☆ 4.7 Article

A Novel Resveratrol Based Tubulin Inhibitor Induces Mitotic Arrest and Activates Apoptosis in Cancer Cells

SCIENTIFIC REPORTS (2016)

期刊

SCIENTIFIC REPORTS

卷 6, 期 -, 页码 -

出版社

NATURE PUBLISHING GROUP

DOI: 10.1038/srep34653

关键词

-

类别

Multidisciplinary Sciences

资金

IISc-DBT partnership programme [DBT/BF/PR/INS/2011-12/IISc]
DST postdoctoral fellowship programme, India
SRF, CSIR, India

向作者/读者索取更多资源

Protocol

Reagent

摘要

Resveratrol is one of the most widely studied bioactive plant polyphenols which possesses anticancer properties. Previously we have reported synthesis, characterization and identification of a novel resveratrol analog, SS28. In the present study, we show that SS28 induced cytotoxicity in several cancer cell lines ex vivo with an IC50 value of 3-5 mu M. Mechanistic evaluation of effect of SS28 in non-small cell lung cancer cell line (A549) and T-cell leukemic cell line (CEM) showed that it inhibited Tubulin polymerization during cell division to cause cell cycle arrest at G2/M phase of the cell cycle at 12-18 h time period. Immunofluorescence studies confirmed the mitotic arrest upon treatment with SS28. Besides, we show that SS28 binds to Tubulin with a dissociation constant of 0.414 +/- 0.11 mu M. Further, SS28 treatment resulted in loss of mitochondrial membrane potential, activation of Caspase 9 and Caspase 3, leading to PARP-1 cleavage and finally cell death via intrinsic pathway of apoptosis. Importantly, treatment with SS28 resulted in regression of tumor in mice. Hence, our study reveals the antiproliferative activity of SS28 by disrupting microtubule dynamics by binding to its cellular target Tubulin and its potential to be developed as an anticancer molecule.

作者

我是这篇论文的作者

点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7

评分不足

次要评分

新颖性

-

重要性

-

科学严谨性

-

评价这篇论文

推荐

Article Chemistry, Medicinal

RS6077 induces mitotic arrest and selectively activates cell death in human cancer cell lines and in a lymphoma tumor in vivo

Jessica Sebastiani, Michela Puxeddu, Marianna Nalli, Ruoli Bai, Ludovica Altieri, Paola Rovella, Eugenio Gaudio, Daniela Trisciuoglio, Filippo Spriano, Patrizia Lavia, Cinzia Fionda, Domiziana Masci, Andrea Urbani, Chiara Bigogno, Giulio Dondio, Ernest Hamel, Francesco Bertoni, Romano Silvestri, Giuseppe La Regina

Summary: We synthesized a new tubulin polymerization inhibitor, RS6077, which inhibited the growth of multiple cancer cell lines without affecting non-transformed cells. It induced G2/M phase arrest in both transformed and non-transformed cells, but showed selective induction of cell death in transformed cells that fail to complete mitosis. RS6077 also inhibited the growth of a lymphoma xenograft model and demonstrated good metabolic stability.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2023)

添加到收藏夹

Article Pharmacology & Pharmacy

Dual Inhibition of γ-Tubulin and Plk1 Induces Mitotic Cell Death

Haruna Ebisu, Kana Shintani, Takumi Chinen, Yoko Nagumo, Shuya Shioda, Taisei Hatanaka, Akira Sakakura, Ichiro Hayakawa, Hideo Kigoshi, Takeo Usui

Summary: The study verified the antitumor activity of a specific γ-tubulin inhibitor, gatastatin, which showed weaker cytotoxicity compared to conventional microtubule inhibitors. Screening revealed that the Plk1 inhibitor, BI 2536, significantly increased the cytotoxicity of gatastatin, leading to cell cycle arrest at mitosis with abnormal spindles and mitotic cell death. Co-treatment with Plk1 and γ-tubulin inhibitors may offer a novel approach to cancer chemotherapy.

