A Novel Dialkylamino-Functionalized Chalcone, DML6, Inhibits Cervical Cancer Cell Proliferation, In Vitro, via Induction of Oxidative Stress, Intrinsic Apoptosis and Mitotic Catastrophe

Len, Jenna M.; Hussein, Noor; Malla, Saloni; McIntosh, Kyle; Patidar, Rahul; Manivannan, Elangovan; Karthikeyan, Chandrabose; Moorthy, N. S. Hari Narayana; Pandey, Manoj K.; Raman, Dayanidhi; Trivedi, Piyush; Tiwari, Amit K.

doi:10.3390/molecules26144214

Cited by 8 publications

(4 citation statements)

References 66 publications

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“…[ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Furthermore, induction of both intrinsic and extrinsic apoptosis pathways associated with caspases activation, modulation of the Bcl-2 family protein activity, impairment of mitochondrial function with subsequent release of proapoptotic factors such as cytochrome c has also been experimentally proven [ 27 , 28 ]. Some of the above-mentioned effects have also been demonstrated by experiments from our laboratory [ 14 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Programmed Cell Death Alterations Mediated by Synthetic Indole Chalcone Resulted in Cell Cycle Arrest, DNA Damage, Apoptosis and Signaling Pathway Modulations in Breast Cancer Model

et al. 2022

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Although new chemotherapy significantly increased the survival of breast cancer (BC) patients, the use of these drugs is often associated with serious toxicity. The discovery of novel anticancer agents for BC therapy is expected. This study was conducted to explore the antiproliferative effect of newly synthesized indole chalcone derivative ZK-CH-11d on human BC cell lines. MTT screening, flow cytometry, Western blot, and fluorescence microscopy were used to evaluate the mode of cell death. ZK-CH-11d significantly suppressed the proliferation of BC cells with minimal effect against non-cancer cells. This effect was associated with cell cycle arrest at the G2/M phase and apoptosis induction. Apoptosis was associated with cytochrome c release, increased activity of caspase 3 and caspase 7, PARP cleavage, reduced mitochondrial membrane potential, and activation of the DNA damage response system. Furthermore, our study demonstrated that ZK-CH-11d increased the AMPK phosphorylation with simultaneous inhibition of the PI3K/Akt/mTOR pathway indicating autophagy initiation. However, chloroquine, an autophagy inhibitor, significantly potentiated the cytotoxic effect of ZK-CH-11d in MDA-MB-231 cells indicating that autophagy is not principally involved in the antiproliferative effect of ZK-CH-11d. Taking together the results from our experiments, we assume that autophagy was activated as a defense mechanism in treated cells trying to escape from chalcone-induced harmful effects.

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Section: Introductionmentioning

confidence: 99%

Programmed Cell Death Alterations Mediated by Synthetic Indole Chalcone Resulted in Cell Cycle Arrest, DNA Damage, Apoptosis and Signaling Pathway Modulations in Breast Cancer Model

et al. 2022

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“…Chalcones have been demonstrated to inhibit tumor progression and development in cancers [12][13][14][15][16][17][18], including glioma [15,18]. The synthetic Chalcone 9X is an aromatic ketone, which has been proved to own antitumor activities in lung cancer cells and hepatic cancer cells through activating Caspase-3 and Caspase-8 signaling pathway [19].…”

Section: Discussionmentioning

confidence: 99%

“…Natural and chemical synthetic chalcones have been revealed to play critical roles in some biological functions, such as inflammation [7][8][9] and antibacterial effects [10,11]. Furthermore, more studies demonstrated that chalcones could inhibit tumor progression in various cancers [12][13][14][15][16][17][18][19], including glioma [15,18]. For example, Mendanha et al found that Chalcone 1 could induce cell apoptosis of glioblastoma (GBM), which was triggered by the cell cycle arrest in the G2/M checkpoint, and might be a potential to provide a new treatment alternative for GBM 15 .…”

Section: Introductionmentioning

confidence: 99%

Chalcone 9X Contributed to Repressing Glioma Cell Growth and Migration and Inducing Cell Apoptosis by Reducing FOXM1 Expression In Vitro and Repressing Tumor Growth In Vivo

