Strong synergism between small molecule inhibitors of HER2, PI3K, mTOR and Bcl-2 in human breast cancer cells

Hamunyela, Roswita; Serafin, Antonio; Akudugu, John

doi:10.1016/j.tiv.2016.10.002

Cited by 8 publications

(4 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression of cyclin D1 is increased in different types of tumor tissues (46). The present results were consistent with these studies (41)(42)(43)(44)(45)(46), which indicated that telmisartan inhibited signaling via the PI3K/AKT pathway in A549 cells, and reduced the phosphorylation of mTOR, p70S6K and cyclin D1. In summary, the downregulation of the PI3K/AKT pathway may have contributed to the inhibitory effect of telmisartan on A549 cells.…”

Section: Discussionsupporting

confidence: 92%

See 1 more Smart Citation

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Zhang

Wang

2018

Oncol Lett

View full text Add to dashboard Cite

Abstract. Expression of angiotensin II (Ang II), a key biological peptide in the renin-angiotensin system, is closely associated with the occurrence and development of cancer. Ang II binds two receptor subtypes, the Ang II type 1 receptor (AT1R) and the AT2R, to mediate a series of biological effects. Telmisartan, a specific AT1R blocker, has been reported to have potential as an anticancer drug for treating renal cancer. In the present study, whether telmisartan had an effect on non-small cell lung cancer (NSCLC) cell proliferation and migration was investigated. The Cell Counting kit-8 assay revealed that telmisartan significantly inhibited the growth of the NSCLC A549 cell line in a time-and dose-dependent manner. In a transwell assay, telmisartan significantly inhibited cellular invasion and migration. Furthermore, it was determined that the expression of the anti-apoptotic protein B-cell lymphoma was decreased, and that of the pro-apoptotic proteins caspase-3 and Bcl-associated X increased in the A549 cells treated with telmisartan. Additionally, levels of phosphorylated RAC serine/threonine-protein kinase (p-AKT), p-mechanistic target of rapamycin, p70-S6 kinase and cyclin D1 was decreased in the telmisartan-treated group. Therefore, the current study reveals that telmisartan-induced NSCLC apoptosis may be regulated via the phosphoinositide 3-kinase/AKT signaling pathway, which indicates that it may be a potential novel drug for clinical NSCLC treatment. IntroductionLung cancer, the most common type of cancer, has the highest morbidity rate among all types of malignancies worldwide (1,2), accounting for 30% of all incidences of cancer-associated mortality (3). In clinical practice, the two major types of lung cancer are small cell lung cancer (SCLC) and non-SCLC (NSCLC) (4), of which NSCLC accounts for ~80% of all lung cancer cases (5). Current therapies for NSCLC include chemotherapy, radiotherapy, targeted therapy and surgery, which are used alone or in combination (6). Despite the use of these therapies, the overall 5-year survival rate of NSCLC remains low, at 15% (7). Owing to the development of drug resistance and the severe side effects experienced by patients, effective and safe novel agents are required for the treatment of NSCLC (1).Angiotensin II (Ang II), a key biological peptide in the renin-angiotensin system, is a vasoconstrictor that controls cardiovascular function and renal homeostasis (8). Ang II receptor blockers (ARBs) are extensively used as anti-hypertensive drugs (9). Studies have reported that angiogenesis is essential for tumor progression and metastasis (10,11). Furthermore, studies have demonstrated that ARBs have the potential possibility to restrain the growth of several types of cancer cells (12,13). Ang II binds two receptor subtypes, the Ang II type 1 receptor (AT1R) and the Ang II type 2 receptor (AT2R), to mediate a series of biological effects (14). AT1R mediates the main functions of Ang II, including tumor growth and angiogenesis (15). Treatment with telmisartan, a spe...

show abstract

Section: Discussionsupporting

confidence: 92%

“…In addition, AKT can phosphorylate Bcl-2, making it resistant to protein degradation and ultimately protecting the cell from apoptosis (41). The effect of mTOR on Bcl-2 is similar to that of AKT (42). Additionally, p70S6K and cyclin D1 may also be involved in pathways that telmisartan effects in cancer cells.…”

Section: Discussionmentioning

confidence: 83%

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Zhang

Wang

2018

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…Before the analysis, the text will be read through several times to obtain a sense of the whole and familiarise with the data. Then word transcript of the data will be imported into NVivo software V.1153 and coded line by line. The codes will be compared based on differences and similarities and sorted into categories, and categories will be grouped in themes.…”

