Effects of lapatinib on cell proliferation and apoptosis in NB4 cells

Liu, Lu; Liu, Zhong; Zhao, Yi; Chen, Min; Yao, Shifei; Li, Lianwen; Xiao, Chunlan; Shan, Zhiling; Gan, Liugen; Xu, Ting; Liu, Beizhong

doi:10.3892/ol.2017.7342

Cited by 6 publications

(5 citation statements)

References 33 publications

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“…In line with our findings, several studies have demonstrated the apoptotic behavior of quinazoline derivatives through upregulating the proapoptotic genes and downregulating the antiapoptotic genes [33][34][35]. In particular, quinazoline-based anticancer drugs such as lapatinib and gefitinib were found to inhibit cancer cells growth through increasing the Bax and caspases gene levels and downregulating Bcl-2 levels, which is consistent with our finding in this study [36,37]. RT-PCR analysis of apoptotic related genes.…”

Section: Effect Of Compounds 4d and 4f On Apoptosis Regulatory Markerssupporting

confidence: 92%

The Antiproliferative and Apoptotic Effects of a Novel Quinazoline Carrying Substituted-Sulfonamides: In Vitro and Molecular Docking Study

et al. 2022

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In order to investigate for a new effective and safe anticancer drug, we synthesized a novel series of quinazoline containing biologically active substituted-sulfonamide moiety at 3- position 4a–n. The structure of the newly prepared compounds was proved by microanalysis, IR, 1H-NMR, 13C-NMR and mass spectral data. All the synthesized compounds were evaluated for their in vitro cytotoxic activity in numerous cancer cell lines including A549, HepG-2, LoVo and MCF-7 and normal HUVEC cell line. The two most active compounds 4d and 4f were then tested for their apoptosis induction using DNA content and Annexin V-FITC/PI staining. Moreover, apoptosis initiation was also confirmed using RT-PCR and Western blot. To further understand the binding preferences of quinazoline sulfonamides, docking simulations were used. Among the fourteen new synthesized compounds, we found that compounds 4d and 4f exerted the strongest cytotoxicity against MCF-7 cells with an IC50 value of 2.5 and 5 μM, respectively. Flow cytometry data revealed the ability of compounds 4d and 4f to mediate apoptosis and arrest cell cycle growth at G1 phase. Furthermore, RT-PCR and Western blot results suggested that both 4d and 4f activates apoptotic cell death pathway in MCF-7 cells. Molecular docking assessments indicated that compounds 4d and 4f fit perfectly into Bcl2’s active site. Based on the biological properties, we conclude that both compounds 4d and 4f could be used as a new type of anticancer agent, which provides a scientific basis for further research into the treatment of cancer.

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Section: Effect Of Compounds 4d and 4f On Apoptosis Regulatory Markerssupporting

confidence: 92%

The Antiproliferative and Apoptotic Effects of a Novel Quinazoline Carrying Substituted-Sulfonamides: In Vitro and Molecular Docking Study

et al. 2022

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“…The former is approved for 2-year-old children and older in relapsed APL expressing CD33, whereas tamibarotene is still under investigation. Small molecule inhibitors with targets such as tyrosine kinases, telomerase, and c-myc have demonstrated some efficacy in preclinical studies using APL cell lines but have not yet advanced to clinical trials [70][71][72][73].…”

Section: Treatment Advancesmentioning

confidence: 99%

Advances in Pediatric Acute Promyelocytic Leukemia

Conneely¹,

Stevens²

2020

Children

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Acute promyelocytic leukemia (APL) is a rare disease accounting for only 5%–10% of pediatric acute myeloid leukemia (AML) and fewer than 1000 cases occur annually in the United States across all age groups. Characterized by t (15; 17), with a resultant PML-RARA gene fusion driving leukemia development, advances in therapy have improved outcomes for APL significantly in the past several decades, now making APL the most curable form of AML in both children and adults. Cure rates in APL are now comparable to pediatric B-lymphoid leukemias. The success of APL treatment is due, in part, to the breadth of understanding of the driver PML-RARA mutation as well as collaborative efforts to quickly introduce and maximize the benefit of new therapies. Here, we review the presentation, clinical features, pathogenesis, and treatment advances in pediatric APL.