FRONTIERS IN PHARMACOLOGY (2021)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of novel trimethoxyphenylbenzo[d]oxazoles as dual tubulin/PDE4 inhibitors capable of inducing apoptosis at G2/M phase arrest in glioma and lung cancer cells

Jie Liu, Wan Ye, Jiang-Ping Xu, Hai-Tao Wang, Xiao-Fang Li, Wen-Ya Wang, Zhong-Zhen Zhou

Summary: Novel dual PDE4/tubulin inhibitor 4r, derived from trimethoxyphenylbenzo[d]oxazoles, exhibited satisfactory antiproliferative activities against glioma and lung cancer cells by inducing apoptosis and disrupting the microtubule network. Its mechanism of action involved down-regulation of cyclin B1 and its upstream regulator gene cdc25C.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

添加到收藏夹

Article Cell Biology

Benzimidazole carbamate induces cytotoxicity in breast cancer cells via two distinct cell death mechanisms

Brendan T. Graff, Chitra Palanivel, Christopher B. Jenkins, Janina Baranowska-Kortylewicz, Ying Yan

Summary: Metastatic breast cancer (mBC) is responsible for >90% of breast cancer-related deaths. The effectiveness of microtubule-targeting agents (MTAs) in mBC treatment is limited by primary or acquired resistance. This study evaluated the potential of methyl N-(6-benzoyl-1H-benzimidazol-2-yl)carbamate (BCar) as a novel MTA for MTA-resistant mBC. The results showed that BCar selectively killed breast cancer cells and had a wider therapeutic window compared to clinical MTAs docetaxel and vincristine.

CELL DEATH DISCOVERY (2023)

添加到收藏夹

Article Oncology

Novel colchicine derivative CR42-24 demonstrates potent anti-tumor activity in urothelial carcinoma

Clayton J. Bell, Kyle G. Potts, Mary M. Hitt, Desmond Pink, Jack A. Tuszynski, John D. Lewis

Summary: The novel colchicine derivative CR42-24 has shown selective cytotoxicity against various cancer cell lines, with high activity in bladder cancer cell lines. Monotherapy with CR42-24 in an aggressive urothelial carcinoma xenograft model effectively controls large tumors. The combination of CR42-24 with standard chemotherapies gemcitabine and cisplatin demonstrates high synergistic effects, increasing its potential as a novel treatment for urothelial carcinoma.

CANCER LETTERS (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

A novel translation inhibitor, mersicarpine, inhibits S-phase progression and induces apoptosis in HL60 cells

Tomoko Shiobara, Yoko Nagumo, Rie Nakajima, Tohru Fukuyama, Satoshi Yokoshima, Takeo Usui

Summary: Mersicarpine can reversibly arrest the cell cycle progression in S-phase and induce apoptosis in human leukemia cell line HL60. It also inhibits protein synthesis, making it a novel translation inhibitor.

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

Novel bioactive hybrid Celecoxib-HDAC Inhibitor, induces apoptosis in human acute lymphoblastic leukemia cells

Jing Liu, Li Zhang, Ling Guo, Yan Zeng, Qulian Guo, Chunmei Yang, Jian Shu, Wenjun Liu, Lu Yang

Summary: Compound 11, a hybrid Celecoxib-HDAC inhibitor, exhibited significant induction of cell death and inhibition of cell growth in NALM6 cells, making it a potential chemotherapeutic agent for ALL.

BIOORGANIC & MEDICINAL CHEMISTRY (2022)

添加到收藏夹

Article Pharmacology & Pharmacy

IMB5476, a novel microtubule inhibitor, induces mitotic catastrophe and overcomes multidrug resistance in tumors

Yan-Bo Zheng, Yan-Qun Dong, Shu-Yi Si, Yong-Su Zhen, Jian-Hua Gong

Summary: IMB5476, a novel nitrobenzoate microtubule inhibitor, exhibits increased aqueous solubility. It disrupts microtubule networks in cells, causing cell cycle arrest and inducing cell death through mitotic catastrophe and apoptosis. IMB5476 also inhibits angiogenesis and overcomes multidrug resistance.

EUROPEAN JOURNAL OF PHARMACOLOGY (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

MHY2245, a Sirtuin Inhibitor, Induces Cell Cycle Arrest and Apoptosis in HCT116 Human Colorectal Cancer Cells

Yong Jung Kang, Jung Yoon Jang, Young Hoon Kwon, Jun Ho Lee, Sanggwon Lee, Yujin Park, Young-Suk Jung, Eunok Im, Hyung Ryong Moon, Hae Young Chung, Nam Deuk Kim

Summary: MHY2245 induces cell cycle arrest through DNA damage-induced p53 activation and apoptosis via caspase activation, showing anticancer effects associated with DNA damage response.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

添加到收藏夹

Article Multidisciplinary Sciences

Sulforaphane induces S-phase arrest and apoptosis via p53-dependent manner in gastric cancer cells

Yuan Wang, Huazhang Wu, Nannan Dong, Xu Su, Mingxiu Duan, Yaqin Wei, Jun Wei, Gaofeng Liu, Qingjie Peng, Yunli Zhao

Summary: The study demonstrated that SFN impairs colony-forming ability in GC cells, suppresses cell proliferation by arresting cell cycle at S phase, enhances cell apoptosis, and upregulates p53, p21 while downregulating CDK2 expression, suggesting a potential therapeutic application of SFN in GC treatment and prevention.

