Chetomin induces apoptosis in human triple-negative breast cancer cells by promoting calcium overload and mitochondrial dysfunction.

Published on Jan 8, 2018in Biochemical and Biophysical Research Communications2.985
· DOI :10.1016/J.BBRC.2017.11.199
Jayant Dewangan9
Estimated H-index: 9
(Central Drug Research Institute),
Sonal Srivastava7
Estimated H-index: 7
(Central Drug Research Institute)
+ 3 AuthorsSrikanta Kumar Rath13
Estimated H-index: 13
(Central Drug Research Institute)
Abstract Human triple-negative breast cancer (TNBC) is poorly diagnosed and unresponsive to conventional hormone therapy. Chetomin (CHET), a fungal metabolite synthesized by Chaetomium cochliodes, has been reported as a promising anticancer and antiangiogenic agent but the complete molecular mechanism of its anticancer potential remains to be elucidated. In our study, we explored the anti-neoplastic action of CHET on TNBC cells. Cytotoxicity studies were performed in human TNBC cells viz. MDA-MB-231 and MDA-MB-468 cells by Sulforhodamine B assay. It exhibited antiproliferative response and induced apoptosis in both the cell types. Cell cycle analysis revealed that it increases the sub G0/G1 phase cell population. Modulation of mitochondrial membrane potential, activation of caspase 3/7 and a remarkable increase in the expression of cleaved PARP and increased chromatin condensation was observed after CHET treatment in MDA-MB-231 and MDA-MB-468 cells. Additionally, an elevated level of intracellular Ca2+ played an important role in CHET mediated cell death response. Calcium overload in mitochondria led to release of cytochrome c which in turn triggered caspase-3 mediated cell death. Inhibition of calcium signalling using BAPTA-AM reduced apoptosis confirming the involvement of calcium signalling in CHET induced cell death. Chetomin also inhibited PI3K/mTOR cell survival pathway in human TNBC cells. The overall findings suggest that Chetomin inhibited the growth of human TNBC cells by caspase-dependent apoptosis and modulation of PI3K/mTOR signalling and could be used as a novel chemotherapeutic agent for the treatment of human TNBC in future.
📖 Papers frequently viewed together
15 Citations
9 Citations
6 Authors (Luigi Sapio, ..., Silvio Naviglio)
18 Citations
#1Jayant Dewangan (Central Drug Research Institute)H-Index: 9
#2Divya Tandon (Central Drug Research Institute)H-Index: 2
Last. Srikanta Kumar Rath (Central Drug Research Institute)H-Index: 13
view all 6 authors...
Resveratrol (RES) is a natural polyphenol having anti-proliferative activity against breast cancer cells. RES in combination with other chemo modulatory agents, minimizes toxicity and increases efficacy of the treatment. Salinomycin (SAL), a monocarboxylic polyether ionophore is known for selectively targeting breast cancer stem cells. Purpose of the present study was to investigate whether RES in combination with SAL exerts synergistic anti-proliferative activity on breast cancer cells. We furt...
27 CitationsSource
#1Jayant Dewangan (Central Drug Research Institute)H-Index: 9
#2Sonal Srivastava (Central Drug Research Institute)H-Index: 7
Last. Srikanta Kumar Rath (Central Drug Research Institute)H-Index: 20
view all 3 authors...
The primary hurdle in the treatment of cancer is acquisition of resistance by the tumor cells toward multiple drugs and selectively targeting the cancer stem cells. This problem was overcome by the chemotherapeutic property of recently discovered drug salinomycin. Exact mechanism of action of salinomycin is not yet known, but there are multiple pathways by which salinomycin inhibits tumor growth. Salinomycin decreases the expression of adenosine triphosphate–binding cassette transporter in multi...
52 CitationsSource
#1Giampaolo Bianchini (UniSR: Vita-Salute San Raffaele University)H-Index: 26
#2Justin M. Balko (VUMC: Vanderbilt University Medical Center)H-Index: 54
Last. Luca Gianni (UniSR: Vita-Salute San Raffaele University)H-Index: 85
view all 5 authors...
