Carvedilol suppresses migration and invasion of malignant breast cells by inactivating Src involving cAMP/PKA and PKCδ signaling pathway

Gao, Dezong; Ma, Zhigui; Fu, Qinye; Yu, Zhengping

doi:10.4103/0973-1482.137664

Cited by 21 publications

(7 citation statements)

References 31 publications

(51 reference statements)

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“…Based on the above studies, besides the standard use of βblockers in medical indications, like cardiac arrhythmias, hypertension, infantile hemangioma, thyrotoxicosis, tremors, migraine prophylaxis, cluster or tension headache, β-blockers have emerged as a significant repurposing agent in oncology due to its ability to abrogate the adrenergic signaling pathway via its anti-proliferative, anti-angiogenic, anti-lymphangiogenic, pro-apoptotic, and immunomodulating effects. There is some preclinical data for anti-cancer efficacy for carvedilol and atenolol [196][197][198]; however, most of the preclinical studies have used propranolol. In clinical practice, the frequently prescribed non-selective β-blockers are carvedilol, labetalol, nadolol, and sotalol for non-oncologic reasons as discussed above.…”

Section: Clinical Studies Using Pharmacological Blockadementioning

confidence: 99%

Stress reduction strategies in breast cancer: review of pharmacologic and non-pharmacologic based strategies

et al. 2020

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Breast cancer is the most common cancer diagnosed in women. It is associated with multiple symptoms in both patients and caregivers, such as stress, anxiety, depression, sleep disturbance, and fatigue. Stress appears to promote cancer progression via activation of the sympathetic nervous system releasing epinephrine and norepinephrine as well as activation of hypothalamic-pituitary-adrenal axis releasing cortisol. These stress hormones have been shown to promote the proliferation of cancer cells. This review focuses on stress-reducing strategies which may decrease cancer progression by abrogating these pathways, with a main focus on the β-adrenergic signaling pathway. Patients utilize both non-pharmacologic and pharmacologic strategies to reduce stress. Non-pharmacologic stress-reduction strategies include complementary and alternative medicine techniques, such as meditation, yoga, acupuncture, exercise, use of natural products, support groups and psychology counseling, herbal compounds, and multivitamins. Pharmacologic strategies include abrogating the β2-adrenergic receptor signaling pathway to antagonize epinephrine and norepinephrine action on tumor and immune cells. β-Blocker drugs may play a role in weakening the pro-migratory and pro-metastatic effects induced by stress hormones in cancer and strengthening the anti-tumor immune response. Preclinical models have shown that non-selective β1/2-blocker use is associated with a decrease in tumor growth and metastases and clinical studies have suggested their positive impact on decreasing breast cancer recurrence and mortality. Thus, non-pharmacological approaches, along with pharmacological therapies part of clinical trials are available to cancer patients to reduce stress, and have promise to break the cycle of cancer and stress.

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Section: Clinical Studies Using Pharmacological Blockadementioning

confidence: 99%

Stress reduction strategies in breast cancer: review of pharmacologic and non-pharmacologic based strategies

et al. 2020

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“…In this respect PRO has a similar selectivity to some other clinically used beta-blocker drugs, particularly pindolol and carvedilol and there exists some evidence that these particular drugs may also have potential in repurposing [92–93]. There are a number of distinct putative mechanisms of action that have been investigated in relation to the anticancer effects of PRO, many of them associated with the beta2-adrenoreceptor pathway and which may be particularly important in the context of the metastatic process [94].…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Repurposing Drugs in Oncology (ReDO)—Propranolol as an anti-cancer agent

Pantziarka

Bouche

Sukhatme³

et al. 2016

ecancer

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Propranolol (PRO) is a well-known and widely used non-selective beta-adrenergic receptor antagonist (beta-blocker), with a range of actions which are of interest in an oncological context. PRO displays effects on cellular proliferation and invasion, on the immune system, on the angiogenic cascade, and on tumour cell sensitivity to existing treatments. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. In particular there is evidence that PRO is effective at multiple points in the metastatic cascade, particularly in the context of the post-surgical wound response. Based on this evidence the case is made for further clinical investigation of the anticancer effects of PRO, particularly in combination with other agents. A number of trials are on-going, in different treatment settings for various cancers.

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“…Results from a pre-clinical study indicated that CAR could inhibit the proliferation of cancer cells and induce cell apoptosis in vitro (4). Our previous study identified that CAR significantly decreased the migratory and invasive capacities of breast cancer cells (5). Furthermore, a population-based cohort study indicated that long-term treatment with CAR was associated with a decreased risk of cancer, indicating that CAR may be a potential agent in the prevention of certain types of cancer (6).…”

Section: Introductionmentioning

confidence: 99%

Carvedilol suppresses malignant proliferation of mammary epithelial cells through inhibition of the ROS‑mediated PI3K/AKT signaling pathway

Liu

Zhang

et al. 2018

Oncol Rep

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Reactive oxygen species (ROS) cause oncogenic mutations through direct interaction with DNA. Carvedilol (CAR) exhibits antioxidative activity, and pre-clinical studies have identified that CAR may prevent malignant transformation in certain carcinogenic models. This suggests that CAR may be a potential agent in cancer prevention. In the present study, non-cancerous MCF-10A cells were used as a model to investigate the chemopreventive effect of CAR on benzo(a)pyrene (BaP)-induced cellular carcinogenesis. It was identified that CAR had the ability to eliminate BaP-induced ROS production and subsequent DNA damage. CAR/BaP activated the ROS-mediated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)Thr308 signaling pathway, whereas the effectors of the PI3K/AKT signaling pathway, murine double minute 2 (MDM2) and p53Ser15, served important functions in the BaP/CAR-mediated MCF10A cellular transformation. The results of the present study indicated that CAR may be a novel chemopreventive agent, notably in the prevention of estrogen receptor-negative breast cancer. The antioxidant effects of CAR may contribute to its chemopreventive activity.

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Carvedilol suppresses migration and invasion of malignant breast cells by inactivating Src involving cAMP/PKA and PKCδ signaling pathway

Abstract: CAR was an anti-metastatic agent, which targets Src involving cAMP/PKA or PKCδ pathway in malignant breast cells.

Cited by 21 publications

References 31 publications

Stress reduction strategies in breast cancer: review of pharmacologic and non-pharmacologic based strategies

Stress reduction strategies in breast cancer: review of pharmacologic and non-pharmacologic based strategies

Repurposing Drugs in Oncology (ReDO)—Propranolol as an anti-cancer agent

Carvedilol suppresses malignant proliferation of mammary epithelial cells through inhibition of the ROS‑mediated PI3K/AKT signaling pathway

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