SCIENTIFIC REPORTS (2021)

添加到收藏夹

Article Chemistry, Medicinal

Novel combretastatin A-4 derivative containing aminophosphonates as dual inhibitors of tubulin and matrix metalloproteinases for lung cancer treatment

Xiaochao Huang, Yuanhang Chen, Wentian Zhong, Zhikun Liu, Haijiang Zhang, Bin Zhang, Hengshan Wang

Summary: In this study, sixteen novel conjugates containing tubulin inhibitor and matrix metalloproteinase inhibitor were synthesized and evaluated for their activity. Compound 9e showed the most potent activity against various human cancer cells, including multidrug-resistant tumor cells, and exhibited lower cytotoxicity towards normal liver cells. It strongly inhibited tubulin polymerization, induced cell apoptosis and cell cycle arrest, and displayed inhibition of cell migration and moderate activity towards MMP-2, MMP-3, and MMP-9. Moreover, it induced apoptosis via the mitochondria-dependent pathway and caused ER stress. In vivo, 9e showed significant antitumor efficacy without systemic toxicity. Overall, compound 9e is a novel and promising agent for cancer therapy, acting as a dual MMPs and tubulin inhibitor.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

The Design, Synthesis, and Biological Activities of Pyrrole-Based Carboxamides: The Novel Tubulin Inhibitors Targeting the Colchicine-Binding Site

Sergei Boichuk, Aigul Galembikova, Kirill Syuzov, Pavel Dunaev, Firuza Bikinieva, Aida Aukhadieva, Svetlana Zykova, Nazim Igidov, Ksenia Gankova, Maria Novikova, Pavel Kopnin

Summary: Novel pyrrole-based carboxamides (CAs) (CA-61 and -84) exhibit potent anti-cancer properties by interfering with microtubule network and inhibiting tubulin polymerization, leading to apoptosis in epithelial cancer cell lines.

MOLECULES (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

A novel series of benzothiazepine derivatives as tubulin polymerization inhibitors with anti-tumor potency

Bin Wang, Li-Ren Wang, Lu-Lu Liu, Wei Wang, Ruo-Jun Man, Da-Jun Zheng, Yu-Shan Deng, Yu-Shun Yang, Chen Xu, Hai-Liang Zhu

Summary: In this study, a series of diaryl benzo[b][1,4]thiazepine derivatives were synthesized and screened as tubulin polymerization inhibitors with anti-tumor potency. Among them, the hit compound D8 showed potential in inhibiting the growth of several cancer cell lines, with comparable activity to Colchicine and CA-4P. The results indicated the potential for further modification of tubulin-related anti-cancer agents and therapeutic approaches.

BIOORGANIC CHEMISTRY (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

Novel Dual PI3K/mTOR Inhibitor, Apitolisib (GDC-0980), Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells

Wioleta Justyna Omeljaniuk, Rafal Kretowski, Wioletta Ratajczak-Wrona, Ewa Jablonska, Marzanna Cechowska-Pasko

Summary: The study found that GDC-0980 can effectively inhibit the survival of human GBM cells and induce apoptosis, independent of ER stress-mediated DR5 activation. It is suggested that GDC-0980 may block the inhibitory effect on protein synthesis through inhibiting PERK expression, leading to an intensification of translation and an increase in apoptosis. Additionally, CHOP stimulates protein synthesis and increases apoptosis.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

添加到收藏夹

Article Oncology

SB226, an inhibitor of tubulin polymerization, inhibits paclitaxel-resistant melanoma growth and spontaneous metastasis

Shanshan Deng, Souvik Banerjee, Hao Chen, Satyanarayana Pochampally, Yuxi Wang, Mi-Kyung Yun, Stephen W. White, Keyur Parmar, Bernd Meibohm, Kelli L. Hartman, Zhongzhi Wu, Duane D. Miller, Wei Li

Summary: This study reports a novel inhibitor, SB226, which shows great promise for cancer therapy. Through extensive preclinical studies and in vitro/in vivo experiments, it was confirmed that SB226 has high affinity for tubulin dimers, exhibits anti-proliferative activities, inhibits tumor growth, induces apoptosis, and shows no obvious toxicity.

