Novel vitamin D3 analog, 21-(3-methyl-3-hydroxy-butyl)-19-nor D3, that modulates cell growth, differentiation, apoptosis, cell cycle, and induction of PTEN in leukemic cells

Blood ◽  
2001 ◽  
Vol 97 (8) ◽  
pp. 2427-2433 ◽  
Author(s):  
Jun-ichi Hisatake ◽  
James O'Kelly ◽  
Milan R. Uskokovic ◽  
Shigeru Tomoyasu ◽  
H. Phillip Koeffler
Keyword(s):  
Cancer Cells ◽  
Vitamin D3 ◽  
Active Form ◽  
Annexin V ◽  
Pten Expression ◽  
Leukemic Cells ◽  
Side Chains ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Mcf 7

Abstract The active form of vitamin D3, 1,25(OH)2D3, inhibits proliferation and induces differentiation of a variety of malignant cells. A new class of vitamin D3 analogs, having 2 identical side chains attached to carbon-20, was synthesized and the anticancer effects evaluated. Four analogs were evaluated for their ability to inhibit growth of myeloid leukemia (NB4, HL-60), breast (MCF-7), and prostate (LNCaP) cancer cells. All 4 analogs inhibited growth in a dose-dependent manner. Most effective was 21-(3-methyl-3-hydroxy-butyl)-19-nor D3(Gemini-19-nor), which has 2 side chains and removal of the C-19. Gemini-19-nor was approximately 40 625-, 70-, 23-, and 380-fold more potent than 1,25(OH)2D3 in inhibiting 50% clonal growth (ED50) of NB4, HL-60, MCF-7, and LNCaP cells, respectively. Gemini-19-nor (10−8 M) strongly induced expression of CD11b and CD14 on HL-60 cells (90%); in contrast, 1,25(OH)2D3 (10−8 M) stimulated only 50% expression. Annexin V assay showed that Gemini-19-nor and 1,25(OH)2D3 induced apoptosis in a dose-dependent fashion. Gemini-19-nor (10−8 M, 4 days) caused apoptosis in approximately 20% of cells, whereas 1,25(OH)2D3 at the same concentration did not induce apoptosis. Gemini-19-nor increased in HL-60 both the proportion of cells in the G1/G0 phase and expression level of p27kip1. Moreover, Gemini-19-nor stimulated expression of the potential tumor suppressor, PTEN. Furthermore, other inducers of differentiation, all-trans-retinoic acid and 12-O-tetradecanoylphorbol 13-acetate, increased PTEN expression in HL-60. In summary, Gemini-19-nor strongly inhibited clonal proliferation in various types of cancer cells, especially NB4 cells, suggesting that further studies to explore its anticancer potential are warranted. In addition, PTEN expression appears to parallel terminal differentiation of myeloid cells.

scholarly journals Anticancer Potential of Fruit Extracts from Vatica diospyroides Symington Type SS and Their Effect on Program Cell Death of Cervical Cancer Cell Lines

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Atchara Chothiphirat ◽  
Kesara Nittayaboon ◽  
Kanyanatt Kanokwiroon ◽  
Theera Srisawat ◽  
Raphatphorn Navakanitworakul
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Morphological Changes ◽  
Annexin V ◽  
Siha Cell ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Cervical Cancer Cells ◽  
Dose Dependent

Vatica diospyroides Symington is locally known as Chan-Ka-Pho in Thailand. Ancient people have used it as therapeutic plant for cardiac and blood tonic cure. The purpose of this study was to investigate the potential cytotoxicity and selectivity of the extracts from V. diospyroides type SS fruit on cervical cancer HeLa and SiHa cell lines and to examine its underlying mechanism of action. MTT assay revealed that the extracts showed inhibition of cell survival in a dose-dependent manner and exhibited highly cytotoxic activity against both HeLa and SiHa cells with IC50 value less than 20 μg/mL along with less toxicity against L929 cells. Acetone cotyledon extract (ACE) showed the best selectivity index value of 4.47 (HeLa) and 3.51 (SiHa). Distinctive morphological changes were observed in ACE-treated cervical cancer cells contributing to apoptosis action. Flow cytometry analysis with Annexin V-FITC and PI staining precisely indicated that ACE induced apoptosis in HeLa and SiHa cell lines in a dose-dependent manner. Treatment of ACE with half IC50 caused DNA fragmentation and also activated increasing of bax and cleaved caspase-8 protein in HeLa cells after 48 h exposure. The results suggest that ACE has potent and selective cytotoxic effect against cervical cancer cells and the potential to induce bax and caspase-8-dependent apoptosis. Hence, the ACE could be further exploited as a potential lead in cancer treatment.