Triple-negative breast cancer has a poor outcome compared with other breast cancer subgroups, and chemotherapy is the primary treatment for this disease. 'Omics' technologies have revealed high levels of heterogeneity and helped to identify potentially actionable molecular features in some triple-negative breast cancer subtypes. Proof-of-principle studies suggest a potential benefit from immunotherapy in patients with this disease. Herein, Bianchini et al. discuss the most promising therapeutic ...
937 CitationsSource
#1Jing Wang (CSU: Central South University)H-Index: 1
#2Yang Xin (CSU: Central South University)H-Index: 1
Last. Zhang Jingjing (CSU: Central South University)H-Index: 1
view all 3 authors...
Abstract Pancreatic β cell dysfunction, i.e., failure to provide insulin in concentrations sufficient to control blood sugar, is central to the etiology of all types of diabetes. Current evidence implicates mitochondrial oxidative stress and endoplasmic reticulum (ER) stress in pancreatic β cell loss and impaired insulin secretion. Oxidative and ER stress are interconnected so that misfolded proteins induce reactive oxygen species (ROS) production; likewise, oxidative stress disturbs the ER redo...
80 CitationsSource
#1Q. Song (Sichuan Agricultural University)H-Index: 3
#2Chunchun Han (Sichuan Agricultural University)H-Index: 13
Last. H. Y. Xu (Sichuan Agricultural University)H-Index: 5
view all 9 authors...
PI3K-Akt-mTOR signaling pathway is associated with endoplasmic reticulum (ER) stress. However, it is not clear how this signaling pathway affects the ER stress. The present study aimed to determine whether the PI3K-Akt-mTOR signaling pathway regulates tunicamycin (TM)-induced increases in mRNA levels of genes involved in the ER stress, to help elucidate the mechanism by which this pathway affects the ER stress in primary goose hepatocytes. Primary hepatocytes were isolated from geese and culture...
10 CitationsSource
#1Joëlle CollignonH-Index: 10
#2Laurence LousbergH-Index: 3
Last. Guy JerusalemH-Index: 50
view all 4 authors...
Triple-negative breast cancers (TNBCs) are defined by the absence of estrogen and progesterone receptors and the absence of HER2 overexpression. These cancers represent a heterogeneous breast cancer subtype with a poor prognosis. Few systemic treatment options exist besides the use of chemotherapy (CT). The heterogeneity of the disease has limited the successful development of targeted therapy in unselected patient populations. Currently, there are no approved targeted therapies for TNBC. Howeve...
141 CitationsSource
#1Elena Viziteu (CNRS: Centre national de la recherche scientifique)H-Index: 3
#2Camille Grandmougin (CNRS: Centre national de la recherche scientifique)H-Index: 2
Last. Jérôme Moreaux (University of Montpellier)H-Index: 33
view all 7 authors...
Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. The constitutive expression of HIF-1α in MM suggests that inhibition of HIF-1α-mediated transcription represents an interesting target in MM. As p300 is a crucial co-activator of hypoxia-inducible transcription, disrupting the complex HIF-1α/p300 to target HIF activity appears to be an attractive strategy. We reported that chetomin, an inhibitor of HIF-1α/p300 interaction, exhibits antitumour activity in human myeloma cell line...
33 CitationsSource
#1Rebecca L. Siegel (ACS: American Cancer Society)H-Index: 67
#2Kimberly D. Miller (ACS: American Cancer Society)H-Index: 28
Last. Ahmedin Jemal (ACS: American Cancer Society)H-Index: 139
view all 3 authors...
Abstract Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute (Surveillance, Epidemiology, and End Results [SEER] Program), the Centers for Disease Control and Prevention (National Program of Cancer Registries), and the North American Association of Central Can...
11.8k CitationsSource
#1Rishabh Kala (UAB: University of Alabama at Birmingham)H-Index: 7
#2Harsh N. Shah (UAB: University of Alabama at Birmingham)H-Index: 1
Last. Trygve O. TollefsbolH-Index: 60
view all 4 authors...
