scholarly journals SYNERGISTIC GROWTH INHIBITORY EFFECT OF FLAVONOL–KAEMPFEROL AND CONVENTIONAL CHEMOTHERAPEUTIC DRUGS ON CANCER CELLS

2017 ◽  
Vol 9 (2) ◽  
pp. 123 ◽  
Author(s):  
Chepuri Kalyani ◽  
Mangamoori Lakshmi Narasu ◽  
Yumnum Priyadarshini Devi
Keyword(s):  
Growth Inhibition ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Apoptotic Cell ◽  
Inhibitory Effect ◽  
Chemotherapeutic Drugs ◽  
Growth Inhibitory Effect ◽  
Growth Inhibitory

<p><strong>Objective: </strong>The objective of the present study was to evaluate synergistic growth inhibitory effect of a flavonol, kaempferol in combination with chemotherapeutic drugs doxorubicin or cisplatin.</p><p><strong>Methods: </strong>The anti-proliferative activities of kaempferol, doxorubicin and cisplatin on human colorectal cancer cells (HCT-15) and human breast cancer (MDA MB 231) were analyzed by 3-(4,5-dimehylthiaol-2-yl)-2,5-diphenyltetraolium bromide (MTT) assay. Further, combinational studies were performed in both the cell lines to evaluate the interaction of drugs with kaempferol. The combination index (CI) method was used to assess the synergism of kaempferol with doxorubicin or cisplatin. Finally, morphological alterations associated with apoptosis were examined under fluorescent microscope.</p><h1>Results: All compounds showed dose-dependent growth inhibition in both HCT-15 and MDA MB 231 cells. The phytochemical kaempferol showed fifty percent inhibitory concentrations (IC<sub>50</sub>) at 120±3.2 µg/ml and 64±1.2 µg/ml on HCT-15 and MDA MB 231 respectively. IC<sub>50 </sub>concentrations of doxorubicin and cisplatin on both the cell lines were achieved at 49.6±0.5 µg/ml, 25.4±2.9 µg/ml and 44±1.8 µg/ml, 40.6±0.8 µg/ml respectively. Further, <em>in vitro </em>therapeutic effect (IC<sub>50</sub>) of doxorubicin and cisplatin in terms of cell growth inhibition on HCT-15 cells were achieved at their one-fifth (10±0.83 µg/ml) and half (10±1.34 µg/ml) concentrations respectively when they were combined with 30 µg/ml of kaempferol individually. Simultaneously, on MDA-MB 231 cell line, the IC<sub>50</sub> concentrations were reduced to 18±1.22 µg/ml and 15±1.87 µg/ml respectively in combination with 32 µg/ml of kaempferol. The combinational index studies revealed the synergistic association of kaempferol with doxorubicin and cisplatin individually in each cell line. The fluorescence imaging studies strongly supported the synergistic association between kaempferol and doxorubicin or cisplatin by confirming significant apoptotic cell death in both the cell lines which was ~3 fold higher than each agent alone.</h1><p><strong>Conclusion: </strong>The study reveals<strong> </strong>the prominent synergism between the phytochemical, kaempferol and chemotherapeutic drugs doxorubicin or cisplatin which helps in elevating the therapeutic efficacy of drugs.</p>

Enforced CD19 Expression Leads to Growth Inhibition and Reduced Tumorigenicity

Blood ◽  
1999 ◽  
Vol 94 (10) ◽  
pp. 3551-3558 ◽  
Author(s):  
Maged S. Mahmoud ◽  
Ryuichi Fujii ◽  
Hideaki Ishikawa ◽  
Michio M. Kawano
Keyword(s):  
Growth Inhibition ◽  
Cell Line ◽  
Myeloma Cell ◽  
Inhibitory Effect ◽  
Myeloma Cell Line ◽  
Growth Inhibitory Effect ◽  
Myeloma Cells ◽  
Growth Inhibitory ◽  
Human Myeloma Cell Line