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“…Consistent with other reports [52,53], we observed that Tz, T-DM1, and Lp decreased cell viability in both cell lines. It has been evidenced that the mechanism of cell viability inhibition by anti-HER2 drugs results from cell cycle arrest and increased apoptosis [54][55][56]. We noted that Tz and T-DM1, administered as a single agent, produced minimal inhibition, but their combination with Lp resulted in a potentiated effect.…”

Section: Discussionmentioning

confidence: 73%

Potential Biomarkers Associated with Prognosis and Trastuzumab Response in HER2+ Breast Cancer

Castro-Guijarro,

Sanchez,

Flamini

2023

Cancers

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Breast cancer (BC) is the most common malignancy among women worldwide. Around 15–25% of BC overexpress the human epidermal growth factor receptor 2 (HER2), which is associated with a worse prognosis and shortened disease-free survival. Therefore, anti-HER2 therapies have been developed, such as monoclonal antibodies (trastuzumab, Tz), antibody–drug conjugates (ado-trastuzumab emtansine, T-DM1), and pharmacological inhibitors of tyrosine kinase activity (lapatinib, Lp). Although Tz, the standard treatment, has significantly improved the prognosis of patients, resistance still affects a significant population of women and is currently a major challenge in clinical oncology. Therefore, this study aims to identify potential biomarkers to predict disease progression (prognostic markers) and the efficacy of Tz treatment (predictive markers) in patients with HER2+ BC. We hypothesize that proteins involved in cell motility are implicated in Tz-resistance. We aim to identify alterations in Tz-resistant cells to guide more efficient oncologic decisions. By bioinformatics, we selected candidate proteins and determined how their expression, localization, and the process they modulate were affected by anti-HER2 treatments. Next, using HER2+ BC patients’ data, we assessed these proteins as prognostic and predictive biomarkers. Finally, using Tz-resistant cells, we evaluated their roles in Tz response. We identified deregulated genes associated with cell motility in Tz/T-DM1-resistant vs. -sensitive cells. We showed that Tz, T-DM1, and Lp decrease cell viability, and their effect is enhanced in combinations. We determined synergism between Tz/T-DM1 and Lp, making possible a dose reduction of each drug to achieve the same therapeutic effect. We found that combinations (Tz/T-DM1 + Lp) efficiently inhibit cell adhesion and migration. Furthermore, we demonstrated the induction of FAK nuclear and cortactin peri-nuclear localization after T-DM1, Lp, and Tz/T-DM1 + Lp treatments. In parallel, we observed that combined treatments downregulate proteins essential for metastatic dissemination, such as SRC, FAK, and paxillin. We found that low vinculin (VCL) and cortactin (CTTN) mRNA expression predicts favorable survival rates and has diagnostic value to discriminate between Tz-sensible and Tz-resistant HER2+ BC patients. Finally, we confirmed that vinculin and cortactin are overexpressed in Tz-resistance cells, SKBR3-RTz. Moreover, we found that Tz plus FAK/paxillin/cortactin-silencing reduced cell adhesion/migration capacity in Tz-sensitive and -resistant cells. In conclusion, we demonstrate that combined therapies are encouraging since low doses of Tz/T-DM1 + Lp inhibit metastatic processes by downregulating critical protein expression and affecting its subcellular localization. We propose that vinculin and cortactin might contribute to Tz-sensibility/resistance in BC cells. Finally, we identify potential prognostic and predictive biomarkers that are promising for personalized BC management that would allow efficient patient selection in order to mitigate resistance and maximize the safety and efficacy of anti-HER2 therapies.

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Effects of lapatinib on cell proliferation and apoptosis in NB4 cells

Cited by 6 publications

References 33 publications

The Antiproliferative and Apoptotic Effects of a Novel Quinazoline Carrying Substituted-Sulfonamides: In Vitro and Molecular Docking Study

The Antiproliferative and Apoptotic Effects of a Novel Quinazoline Carrying Substituted-Sulfonamides: In Vitro and Molecular Docking Study

Advances in Pediatric Acute Promyelocytic Leukemia

Potential Biomarkers Associated with Prognosis and Trastuzumab Response in HER2+ Breast Cancer

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