scholarly journals Extract of Rhus verniciflua Stokes Induces p53-Mediated Apoptosis in MCF-7 Breast Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Min Sung Kim ◽  
Chul Won Lee ◽  
Jung-Hoon Kim ◽  
Jang-Cheon Lee ◽  
Won Gun An
Keyword(s):  
Breast Cancer ◽  
High Performance ◽  
Annexin V ◽  
Food Supplement ◽  
Dependent Manner ◽  
Related Factors ◽  
Rhus Verniciflua Stokes ◽  
Rhus Verniciflua ◽  
Dose Dependent ◽  
Mcf 7

Rhus verniciflua Stokes has long been used as a food supplement and traditional herbal medicine for various ailments in East Asia. We evaluated the anticancer effects of Rhus verniciflua Stokes extract (RVSE) on MCF-7 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, annexin V/7-AAD staining, and western blotting. In addition, the gallic acid content of RVSE was assayed using high-performance liquid chromatography. RVSE inhibited the growth of MCF-7 cells in a dose-dependent manner by inducing apoptosis in the sub-G1 phase. RVSE also significantly increased the number of apoptotic cells and increased the expression of p53 and p21 in a dose-dependent manner. Furthermore, RVSE treatment increased the Bax:Bcl-2 ratio and the levels of apoptosis-related factors, such as cleaved caspase-3 and -9 and PARP, in MCF-7 cells. Our findings suggest that the proapoptotic effect of RVSE on MCF-7 cells is mediated by p53, p21, and the intrinsic mitochondrial cascade. Thus, RVSE shows promise for the prevention and treatment of breast cancer.

scholarly journals Bersavine: A Novel Bisbenzylisoquinoline Alkaloid with Cytotoxic, Antiproliferative and Apoptosis-Inducing Effects on Human Leukemic Cells

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 964 ◽  
Author(s):  
Darja Koutova ◽  
Monika Kulhava ◽  
Radim Havelek ◽  
Martina Majorosova ◽  
Karel Královec ◽  
...  
Keyword(s):  
Leukemic Cells ◽  
Dependent Manner ◽  
Carcinoma Cell Lines ◽  
Ic50 Values ◽  
Bisbenzylisoquinoline Alkaloid ◽  
Human Leukemic Cells ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
Increased Activity ◽  
Mcf 7

Bersavine is the new bisbenzylisoquinoline alkaloid isolated from the Berberis vulgaris L. (Berberidaceae) plant. The results of cytotoxicity screening 48 h post-treatment showed that bersavine considerably inhibits the proliferation and viability of leukemic (Jurkat, MOLT-4), colon (HT-29), cervix (HeLa) and breast (MCF-7) cancer cells with IC50 values ranging from 8.1 to 11 µM. The viability and proliferation of leukemic Jurkat and MOLT-4 cells were decreased after bersavine treatment in a time- and dose-dependent manner. Bersavine manifested concentration-dependent antiproliferative activity in human lung, breast, ovarian and hepatocellular carcinoma cell lines using a xCELLigence assay. Significantly higher percentages of MOLT-4 cells exposed to bersavine at 20 µM for 24 h were arrested in the G1 phase of the cell cycle using the flow cytometry method. The higher percentage of apoptotic cells was measured after 24 h of bersavine treatment. The upregulation of p53 phosphorylated on Ser392 was detected during the progression of MOLT-4 cell apoptosis. Mechanistically, bersavine-induced apoptosis is an effect of increased activity of caspases, while reduced proliferation seems dependent on increased Chk1 Ser345 phosphorylation and decreased Rb Ser807/811 phosphorylation in human leukemic cells.