CANCER LETTERS (2023)

添加到收藏夹

Article Biochemistry & Molecular Biology

Synthesis, Molecular Docking and Preliminary Antileukemic Activity of 4-Methoxybenzyl Derivatives Bearing Imidazo[2,1-b][1,3,4]thiadiazole

B. Choodamani, Karla G. Cano Hernandez, Sujeet Kumar, Ann Maria Tony, Austre Y. Schiaffino Bustamante, Renato J. Aguilera, Dominique Schols, C. Gopi Mohan, Subhas S. Karki

Summary: The study synthesized 22 compounds with various substitutions on imidazo[2,1-b][1,3,4]thiadiazoles and investigated their potential cytotoxic activity in leukemia cell lines. Two compounds showed the most cytotoxic effect against leukemia cells, T-lymphocyte cells, and cervix carcinoma cells, with IC50 values ranging between 0.79 and 1.6 μM. These compounds induce apoptosis through phosphatidylserine externalization and caspase-3 activation, and binding studies showed strong interactions with the active sites of TGF-beta type I receptor kinase domain.

CHEMISTRY & BIODIVERSITY (2021)

添加到收藏夹

Article Chemistry, Physical

Synthesis, molecular docking, and preliminary cytotoxicity study of some novel 2-(naphthalen-1-yl)-methylimidazo[2,1-b][1,3,4] thiadiazoles

B. Choodamani, Sujeet Kumar, Alok Kumar Gupta, Dominique Schols, Hakan Tahtaci, Tuncay Karakurt, Satvik Kotha, B. Swapna, Ramachandra Setty, Subhas S. Karki

Summary: A series of derivatives of 2-(naphthalen-1-yl)-methyl-6-arylimidazo[2,1-b][1,3,4]thiadiazole were synthesized and studied for cytotoxicity against various cell lines. The pharmacokinetic properties of the compounds were evaluated using a prediction tool, and molecular docking studies were conducted to assess their potential as inhibitors for the EGFR protein structure. Selected compounds showed promising stability in molecular dynamics simulations.

JOURNAL OF MOLECULAR STRUCTURE (2021)

添加到收藏夹

Article Oncology

Synthesis, Anticancer Evaluation and Molecular Docking of Hexahydroquinoline Derivatives as Mcl-1 Inhibitors and Apoptosis Inducers

Nishith Teraiya, Subhas S. Karki, Ashlesha Chauhan

Summary: This study synthesized new compounds and screened them for cytotoxicity. The active compound induced apoptosis by regulating the cell cycle, inhibiting the anti-apoptotic protein Mcl-1, and activating the pro-apoptotic proteins caspase-3 and caspase-9.

ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY (2022)

添加到收藏夹

Meeting Abstract Hematology

Germline Runx1 Mutations Induce Inflammation in Hematopoietic Stem and Progenitor Cells and Predispose to Hematologic Malignancies

Mohd Hafiz Ahmad, Mahesh Hegde, Waihay J. Wong, Andrew Dunbar, Anneliese Carrascoso, Lisa J. Garett, Nayara K. Ferreira, Haibo Liu, Rui Li, Benjamin L. Eberg, Ross L. Levine, Julie Zhu, Scot A. Wolfe, Paul P. Lui, Lucio H. Castilla

BLOOD (2021)

添加到收藏夹

Article Oncology

Curcumin derivative 1, 2-bis [(3E, 5E)-3, 5-bis [(2-chlorophenyl) methylene]-4-oxo-1-piperidyl] ethane-1, 2-dione (ST03) induces mitochondria mediated apoptosis in ovarian cancer cells and inhibits tumor progression in EAC mouse model

Jinsha Koroth, Raghunandan Mahadeva, Febina Ravindran, Tanvi R. Parashar, Vinay Teja, Subhas S. Karki, Bibha Choudhary

Summary: In this study, a curcumin derivative called ST03 exhibited better bioavailability and stability compared to curcumin. ST03 demonstrated anticancer effects by inducing reactive oxygen species (ROS) and activating the intrinsic apoptotic pathway in ovarian cancer cells. ST03 also inhibited the migration of ovarian cancer cells. These findings suggest that ST03 has potential as a promising drug candidate for anticancer therapies.

