A novel quinazolinone chalcone derivative induces mitochondrial dependent apoptosis and inhibits PI3K/Akt/mTOR signaling pathway in human colon cancer HCT-116 cells

Wani, Zahoor A.; Guru, Santosh Kumar; Rao, A. V. Subba; Sharma, Shrestha; Mahajan, Girish; Behl, Akanksha; Kumar, Ashok; Sharma, Parduman R.; Kamal, Ähmed; Bhushan, Shashi; Mondhe, Dilip M.

doi:10.1016/j.fct.2015.11.016

Cited by 64 publications

(37 citation statements)

References 22 publications

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“…Rapamycin, an mTOR inhibitor, induces apoptosis of human osteosarcoma Mg63 cells (30). Quinazolinone chalcone derivative inhibits the PI3K/Akt/mTOR signaling pathway and induces mitochondrial-dependent apoptosis in human colorectal adenocarcinoma HCT-116 cells (31). We revealed for the first time that NVP-BEZ235, a dual inhibitor of PI3K and mTOR, inhibited proliferation and induced apoptosis of HT-29 human colorectal adenocarcinoma cells.…”

Section: Discussionmentioning

confidence: 83%

Effects of NVP-BEZ235 on the proliferation, migration, apoptosis and autophagy in HT-29 human colorectal adenocarcinoma cells

et al. 2016

International Journal of Oncology

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The phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) pathway plays a significant role in colorectal adenocarcinoma. NVP-BEZ235 (dactolisib) is a novel dual inhibitor of PI3K/mTOR. The effects of NVP-BEZ235 in human colorectal adenocarcinoma are still unclear. In the present study, we aimed to explore the proliferation, migration, apoptosis and autophagy in HT-29 human colorectal adenocarcinoma cells. HT-29 human colorectal adenocarcinoma cells were treated with NVP-BEZ235 (0, 0.001, 0.01, 0.1, 1 and 3 µM) for 24 and 48 h, respectively. Cells were also treated with NVP-BEZ235 (0.1 µM), DDP (100, 300 and 1,000 µM), and NVP-BEZ235 (0.1 µM) combined with DDP (100, 300 and 1,000 µM) respectively, and cultured for 24 h after treatment. MTT assay was utilized to evaluate the effects of NVP-BEZ235 alone or NVP-BEZ235 combined with cis-diamminedichloroplatinum (DDP) on proliferation of HT-29 cells. Cell wound-scratch assay was used detect cell migration. In addition, expression of microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B and LC3B) in HT-29 cells was detected by immunofluorescence at 48 h after NVP-BEZ235 (1 µM) treatment. Expression of proteins involved in cell cycle and proliferation (p-Akt, p-mTOR and cyclin D1), apoptosis (cleaved caspase-3), and autophagy (cleaved LC3B and Beclin-1) were detected by western blot analysis. NVP-BEZ235 inhibited the proliferation and migration of HT-29 human colorectal adenocarcinoma cells. NVP-BEZ235 decreased protein expression of p-Akt, p-mTOR and cyclin D1, and increased protein expression of cleaved caspase-3, cleaved LC3B and Beclin-1 as the concentrations and the incubation time of NVP-BEZ235 increased. In addition, NVP-BEZ235 and DDP had synergic effects in inhibiting cell proliferation and migration. The expression of protein involved in apoptosis (cleaved caspase-3) was higher in drug combination group compared to the NVP-BEZ235 single treatment group. NVP-BEZ235 inhibited the proliferation and migration, and induced apoptosis and autophagy of HT-29 human colorectal adenocarcinoma cells.