scholarly journals Screening Antitumor Compounds Psoralen and Isopsoralen fromPsoralea corylifoliaL. Seeds

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Yi Wang ◽  
Chengtao Hong ◽  
Chenguang Zhou ◽  
Dongmei Xu ◽  
Hai-bin Qu
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Annexin V ◽  
Volatile Fraction ◽  
Dependent Manner ◽  
Psoralea Corylifolia ◽  
Medical Plant ◽  
Apoptotic Activity ◽  
Fraction I ◽  
Dose Dependent

Psoralea corylifoliaL. (Fabaceae) is a widely used medical plant in China. This study was designed to screen and identify bioactive compounds with anticancer activity from the seeds ofPsoralea corylifoliaL. One volatile fraction (fraction I) and three other fractions (fraction II, III, IV) from methanol extraction ofP. corylifoliaL. were obtained. Bioactivities of these fractions were evaluated by the cytotoxicity on KB, KBv200, K562, K562/ADM cancer cells with MTT assay. Major components in the active fraction were identified by HPLC/MSn. Fraction IV significantly inhibits the growth of cancer cells in a dose-dependent manner. The IC50values were 21.6, 24.4, 10.0 and 26.9, respectively. Psoralen and isopsoralen, isolated from fraction IV, were subject to bioactive assay and presented a dose-dependent anticancer activity in four cancer cell lines (KB, KBv200, K562 and K562/ADM). The IC50values of psoralen were 88.1, 86.6, 24.4 and 62.6, which of isopsoralen were 61.9, 49.4, 49.6 and 72.0, respectively. Apoptosis of tumor cell significantly increased after treated with psoralen and isopsoralen. Induction of apoptotic activity was confirmed by flow cytometry after staining with Annexin V/PI. These results suggested psoralen and isopsoralen contribute to anticancer effect ofP. corylifoliaL.

scholarly journals Effect of Sterols Isolated fromMyrtillocactus geometrizanson Growth Inhibition of Colon and Breast Cancer Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Mario Augusto Bolaños-Carrillo ◽  
Jose Luis Ventura-Gallegos ◽  
Arturo David Saldivar-Jiménez ◽  
Alejandro Zentella-Dehesa ◽  
Mariano Martínez-Vázquez
Keyword(s):  
Cell Cycle ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Biological Activities ◽  
Annexin V ◽  
Parp Cleavage ◽  
Dependent Manner ◽  
Cycle Dependent ◽  
Mcf 7

Objective. To explore the effect of peniocerol and macdougallin on HCT-15 and MCF-7 cells proliferation, cell cycle, apoptosis, and PARP cleavage.Methods. HCT-15 and MCF-7 cells were treated with various concentrations of peniocerol and macdougallin (10–80 μM) during 24 or 48 h. Crystal Violet Assay was used to evaluate the inhibition effect. Cell cycle regulation was examined by a propidium iodide method. Cell apoptosis was detected through both Annexin–V FLUOS/PI double-labeled cytometry assays and Western blot was applied to assess PARP cleavage.Results. Peniocerol and macdougallin induced growth inhibition and apoptosisin vitroin a time- and dose-dependent manner. Moreover, peniocerol and macdougallin induced arrest of cell cycle-dependent manner and increased the proportion of cells in G0/G1phase. PARP cleavage in HCT-15 and MCF-7 cells was induced by treatment with peniocerol and macdougallin after 36 hours.Conclusions. Our results showed that the mechanism of cytotoxicity displayed by peniocerol and macdougallin is related to cell cycle arrest and apoptosis in both cell lines. This is a significant observation because it helps to understand the way some oxysterols isolated fromMyrtillocactus geometrizansdevelop their biological activities against cancer cells.

scholarly journals Identification and Characterization of the Caspase-Mediated Apoptotic Activity of Teucrium mascatense and an Isolated Compound in Human Cancer Cells

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 977 ◽  
Author(s):  
Neena Panicker ◽  
Sameera Balhamar ◽  
Shaima Akhlaq ◽  
Mohammed Qureshi ◽  
Tania Rizvi ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Annexin V ◽  
Dependent Manner ◽  
Human Cancer Cells ◽  
Cell Death Pathways ◽  
Proliferative Effect ◽  
Mcf 7

