • Prognosis after hepatic resection in patients with hepatocellular carcinoma, estimated on the basis of the morphometric indices.

    abstract::To determine whether the morphometric indices of hepatocellular carcinoma (HCC) correlated with the prognoses, the microscopic morphometric values for 84 HCC cases treated by hepatic resection were studied using an image analyzer in relation to the survival rate and the gross classification. The mean survival time (MS...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章

    doi:10.1007/BF00686663

    authors: Kawai Y,Takeshige K,Nunome M,Kuroda H,Suzuki H,Banno K,Koide T,Kobayashi H,Owa Y,Koike A

    更新日期:1994-01-01 00:00:00