Abstract:
:Emerging evidence suggests that autophagic modulators have therapeutic potential. This study aims to identify novel autophagic inducers from traditional Chinese medicinal herbs as potential antitumor agents. Using an image-based screen and bioactivity-guided purification, we identified alisol B 23-acetate, alisol A 24-acetate, and alisol B from the rhizome of Alisma orientale as novel inducers of autophagy, with alisol B being the most potent natural product. Across several cancer cell lines, we showed that alisol B-treated cells displayed an increase of autophagic flux and formation of autophagosomes, leading to cell cycle arrest at the G(1) phase and cell death. Alisol B induced calcium mobilization from internal stores, leading to autophagy through the activation of the CaMKK-AMPK-mammalian target of rapamycin pathway. Moreover, the disruption of calcium homeostasis induces endoplasmic reticulum stress and unfolded protein responses in alisol B-treated cells, leading to apoptotic cell death. Finally, by computational virtual docking analysis and biochemical assays, we showed that the molecular target of alisol B is the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase. This study provides detailed insights into the cytotoxic mechanism of a novel antitumor compound.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Law BY,Wang M,Ma DL,Al-Mousa F,Michelangeli F,Cheng SH,Ng MH,To KF,Mok AY,Ko RY,Lam SK,Chen F,Che CM,Chiu P,Ko BCdoi
10.1158/1535-7163.MCT-09-0700subject
Has Abstractpub_date
2010-03-01 00:00:00pages
718-30issue
3eissn
1535-7163issn
1538-8514pii
1535-7163.MCT-09-0700journal_volume
9pub_type
杂志文章abstract:UNLABELLED:Multiple myeloma (MM) is a malignancy of clonal B-cells that accounts for 10% of all hematologic malignancies. We have shown previously that a novel purine analogue, 8-chloro-adenosine, has significant activity for MM in preclinical studies. OBJECTIVE:Using MM cell lines, we investigated the molecular mecha...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2004-11-01 00:00:00
abstract::To determine the efficacy of a novel and safer (for gastrointestinal tract) aspirin (aspirin-PC) in preclinical models of ovarian cancer, in vitro dose-response studies were performed to compare the growth-inhibitory effect of aspirin-PC versus aspirin on three human (A2780, SKOV3ip1, and HeyA8) and a mouse (ID8) ovar...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-16-0074
更新日期:2016-12-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-0179
更新日期:2019-03-01 00:00:00
abstract::Head and neck squamous cell carcinoma (HNSCC) is characterized by epidermal growth factor receptor (EGFR) overexpression, where EGFR levels correlate with survival. To date, EGFR targeting has shown limited antitumor effects in head and neck cancer when administrated as monotherapy. We previously identified a gastrin-...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0678
更新日期:2007-04-01 00:00:00
abstract::Tivantinib (ARQ197) was first reported as a highly selective inhibitor of c-MET and is currently being investigated in a phase III clinical trial. However, as recently reported by us and another group, tivantinib showed cytotoxic activity independent of cellular c-MET status and also disrupted microtubule dynamics. To...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-14-0462
更新日期:2014-12-01 00:00:00
abstract::Isodon diterpenoids have received considerable phytochemical and biological attention for their strong antitumor activity with low toxicity. In this study, ExcisaninA, a diterpenoid compound purified from Isodon MacrocalyxinD, was tested on human Hep3B and MDA-MB-453 cell lines and Hep3B xenograft models. The results ...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-1080
更新日期:2009-04-01 00:00:00
abstract::The standard treatment for most advanced cancers is multidrug therapy. Unfortunately, combinations in the clinic often do not perform as predicted. Therefore, to complement identifying rational drug combinations based on biological assumptions, we hypothesized that a functional screen of drug combinations, without lim...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-0937
更新日期:2009-03-01 00:00:00
abstract::The protein kinase family represents an enormous opportunity for drug development. However, the current limitation in structural diversity of kinase inhibitors has complicated efforts to identify effective treatments of diseases that involve protein kinase signaling pathways. We have identified a new structural class ...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2004-01-01 00:00:00
abstract::Cryptophycin 52 (LY355703) is a potent antiproliferative analogue of the marine natural product cryptophycin 1. It has been shown to have a broad range of antitumor activity against human tumor xenografts and murine tumors including tumors resistant to Taxol and Adriamycin. Its mechanism of action involves arresting c...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2004-09-01 00:00:00
abstract::The p53 inactivation caused by aberrant expression of its major regulators (e.g., MDM2 and MDMX) contributes to the genesis of a large number of human cancers. Recent studies have shown that restoration of p53 activity by counteracting p53 repressors is a promising anticancer strategy. Although agents (e.g., nutlin-3a...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-10-0581
更新日期:2011-01-01 00:00:00
abstract::In the present work, we have investigated the antitumor activity of 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) on aggressive small cell lung cancer. NBDHEX not only is cytotoxic toward the parental small cell lung cancer H69 cell line (LC(50) of 2.3 +/- 0.6 micromol/L) but also overcomes the multidrug re...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-0487
更新日期:2008-02-01 00:00:00
abstract::Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion found in a subset of patients with non-small cell lung cancer (NSCLC). While in clinical trials, PF02341066 has shown a significan...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-12-0868
更新日期:2013-05-01 00:00:00
abstract::Urokinase plasminogen activator (uPA) is a tumor-specific protease highly expressed in several types of solid tumors and rarely present on normal cells under physiologic conditions. Due to its high expression on metastatic tumors, several different strategies have been used to target the urokinase system. These have m...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0315