Plants of the genus Teucrium (Lamiaceae or Labiatae family) are known historically for their medicinal value. Here, we identify and characterize the anticancer potential of T. mascatense and its active compound, IM60, in human cancer cells. The anti-proliferative effect of a T. mascatense methanol extract and its various fractions were analyzed in MCF-7 and HeLa cells in a dose- and time dependent manner. The dichloromethane fraction (TMDF) was observed to be the most effective with cytotoxicity against a more expanded series of cell lines, including MDA-MB-231. A time and dose-dependent toxicity profile was also observed for IM60; it could induce rapid cell death (within 3 h) in MCF-7 cells. Activation of caspases and PARP, hallmarks of apoptotic cell death pathways, following treatment with TMDF was demonstrated using western blot analysis. Inversion of the phosphatidylserine phospholipid from the inner to the outer membrane was confirmed by annexin V staining that was inhibited by the classical apoptosis inhibitor, Z-VAK-FMK. Changes in cell rounding, shrinkage, and detachment from other cells following treatment with TMDF and IM60 also supported these findings. Finally, the potential of TMDF and IM60 to induce enzymatic activity of caspases was also demonstrated in MCF-7 cells. This study, thus, not only characterizes the anticancer potential of T. mascatense, but also identifies a lead terpenoid, IM60, with the potential to activate anticancer cell death pathways in human cancer cells.

Novel Deuterated Gemini-Vitamin D3 Analogs Have Potent Antitumor Activity.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4210-4210
Author(s):  
Ryoko Okamoto ◽  
Tsuyako Saito ◽  
Talin Haritunians ◽  
James O’Kelly ◽  
Milan Uskokovic ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Vitamin D3 ◽  
Active Form ◽  
Surface Proteins ◽  
Dependent Manner ◽  
Differentiation Markers ◽  
Clonal Proliferation ◽  
Cycle Arrest ◽  
Preclinical And Clinical Studies ◽  
Mcf 7

Abstract The active form of vitamin D3, 1,25(OH)2D3, is an important regulator of calcium and bone metabolism. Also, it inhibits proliferation and induces differentiation of a variety of malignant cells. Here, we synthesized a new class of vitamin D3 analogs, which have a C-20 methyl group and a deuterium substituted basic side chain [Deuterated Gemini (DG)]. Six DG analogs were evaluated for their ability to inhibit growth of myeloid leukemia (HL-60), prostate (LNCaP and PC-3), lung (H520) and breast (MCF-7) cancer cell lines. All 6 DG analogs inhibited growth in a dose-dependent manner and had very similar potency. Most effective DG, BXL-01-0120, was over 70-fold more potent than 1,25(OH)2D3 in inhibiting 50% clonal growth (ED50) of HL-60, LNCaP, PC-3, H520 and MCF-7 cells with ED50s ranging from 10−11 M to 10−13 M. Focusing on this analog for further analyses, pulse-exposure, wash and culture experiments showed that 48 hours exposure of HL-60 cells to BXL-01-0120 (10−9 M) had potent anti-proliferative activity (82% growth inhibition compared to diluent control cells). Cell cycle assays found that BXL-01-0120 (10−10 M, 4 days) increased the percent of cells in the G0/G1-phase (61%, diluent control 47%) associated with a decrease S-phase (18%, diluent control 42%). BXL-01-0120 (10−10 M, 4 days) caused apoptosis in approximately 15% of cells. 1,25(OH)2D3 at the same concentration and duration changed neither the cell cycle nor number of cells undergoing apoptosis compared to control HL-60 cells. BXL-01-0120 (10−10 M, 4 days) strongly induced expression of the CD11b and CD14 (monocyte / macrophage differentiation markers) on HL-60 cells (87%); in contrast, 1,25(OH)2D3(10−10 M) stimulated a mean 43% of the cells to express these cell surface proteins. In summary, DGs strongly inhibited clonal proliferation, induced differentiation and cell cycle arrest in several types of cancer cells, especially HL-60 cells, suggesting that further preclinical and clinical studies to explore their anticancer potential are warranted.