Background Nutrition is believed to be a primary contributor in regulating gene expression by affecting epigenetic pathways such as DNA methylation and histone modification. Resveratrol and pterostilbene are phytoalexins produced by plants as part of their defense system. These two bioactive compounds when used alone have been shown to alter genetic and epigenetic profiles of tumor cells, but the concentrations employed in various studies often far exceed physiologically achievable doses. Triple...
88 CitationsSource
#1Xiyu Zhang (SDU: Shandong University)H-Index: 18
#2Xiyao Wang (SDU: Shandong University)H-Index: 2
Last. Changshun Shao (SDU: Shandong University)H-Index: 51
view all 10 authors...
Isoliensinine, liensinine and neferine are major bisbenzylisoquinoline alkaloids in the seed embryo of lotus (Nelumbo nucifera), and exhibit potential anti-cancer activity. Here, we explored the effects of these alkaloids on triple-negative breast cancer cells and found that among the three alkaloids isoliensinine possesses the most potent cytotoxic effect, primarily by inducing apoptosis. Interestingly, isoliensinine showed a much lower cytotoxicity against MCF-10A, a normal human breast epithe...
84 CitationsSource
Cited By11
#1Sonal SrivastavaH-Index: 7
#2Jayant DewanganH-Index: 9
Last. Srikanta Kumar RathH-Index: 13
view all 8 authors...
Abstract Background: Celecoxib (CXB), a selective COX-2 inhibitor NSAID, has exhibited prominent anti-proliferative potential against numerous cancers. However, its low bioavailability and long term exposure related cardiovascular side effects, limit its clinical application. In order to overcome these limitations, natural bioactive compounds with lower toxicity profile are used in combination with therapeutic drugs. Therfore, in this study Piperine (PIP), a natural chemo-preventive agent posses...
1 CitationsSource
#1Shuiquan Zhang (ECUST: East China University of Science and Technology)
#2Xiaoyu Ma (ECUST: East China University of Science and Technology)H-Index: 8
Last. Changsheng Liu (ECUST: East China University of Science and Technology)H-Index: 65
view all 6 authors...
The rapid development of nanotechnology has provided new strategies for the treatment of tumors. Nano-scale hydroxyapatite (HAP), as the main component of hard tissues in humans and vertebrates, have been found to specifically inhibit tumor cells. However, achieving controllable synthesis of HAP and endowing it with cancer cell-targeting properties remain enormous challenges. To solve this problem, we developed polyacrylic acid-coordinated hydroxyapatite nanoparticles (HAP–PAA) and further chemi...
#1Johanna Salo (Aalto University)H-Index: 3
#2Orsolya Kedves (University of Szeged)H-Index: 4
Last. Heidi Salonen (Aalto University)H-Index: 15
view all 7 authors...
The diversity of Chaetomium-like isolates in buildings in Finland is poorly documented. This paper describes a set of methods for rapid diversity tracking of 42 indoor Chaetomium-like isolates. These isolates were categorized based on their fluorescence emission, ascomatal hair morphology, responses in three bioassays and resistance/sensitivity to the wetting agent Genapol X-080. Thirty-nine toxigenic isolates were identified [Ch. globosum (n = 35), Ch. cochliodes (n = 2) and Ch. rectangulare (n...
2 CitationsSource
#1Shengping Min (Bengbu Medical College)H-Index: 2
#2Xiaoxu Wang (Bengbu Medical College)H-Index: 1
Last. Xiaojing Wang (Bengbu Medical College)H-Index: 11
view all 13 authors...
Non-small cell lung cancer (NSCLC) remains recalcitrant to effective treatment due to tumor relapse and acquired resistance. Cancer stem cells (CSCs) are believed to be one mechanism for relapse an...
1 CitationsSource
#1Chase R. Olsson (MIT: Massachusetts Institute of Technology)H-Index: 2
#2Joshua N. Payette (MIT: Massachusetts Institute of Technology)H-Index: 2
Last. Mohammad Movassaghi (MIT: Massachusetts Institute of Technology)H-Index: 47
view all 4 authors...