Li¹,

Wang²,

Guo³

et al. 2022

BioMed Research International

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Objective. Natural and synthetic chalcones played roles in inflammation and cancers. Chalcone 9X was an aromatic ketone that was found to inhibit cell growth of hepatic cancer and lung cancer cells. In this study, we wanted to investigate the functions of Chalcone 9X in glioma. Materials and Methods. Chemical Chalcone 9X was added in human glioma cell lines (U87 and T98G cells) and normal astrocyte cell lines (HA1800) with various concentrations (0 μmol/L, 20 μmol/L, 50 μmol/L, and 100 μmol/L). CCK-8 assay was used to measure cell viability. Flow cytometric assay was used to measure cell apoptotic rates. Wound healing assay and transwell assay were used to measure cell invasion. RT-PCR was used to detect relative mRNA expressions, and the protein expressions were detected by western blot (WB) and immunohistochemical staining (IHC). Finally, nude mouse xenograft assay was performed to prove the effects of Chalcone 9X in vivo. Results. Results revealed that Chalcone 9X treatment suppressed cell viability and cell migration capacity; it could also induce cell apoptosis in U87 and T98G cells with dose dependence. However, it had little cytotoxicity to normal astrocyte HA1800 cells. Moreover, Chalcone 9X treatment could repress the mRNA and protein expressions of FOXM1 in human glioma cell lines, which was an oncogene that could promote the progression and malignancy of glioma. In addition, FOXM1 overexpression dismissed the Chalcone 9X effects on cell proliferation, apoptosis, and migration in human glioma cell lines. Finally, in vivo assay showed that Chalcone 9X treatment repressed the expression of FOXM1, which inhibited the tumor growth of a xenograft model injected with U87 in nude mice. Conclusions. In all, we found that Chalcone 9X could suppress cell proliferation and migration and induce cell apoptosis in human glioma cells, while it has little cytotoxicity to normal astrocyte cells. Therefore, we uncovered a novel way that Chalcone 9X could inhibit FOXM1 expression and repress the progression and biofunctions of glioma cells, which might be a potential therapeutic drug for treating human glioma.

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“…Chalcones also present a wide activity against different diseases, which became a good fragment for the diversity of biological activities and an important synthetic intermediate. [15][16][17] Among the biological activities, chalcone derivatives have been reported as antiproliferative agents due to their ability to induce apoptosis, [20][21][22][23] and mitotic catastrophe by increasing proapoptotic proteins, as well as increasing the levels of reactive oxygen species that collapse the mitochondrial membrane potential, [20] repress cell proliferation and migration capacities through activating caspases (3,7,8, or 9) signaling pathway, [21] and affect cell cycle changes, [22,23] inhibiting the growth of different cancer cell such as cervical cancer, [20] breast cancer, [22] hepatic cancer and lung cancer. [21] Furthermore, chalcones have been also evaluated as potential antifungal, [24] antibacterial, [25] and antiviral [26] agents.…”

mentioning

confidence: 99%

New pyridine‐based chalcones and pyrazolines with anticancer, antibacterial, and antiplasmodial activities

Ramírez‐Prada,

Rocha‐Ortiz,

Orozco

et al. 2024

Archiv der Pharmazie

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New pyridine‐based chalcones 4a–h and pyrazolines 5a–h (N‐acetyl), 6a–h (N‐phenyl), and 7a–h (N‐4‐chlorophenyl) were synthesized and evaluated by the National Cancer Institute (NCI) against 60 different human cancer cell lines. Pyrazolines 6a, 6c–h, and 7a–h satisfied the pre‐determined threshold inhibition criteria, obtaining that compounds 6c and 6f exhibited high antiproliferative activity, reaching submicromolar GI50 values from 0.38 to 0.45 μM, respectively. Moreover, compound 7g (4‐CH3) exhibited the highest cytostatic activity of these series against different cancer cell lines from leukemia, nonsmall cell lung, colon, ovarian, renal, and prostate cancer, with LC50 values ranging from 5.41 to 8.35 μM, showing better cytotoxic activity than doxorubicin. Furthermore, the compounds were tested for antibacterial and antiplasmodial activities. Chalcone 4c was the most active with minimal inhibitory concentration (MIC) = 2 μg/mL against methicillin‐resistant Staphylococcus aureus (MRSA), while the pyrazoline 6h showed a MIC = 8 μg/mL against Neisseria gonorrhoeae. For anti‐Plasmodium falciparum activity, the chalcones display higher activity with EC50 values ranging from 10.26 to 10.94 μg/mL. Docking studies were conducted against relevant proteins from P. falciparum, exhibiting the minimum binding energy with plasmepsin II. In vivo toxicity assay in Galleria mellonella suggests that most compounds are low or nontoxic.

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A Novel Dialkylamino-Functionalized Chalcone, DML6, Inhibits Cervical Cancer Cell Proliferation, In Vitro, via Induction of Oxidative Stress, Intrinsic Apoptosis and Mitotic Catastrophe

Cited by 8 publications

References 66 publications

Programmed Cell Death Alterations Mediated by Synthetic Indole Chalcone Resulted in Cell Cycle Arrest, DNA Damage, Apoptosis and Signaling Pathway Modulations in Breast Cancer Model

Programmed Cell Death Alterations Mediated by Synthetic Indole Chalcone Resulted in Cell Cycle Arrest, DNA Damage, Apoptosis and Signaling Pathway Modulations in Breast Cancer Model

Chalcone 9X Contributed to Repressing Glioma Cell Growth and Migration and Inducing Cell Apoptosis by Reducing FOXM1 Expression In Vitro and Repressing Tumor Growth In Vivo

New pyridine‐based chalcones and pyrazolines with anticancer, antibacterial, and antiplasmodial activities

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