Anticancer Activities of Phlogacanthus pulcherrimus T. Anderson Leaves Extract on MCF-7 Breast Cancer Cells

2021 ◽  
Vol 901 ◽  
pp. 16-21
Author(s):  
Supavadee Boontha ◽  
Benjaporn Buranrat ◽  
Prapapan Temkitthawon ◽  
Tasana Pitaksuteepong
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Leaf Extract ◽  
Dependent Manner ◽  
Ros Formation ◽  
Dose Dependent ◽  
Ethanolic Leaf Extract ◽  
Mcf 7

Phlogacanthus pulcherrimus T. Anderson (PPT) is an edible plant found in the northern and northeastern regions of Thailand. There is limited information about the anti-breast cancer activity of the ethanolic leaf extract of PPT. This study aimed to evaluate the effects of an ethanolic leaf extract of PPT on MCF-7 breast cancer cell lines. The biological effects, including cytotoxicity, cell apoptosis, colony formation, reactive oxygen species (ROS) formation and cell migration, were determined by a means of sulforhodamine B (SRB), acridine orange/ethidium bromide (AO/EB) staining, a clonogenic assay, flow cytometry and a scratch wound healing assay, respectively. The results demonstrated that the PPT extract showed cytotoxic on MCF-7 cells in a dose-dependent manner with 50% inhibitory concentration (IC50) values of 119.9 ± 12.1 and 51.3 ± 4.7 μg/mL at 24 h and 48 h incubation, respectively. In addition, the extract exhibited cell apoptosis in a dose-dependent manner when used at a concentration of 50–100 μg/mL and inhibited colony formation with an IC50 value of 26.0 ± 2.0 μg/mL when compared with the control group. The extract induced ROS formation in a dose-dependent manner when used at a concentration of 50–100 μg/mL. The extract suppressed MCF-7 cell migration, with significant effect at 25 μg/mL. These results indicate that PPT ethanolic leaf extract has an anticancer activity against MCF-7 breast cancer cells and may be useful for prevention and treatment of breast cancer.

scholarly journals Cytotoxic and apoptosis inducing effect of some pyrano [3, 2-c] pyridine derivatives against MCF-7 Breast Cancer Cells

2018 ◽  
Vol 65 (3) ◽  
Author(s):  
Mohammad Rahnamay ◽  
Majid Mahdavi ◽  
Ali Akbar Shekarchi ◽  
Payman Zare ◽  
Mohammad Ali Hosseinpour Feizi
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Time Course ◽  
Annexin V ◽  
Cell Cycle Analysis ◽  
Outer Cell ◽  
Dependent Manner ◽  
Mcf 7

Anti-cancer activities of some pyrano-pyridines have been previously reported. Herein, we investigated anti-proliferative and apoptotic effects of the novel pyrano [3, 2-c] pyridine (P.P, TPM.P, 4-CP.P and 3-NP.P) compounds against MCF-7 breast cancer cells. The MCF-7 cells were cultured in the presence of various concentrations (20-200 μM) of the compounds for 3 days and the cell viability was determined by MTT assay. Induction of apoptosis was qualitatively assayed by acridine orange/ethidium bromide (AO/EtBr) staining, DNA fragmentation assay, as well as quantitatively by Annexin V/PI double staining and cell cycle analysis. These compounds inhibited growth and proliferation of the MCF-7 cells in a dose- and time-dependent manner. The IC50 values of P.P, TPM.P, 4-CP.P and 3-NP.P after 24 h of exposure were calculated 100 ±5.0, 180 ±6.0, 60 ±4.0 and 140 ±5.0 μM, respectively. 4-CP.P was determined as stronger compound and was chosen for further studies. The result of flow cytometric cell cycle analysis indicated an increase in sub-G1 population after 72 h treatment of the cells. Furthermore, it was accompanied with exposure of phosphatidylserine (PS) in the outer cell membrane after time course of treatment with the 4-CP.P. Based on these observations, the pyrano [3, 2-c] pyridines can be regarded as a valuable candidate for further pharmaceutical evaluations.Anti-cancer activities of some pyrano-pyridines have been previously reported. Herein, we investigated anti-proliferative and apoptotic effects of the novel pyrano [3, 2-c] pyridine (P.P, TPM.P, 4-CP.P and 3-NP.P) compounds against MCF-7 breast cancer cells. The MCF-7 cells were cultured in the presence of various concentrations (20-200 μM) of the compounds for 3 days and the cell viability was determined by MTT assay. Induction of apoptosis was qualitatively assayed by acridine orange/ethidium bromide (AO/EtBr) staining, DNA fragmentation assay, as well as quantitatively by Annexin V/PI double staining and cell cycle analysis. These compounds inhibited growth and proliferation of the MCF-7 cells in a dose- and time-dependent manner. The IC50 values of P.P, TPM.P, 4-CP.P and 3-NP.P after 24 h of exposure were calculated 100 ±5.0, 180 ±6.0, 60 ±4.0 and 140 ±5.0 μM, respectively. 4-CP.P was determined as stronger compound and was chosen for further studies. The result of flow cytometric cell cycle analysis indicated an increase in sub-G1 population after 72 h treatment of the cells. Furthermore, it was accompanied with exposure of phosphatidylserine (PS) in the outer cell membrane after time course of treatment with the 4-CP.P. Based on these observations, the pyrano [3, 2-c] pyridines can be regarded as a valuable candidate for further pharmaceutical evaluations.