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Section: Discussionmentioning

confidence: 83%

Effects of NVP-BEZ235 on the proliferation, migration, apoptosis and autophagy in HT-29 human colorectal adenocarcinoma cells

et al. 2016

International Journal of Oncology

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“…Mitochondrial damage to cells results in perturbation of the mitochondrial membrane potential (ΔΨm) [15]. We evaluated changes in the ΔΨm in NOZ and SGC996 cells using Rhodamine 123 staining, as the decrease in the intensity of Rhodamine 123 staining reflects mitochondrial membrane potential and integrity.…”

Section: Resultsmentioning

confidence: 99%

Casticin induces apoptosis and G0/G1 cell cycle arrest in gallbladder cancer cells

et al. 2017

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BackgroundCasticin, the flavonoid extracted from Vitex rotundifolia L, exerts various biological effects, including anti-inflammatory and anti-cancer activity. The aim of this study is to investigate the effects and mechanisms of casticin in human gallbladder cancer cells.MethodsHuman NOZ and SGC996 cells were used to perform the experiments. CCK-8 assay and colony formation assay were performed to evaluate cell viability. Cell cycle analyses and annexin V/PI staining assay for apoptosis were measured using flow cytometry. Western blot analysis was used to evaluate the changes in protein expression, and the effect of casticin treatment in vivo was experimented with xenografted tumors.ResultsIn this study, we found that casticin significantly inhibited gallbladder cancer cell proliferation in a dose- and time-dependent manner. Casticin also induced G0/G1 arrest and mitochondrial-related apoptosis by upregulating Bax, cleaved caspase-3, cleaved caspase-9 and cleaved poly ADP-ribose polymerase expression, and by downregulating Bcl-2 expression. Moreover, casticin induced cycle arrest and apoptosis by upregulating p27 and downregulating cyclinD1/cyclin-dependent kinase4 and phosphorylated protein kinase B. In vivo, casticin inhibited tumor growth.ConclusionCasticin induces G0/G1 arrest and apoptosis in gallbladder cancer, suggesting that casticin might represent a novel and effective agent against gallbladder cancer.

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“…In recent years, attention has been focused on the anti-cancer properties of natural products, which play an important role in the prevention of cancers 2 . As an important candidates of the subclasses of the flavonoid family, chalcone derivatives are the precursors of the flavones in the biosynthesis of flavonoids and a large amount of which have been applied as antiplatelet, anti-inflammatory, anti-allergic, antimicrobial, antioxidant or anti-tumor agent 3 , 4 . The most classical and general synthetic route of chalcone derivatives was the Claisen-Schmidt condensation among the reported ones 5 .…”

Section: Introductionmentioning

confidence: 99%

A novel chalcone derivative S17 induces apoptosis through ROS dependent DR5 up-regulation in gastric cancer cells

Zhang

et al. 2017

Sci Rep

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A new series of etherification chalcone derivatives were designed and synthesized through Willimison etherification and Claisen-Schmidt condensation. Among them, compound 2-c which was given chemical name of S17, has been successfully screened out as the most potent one on gastric cancer cell line(MGC803) through the investigation for their effects against the growth of five cancer cell lines (EC109, HepG2, MCF7, MGC803, SKNSH). S17 exhibited strong anti-proliferative activity on other two gastric cancer cells (HGC27 and SGC7901), but less cytotoxicity to non-malignant gastric epithelial cells GES1. S17 potently killed gastric cancer cells with causing modulation of Bcl-2 family proteins and activation of caspase 9/3 cascade. S17 also up-regulated DR5 expression and DR5 knockdown partially reversed S17-induced apoptosis, caspase activation and MMP decrease. S17 robustly induced generation of ROS with Keap/Nrf2 pathway activated and the application of ROS scavenger N-acetyl cysteine (NAC) completely blocked these effects by S17 in MGC803 cells. Intraperitoneal administration of S17 significantly inhibited the growth of MGC803 cells in vivo in a xenograft mouse model without observed toxicity. These results indicated that S17 is a leadbrominated chalcone derivate and deserves further investigation for prevention and treatment of gastric cancer.

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A novel quinazolinone chalcone derivative induces mitochondrial dependent apoptosis and inhibits PI3K/Akt/mTOR signaling pathway in human colon cancer HCT-116 cells

Cited by 64 publications

References 22 publications

Effects of NVP-BEZ235 on the proliferation, migration, apoptosis and autophagy in HT-29 human colorectal adenocarcinoma cells

Effects of NVP-BEZ235 on the proliferation, migration, apoptosis and autophagy in HT-29 human colorectal adenocarcinoma cells

Casticin induces apoptosis and G0/G1 cell cycle arrest in gallbladder cancer cells

A novel chalcone derivative S17 induces apoptosis through ROS dependent DR5 up-regulation in gastric cancer cells

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