Section: Methodsmentioning

confidence: 99%

Breast and cervical cancer patients’ experience in Addis Ababa city, Ethiopia: a follow-up study protocol

et al. 2019

View full text Add to dashboard Cite

IntroductionCancer is an emerging public health problem in Ethiopia, with breast and cervical cancers accounting for over half of all newly diagnosed cancers in women. The majority of women with breast and cervical cancer are diagnosed at late stage of the disease and most patients do not receive care consistent with global standards. However, little is known about the health-seeking behaviours, barriers to early detection and treatment, patient-reported outcomes, financial burden and survival of women with breast and cervical cancer in the country. Therefore, this study aims to document the experience of women with breast and cervical cancer from recognition of symptoms to diagnosis, treatment and survivorship/mortality in Addis Ababa city, Ethiopia.Methods and analysisA prospective follow-up study using mixed methods (both quantitative and qualitative) will be employed. All women newly diagnosed with breast and cervical cancer from 1 January, 2017 to 30 June 2018 in Addis Ababa will be included in the study. Interviewer-administered questionnaires will be used to collect information about medical consultations after recognition of symptoms, health-seeking behaviours, treatment received, barriers to early detection and treatment, and survivorship care. In-depth interview will be conducted on purposefully selected women with breast and cervical cancer. The primary outcomes of the study are time intervals (patient and diagnostic waiting times), stage at diagnosis and survival. Multivariable analysis will be employed to determine the contributions of independent variables on the outcomes of interest. HRs with 95% CIs will be calculated for time-to-event outcomes. Qualitative data will be analysed using thematic analysis.Ethics and disseminationThis protocol is ethically approved by Institutional Review Board of Addis Ababa University. Verbal informed consent will be obtained from study participants. Results will be disseminated in international peer-reviewed journals and presented in relevant conferences.

show abstract

“…When other mTOR inhibitors, BEX235 or AZD8055, were combined with ABT-263 in vitro , a higher rate of apoptosis was observed, and either one of the mTOR combined inhibitors with navitoclax induced more tumor regression in xenograft models than the drugs alone ( 93 ). The PI3K and mTOR inhibitor (NVP-BEZ235) and ABT-263 combination, even at lower concentrations, also showed strong synergism against breast cancer cells, especially in ER- and PR-negative cells ( 94 ). Induction of BCL-family activity is expected by the mTOR inhibitors, which could sensitize the cell to ABT-263 ( 95 ).…”

Section: Potential Therapeutic Strategiesmentioning

confidence: 99%

Targeting Senescence as a Therapeutic Opportunity for Triple-Negative Breast Cancer

Paula

Kieran

Koh

et al. 2023

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC) is associated with an elevated risk of recurrence and poor prognosis. Historically, only chemotherapy was available as systemic treatment, but immunotherapy and targeted therapies currently offer prolonged benefits. TNBC is a group of diseases with heterogeneous treatment sensitivity, and resistance is inevitable and early for a large proportion of the intrinsic subtypes. Although senescence induction by anticancer therapy offers an immediate favourable clinical outcome once the rate of tumour progression reduces, these cells are commonly dysfunctional and metabolically active, culminating in treatment-resistant repopulation associated with worse prognosis. This heterogeneous response can also occur without therapeutic pressure, in response to damage or oncogenic stress, playing a relevant role in the carcinogenesis. Remarkably, there is pre-clinical and exploratory clinical evidence to support a relevant role of senescence in treatment resistance. Therefore, targeting senescent cells has been a scientific effort in many malignant tumours using a variety of targets and strategies, including increasing pro-apoptotic and decreasing anti-apoptotic stimuli. Despite promising, there are some challenges to applying this technology, including the best schedule of combination, assessment of senescence, specific vulnerabilities, and the best clinical scenarios. This review provides an overview of senescence in TNBC with focus on future-proofing senotherapy strategies.

show abstract

Strong synergism between small molecule inhibitors of HER2, PI3K, mTOR and Bcl-2 in human breast cancer cells

Cited by 8 publications

References 42 publications

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Breast and cervical cancer patients’ experience in Addis Ababa city, Ethiopia: a follow-up study protocol

Targeting Senescence as a Therapeutic Opportunity for Triple-Negative Breast Cancer

Contact Info

Product

Resources

About