Synthesis and Biological Evaluation of Novel Heterocyclic Imines Linked Coumarin- Thiazole Hybrids as Anticancer Agents

2019 ◽  
Vol 19 (4) ◽  
pp. 557-566 ◽  
Author(s):  
Nerella S. Goud ◽  
Mahammad S. Ghouse ◽  
Jatoth Vishnu ◽  
Jakkula Pranay ◽  
Ravi Alvala ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Membrane Potential ◽  
Fluorescence Spectroscopy ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Annexin V ◽  
Biological Evaluation ◽  
Dependent Manner ◽  
Dapi Staining ◽  
Dose Dependent

Background: Human Galectin-1, a protein of lectin family showing affinity towards β-galactosides has emerged as a critical regulator of tumor progression and metastasis, by modulating diverse biological events including homotypic cell aggregation, migration, apoptosis, angiogenesis and immune escape. Therefore, galectin-1 inhibitors might represent novel therapeutic agents for cancer. Methods: A new series of heterocyclic imines linked coumarin-thiazole hybrids (6a-6r) was synthesized and evaluated for its cytotoxic potential against a panel of six human cancer cell lines namely, lung (A549), prostate (DU-145), breast (MCF-7 & MDA-MB-231), colon (HCT-15 & HT-29) using MTT assay. Characteristic apoptotic assays like DAPI staining, cell cycle, annexin V and Mitochondrial membrane potential studies were performed for the most active compound. Furthermore, Gal-1 inhibition was confirmed by ELISA and fluorescence spectroscopy. Results: Among all, compound 6g 3-(2-(2-(pyridin-2-ylmethylene) hydrazineyl) thiazol-4-yl)-2H-chromen-2- one exhibited promising growth inhibition against HCT-15 colorectal cancer cells with an IC50 value of 1.28 ± 0.14 µM. The characteristic apoptotic morphological features like chromatin condensation, membrane blebbing and apoptotic body formation were clearly observed with compound 6g on HCT-15 cells using DAPI staining studies. Further, annexin V-FITC/PI assay confirmed effective early apoptosis induction by treatment with compound 6g. Loss of mitochondrial membrane potential and enhanced ROS generation were confirmed with JC-1 and DCFDA staining method, respectively by treatment with compound 6g, suggesting a possible mechanism for inducing apoptosis. Moreover, flow cytometric analysis revealed that compound 6g blocked G0/G1 phase of the cell cycle in a dose-dependent manner. Compound 6g effectively reduced the levels of Gal-1 protein in a dose-dependent manner. The binding constant (Ka) of 6g with Gal-1 was calculated from the intercept value which was observed as 1.9 x 107 M-1 by Fluorescence spectroscopy. Molecular docking studies showed strong interactions of compound 6g with Gal-1 protein. Conclusion: Our studies demonstrate the anticancer potential and Gal-1 inhibition of heterocyclic imines linked coumarin-thiazole hybrids.

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