更新日期:2006-10-01 00:00:00
abstract::Resistance to antiandrogen drugs, like MDV3100, occurs in patients with castration-resistant prostate cancer (CRPC). Thus, preventing or treating antiandrogen resistance is a major clinical challenge. We identified a novel antiandrogen, Compound 30, and compared its efficacy with MDV3100. We found that Compound 30 inh...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-12-0798
更新日期:2013-05-01 00:00:00
abstract::Long noncoding RNAs (lncRNA) have been found to play critical roles in tumorigenesis and the development of various cancers, including hepatocellular carcinoma (HCC). Metastasis associated with lung adenocarcinoma transcript-1 (MALAT1) has been identified as an oncogene and prognostic biomarker in HCC. Here, we demons...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-19-0203
更新日期:2020-05-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-05-0168
更新日期:2005-09-01 00:00:00
abstract::2-Amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx-1) has been developed as a novel phenoxazine derivative having an anticancer activity on a variety of cancer cell lines as well as transplanted tumors in mice with minimal toxicity to normal cells. We examined the effects of Phx-1 on Jurkat cells, a ...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-05-0067
更新日期:2005-07-01 00:00:00
abstract::High Mycoplasma infection in gastric cancer tissues suggests a possible association between Mycoplasma infection and tumorigenesis. By using human gastric cancer cells AGS and mouse melanoma cells B16F10 stably expressing p37, the major immunogen of Mycoplasma hyorhinis, we found that p37 enhanced cell motility, migra...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-2191
更新日期:2008-03-01 00:00:00
abstract::Luteolin, a common dietary flavonoid, has been found to have antitumor properties and therefore poses special interest for the development of preventive and/or therapeutic agent for cancers. E-cadherin, a marker of epithelial cells, mediates cell-cell adhesion. Decreased expression of E-cadherin results in a loss of c...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-09-0191
更新日期:2009-06-01 00:00:00
abstract::Improved survival for patients with head and neck cancers (HNC) with recurrent and metastatic disease warrants that cancer therapy is specific, with protected delivery of the therapeutic agent to primary and metastatic cancer cells. A further objective should be that downregulation of the intracellular therapy target ...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-14-0166
更新日期:2014-08-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-0067
更新日期:2019-03-01 00:00:00
abstract::Advanced and hormone-refractory prostate cancer has long been considered as a chemoresistant disease. Recently, it was found that 14-3-3sigma expression increases as prostate tumor progresses, and that 14-3-3sigma contributes significantly to drug resistance in breast cancers. We, thus, hypothesized that advanced and ...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-05-0393
更新日期:2006-04-01 00:00:00
abstract::GA101 is a novel glycoengineered Type II CD20 monoclonal antibody. When compared with rituximab, it mediates less complement-dependent cytotoxicity (CDC). As expected for a Type II antibody, GA101 appears not to act through CDC and is more potent than the Type I antibody rituximab in inducing cell death via nonclassic...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-10-0385
更新日期:2011-01-01 00:00:00
abstract::Alpha-emitters can be pharmacologically delivered for irradiation of single cancer cells, but cellular lethality could be further enhanced by targeting alpha-emitters directly to the nucleus. PARP-1 is a druggable protein in the nucleus that is overexpressed in neuroblastoma compared with normal tissues and is associa...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-0837
更新日期:2019-07-01 00:00:00
abstract::Wee1 is a critical component of the G(2)-M cell-cycle checkpoint control and mediates cell-cycle arrest by regulating the phosphorylation of CDC2. Inhibition of Wee1 by a selective small molecule inhibitor MK1775 can abrogate G(2)-M checkpoint, resulting in premature mitotic entry and cell death. MK1775 has recently b...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-11-0529
更新日期:2012-01-01 00:00:00
abstract::Tolfenamic acid (TA) is a nonsteroidal anti-inflammatory drug that inhibits pancreatic cancer cell and tumor growth through decreasing expression of specificity protein (Sp) transcription factors. TA also inhibits growth of erbB2-overexpressing BT474 and SKBR3 breast cancer cells; however, in contrast to pancreatic ca...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-08-1097
更新日期:2009-05-01 00:00:00
abstract::AMAD, an emodin azide methyl anthraquinone derivative, was extracted from the nature giant knotweed rhizome of traditional Chinese herbs. Here, we investigated the anticancer activities and signaling pathways implicated in AMAD-induced apoptosis in human breast cancer cell lines MDA-MB-453 and human lung adenocarcinom...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-2362
更新日期:2008-06-01 00:00:00
abstract::Aminoflavone (AF), a clinically investigational novel anticancer agent, requires sequential metabolic activation by CYP1A1 and SULT1A1 to exert its antitumor activities. The purpose of this study was to determine the functional significance of common polymorphisms of human CYP1A1 and SULT1A1 on the metabolism and cyto...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-10-0597
更新日期:2010-10-01 00:00:00
abstract::Neuroblastoma is the most common extracranial solid malignancy in the pediatric population, accounting for over 9% of all cancer-related deaths in children. Autophagy is a cell self-protective mechanism that promotes tumor cell growth and survival, making it an attractive target for treating cancer. However, the role ...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-0176
更新日期:2018-11-01 00:00:00
abstract::We investigated integrin-linked kinase (ILK), a focal adhesion serine-threonine protein kinase, as a new molecular target for treating anaplastic thyroid cancer. ILK mediates cell growth and survival signals and is overexpressed in a number of cancers. Therefore, we hypothesized that inhibition of ILK leads to growth ...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-05-0078
更新日期:2005-08-01 00:00:00