TRANSLATIONAL ONCOLOGY (2022)

添加到收藏夹

Article Biology

Synthesis, in vitro cytotoxicity, molecular docking and ADME study of some indolin-2-one linked 1,2,3-triazole derivatives

Arnika Das, Giulia Greco, Sujeet Kumar, Elena Catanzaro, Rita Morigi, Alessandra Locatelli, Dominique Schols, Hakan Alici, Hakan Tahtaci, Febina Ravindran, Carmela Fimognari, Subhas S. Karki

Summary: This study focused on the synthesis of a library of 1,2,3-triazole derivatives and their screening for cytotoxicity against various cell lines. Compound 7c was identified as the most active one, inducing apoptosis in Jurkat cells through both intrinsic and extrinsic pathways and disrupting cell cycle progression. Molecular docking simulations revealed its binding to the active sites of EGFR, indicating potential for further development as a lead compound for anticancer drugs.

COMPUTATIONAL BIOLOGY AND CHEMISTRY (2022)

添加到收藏夹

Retraction Nanoscience & Nanotechnology

撤稿声明: Effects of Green Synthesised Silver Nanoparticles (ST06-AgNPs) Using Curcumin Derivative (ST06) on Human Cervical Cancer Cells (HeLa) in vitro and EAC Tumor Bearing Mice Models (Retraction of Vol 14, Pg 5257, 2019)

K. Murugesan, J. Koroth, Srinivasan Pp

INTERNATIONAL JOURNAL OF NANOMEDICINE (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

Synthesis of Novel Pyrazole-Oxindole Conjugates with Cytotoxicity in Human Cancer Cells via Apoptosis

Pravesh M. Jain, Denisse A. Gutierrez, Sujeet Kumar, Renato J. Aguilera, Subhas S. Karki

Summary: A series of pyrazole-oxindole conjugates were studied as potential cytotoxic agents. The compound 5-methyl-3-((3-(1-phenyl)-3-(p-tolyl)-1H-pyrazol-4-yl)methylene)indolin-2-one 6h showed the highest cytotoxic activity against Jurkat cells with a CC50 of 4.36 +/- 0.2 μM. Mechanistic studies revealed that 6h induced apoptosis in a dose-response manner, without generating reactive oxygen species (ROS) and altering mitochondrial health.

CHEMISTRY & BIODIVERSITY (2023)

添加到收藏夹

Article Biochemistry & Molecular Biology

A Coumarin-Imidazothiadiazole Derivative, SP11 Abrogates Tumor Growth by Targeting HSP90 and Its Client Proteins

Snehal Nirgude, M. Shahana, Febina Ravindran, Sujeet Kumar, Shivangi Sharma, Raghunandan Mahadeva, Anisha S. Mhatre, Subhas Karki, Bibha Choudhary

Summary: Despite available treatment options, blood cancer still has high mortality rate due to relapse and aggressive nature of the disease. Elevated levels of HSP90 have been associated with poor prognosis in leukemia and lymphoma. The HSP90 inhibitor, SP11, demonstrated cytotoxicity against leukemic cells and induced cell death through apoptosis, while having minimal effect on normal cells. SP11 also showed potential in reducing tumor burden in mouse models without apparent toxicity.

MOLECULES (2023)

添加到收藏夹

Article Pharmacology & Pharmacy

Three novel piperidones exhibit tumor-selective cytotoxicity on leukemia cells via protein degradation and stress-mediated mechanisms

Lisett Contreras, Stephanie Medina, Austre Y. Schiaffino Bustamante, Edgar A. Borrego, Carlos A. Valenzuela, Umashankar Das, Subhas S. Karki, Jonathan R. Dimmock, Renato J. Aguilera

Summary: Compounds P3, P4, and P5 show promising potential as anticancer drug candidates, demonstrated by their strong cytotoxic effects, activation of the intrinsic pathway of apoptosis, and typical characteristics of proteasome inhibitors.

PHARMACOLOGICAL REPORTS (2022)

添加到收藏夹

Article Multidisciplinary Sciences

Synthesis, in silico ADME, molecular docking and in vitro cytotoxicity evaluation of stilbene linked 1,2,3-triazoles

Arnika Das, Sujeet Kumar, Leentje Persoons, Dirk Daelemans, Dominique Schols, Hakan Alici, Hakan Tahtaci, Subhas S. Karki

Summary: A series of novel (E)-1-benzyl-4-((4-styrylphenoxy)methyl)-1H-1,2,3-triazole compounds were synthesized using Wittig reaction and evaluated for cytotoxicity. Some compounds exhibited moderate cytotoxicity against human cancer cell lines, while resveratrol linked compounds were more sensitive to leukemia and lymphoma cell lines.

HELIYON (2021)

添加到收藏夹

暂无数据

© Peeref 2019-2024. All rights reserved.