We describe our design, synthesis, and chemical study of a set of functional epidithiodiketopiperazines (ETPs) and evaluation of their activity against five human cancer cell lines. Our structure–a...
3 CitationsSource
#1Liyan Zhang (SJTU: Shanghai Jiao Tong University)H-Index: 2
#2Bijun Fan (SJTU: Shanghai Jiao Tong University)H-Index: 2
Last. Xiaoming Tan (SJTU: Shanghai Jiao Tong University)H-Index: 3
view all 8 authors...
Synaptotagmins are a class of proteins that play an important role in the secretion of neurotransmitters by synaptic vesicles. However, recent studies have shown that members of this family also have a certain function in the development of tumors. In this study, we first identified through The Cancer Genome Atlas data analyzed that a novel synaptotagmin, SYT13, was closely related to the prognosis of lung adenocarcinoma, but was not significantly correlated with the prognosis of lung squamous c...
4 CitationsSource
#1Nelson G.M. Gomes (University of Porto)H-Index: 10
#2Renato B. Pereira (University of Porto)H-Index: 6
Last. Patrícia Valentão (University of Porto)H-Index: 73
view all 4 authors...
While several marine natural products bearing the 2,5-diketopiperazine ring have been reported to date, the unique chemistry of dimeric frameworks appears to remain neglected. Frequently reported from marine-derived strains of fungi, many naturally occurring diketopiperazine dimers have been shown to display a wide spectrum of pharmacological properties, particularly within the field of cancer and antimicrobial therapy. While their structures illustrate the unmatched power of marine biosynthetic...
9 CitationsSource
#1Miao He (Guangdong Pharmaceutical University)H-Index: 9
#2Fan Du (Guangdong Pharmaceutical University)H-Index: 10
Last. Yun-Jun Liu (Guangdong Pharmaceutical University)H-Index: 20
view all 9 authors...
Abstract In recent years, ruthenium complexes have attracted extensive attention as new anticancer drugs. In this paper, three new ruthenium complexes [Ru(dmb)2(HMNPIP)](PF6)2 (1), [Ru(bpy)2(HMNPIP)](PF6)2 (2) and [Ru(phen)2(HMNPIP)](PF6)2 (3) (HMNPIP = 2-hydroxy-3-methoxy-5-nitrophenylimidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized by elemental analysis, ESI-MS, 1H NMR and 13C NMR. The MTT assays showed that the complexes have no cytotoxic activity in vitro. However, upon...
7 CitationsSource
#1Jayant Dewangan (Central Drug Research Institute)H-Index: 9
#2Sonal Srivastava (Central Drug Research Institute)H-Index: 7
Last. Srikanta Kumar Rath (Central Drug Research Institute)H-Index: 13
view all 6 authors...
Abstract Cancer is a complex disease wherein cells begin to divide abnormally and spread into surrounding tissues. Angiogenesis plays a crucial role in tumor progression as it is required for sustained growth and metastasis, therefore targeting angiogenesis is a promising therapeutic approach for breast cancer management. Salinomycin (SAL) has been reported to exhibit anticancer response on various types of cancer. In the present study, we explored the antiangiogenic and anticancer efficacy of t...
18 CitationsSource
#1Sonal Srivastava (Central Drug Research Institute)H-Index: 7
#2Sakshi Mishra (Central Drug Research Institute)H-Index: 11
Last. Srikanta Kumar Rath (Central Drug Research Institute)H-Index: 13
view all 10 authors...
Background Diethylene glycol monoethyl ether (DEGEE) is widely used as a solubilizer in cosmetics as well as in oral, topical, transdermal and injectable pharmaceutical formulations. Due to the unavailability of detailed toxicological studies on DEGEE, the Scientific Committee on Consumer Products (SCCP) found its toxicological reports to be unsatisfactory, comprising only summaries. Also, a few reports have raised concern on the use of DEGEE as it might cause damage to the kidneys.
4 CitationsSource