In multiple myeloma (MM), the cell surface protein, CD19, is specifically lost while it continues to be expressed on normal plasma cells. To examine the biological significance of loss of CD19 in human myeloma, we have generated CD19 transfectants of a tumorigenic human myeloma cell line (KMS-5). The CD19 transfectants showed slower growth rate in vitro than that of control transfectants. They also showed a lower capability for colony formation as evaluated by anchorage-independent growth in soft agar assay. The CD19 transfectants also had reduced tumorigenicity in vivo when subcutaneously implanted into severe combined immunodeficiency (SCID)-human interleukin-6 (hIL-6) transgenic mice. The growth-inhibitory effect was CD19-specific and probably due to CD19 signaling because this effect was not observed in cells transfected with a truncated form of CD19 that lacks the cytoplasmic signaling domain. The in vitro growth-inhibitory effect was confirmed in a nontumorigenic human myeloma cell line (U-266). However, introduction of the CD19 gene into a human erythroleukemia cell line (K-562) also induced growth inhibition, suggesting that this effect is CD19-specific, but not restricted to myeloma cells. These data suggest that the specific and generalized loss of CD19 in human myeloma cells could be an important factor contributing to the proliferation of the malignant plasma cell clones in this disease.

scholarly journals BP-M345, a New Diarylpentanoid with Promising Antimitotic Activity

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7139
Author(s):  
Pedro Novais ◽  
Patrícia M. A. Silva ◽  
Joana Moreira ◽  
Andreia Palmeira ◽  
Isabel Amorim ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Spindle Assembly Checkpoint ◽  
Human Cancer ◽  
Antitumor Agent ◽  
Inhibitory Effect ◽  
Growth Inhibitory Effect ◽  
Human Cancer Cells ◽  
Antimitotic Activity ◽  
Growth Inhibitory

Previously, we reported the in vitro growth inhibitory effect of diarylpentanoid BP-M345 on human cancer cells. Nevertheless, at that time, the cellular mechanism through which BP-M345 exerts its growth inhibitory effect remained to be explored. In the present work, we report its mechanism of action on cancer cells. The compound exhibits a potent tumor growth inhibitory activity with high selectivity index. Mechanistically, it induces perturbation of the spindles through microtubule instability. As a consequence, treated cells exhibit irreversible defects in chromosome congression during mitosis, which induce a prolonged spindle assembly checkpoint-dependent mitotic arrest, followed by massive apoptosis, as revealed by live cell imaging. Collectively, the results indicate that the diarylpentanoid BP-M345 exerts its antiproliferative activity by inhibiting mitosis through microtubule perturbation and causing cancer cell death, thereby highlighting its potential as antitumor agent.

scholarly journals Preclinical Evaluation of the Pan-FGFR Inhibitor LY2874455 in FRS2-Amplified Liposarcoma

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 189 ◽  
Author(s):  
Robert Hanes ◽  
Else Munthe ◽  
Iwona Grad ◽  
Jianhua Han ◽  
Ida Karlsen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Xenograft Model ◽  
Inhibitory Effect ◽  
Growth Inhibitory Effect ◽  
Growth Inhibitory ◽  
Signaling Components ◽  
Fgfr Inhibition ◽  
Model Expression

Background: FGFR inhibition has been proposed as treatment for dedifferentiated liposarcoma (DDLPS) with amplified FRS2, but we previously only demonstrated transient cytostatic effects when treating FRS2-amplified DDLPS cells with NVP-BGJ398. Methods: Effects of the more potent FGFR inhibitor LY2874455 were investigated in three DDLPS cell lines by measuring effects on cell growth and apoptosis in vitro and also testing efficacy in vivo. Genome, transcriptome and protein analyses were performed to characterize the signaling components in the FGFR pathway. Results: LY2874455 induced a stronger, longer-lasting growth inhibitory effect and moderate level of apoptosis for two cell lines. The third cell line, did not respond to FGFR inhibition, suggesting that FRS2 amplification alone is not sufficient to predict response. Importantly, efficacy of LY2874455 was confirmed in vivo, using an independent FRS2-amplified DDLPS xenograft model. Expression of FRS2 was similar in the responding and non-responding cell lines and we could not find any major difference in downstream FGFR signaling. The only FGF expressed by unstimulated non-responding cells was the intracellular ligand FGF11, whereas the responding cell lines expressed extracellular ligand FGF2. Conclusion: Our study supports LY2874455 as a better therapy than NVP-BGJ398 for FRS2-amplified liposarcoma, and a clinical trial is warranted.

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