Are Platelets the Primary Target of Aspirin's Remarkable Anticancer Activity?

Lichtenberger, Lenard M.; Vijayan, K. Vinod

doi:10.1158/0008-5472.can-19-0762

Cited by 29 publications

(21 citation statements)

References 20 publications

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“…This coincides with a previous study, which demonstrated that activated platelets increased proliferation of colon cancer in both in vitro and in vivo mouse models, while treatment with aspirin and aspirin-PC decreased platelet counts and activation, which was correlated with decreased tumor burden (24). Platelet effects may account for the apparent effectiveness of aspirin against breast cancer in epidemiological studies despite the minimal direct antitumor effect of the drug in previous in vitro studies, which were performed in the absence of platelets (5,6,39). The authors of the present study aim to investigate the role of platelets and NSAID-induced platelet inhibition in breast cancer in future projects.…”

Section: Discussionsupporting

confidence: 90%

Growth inhibitory effects of PC‑NSAIDs on human breast cancer subtypes in cell culture

Burge

Lichtenberger

2019

Oncol Lett

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The potential role of non-steroidal anti-inflammatory drug (NSAID) therapy in the prevention and treatment of cancer has generated considerable research interest. Phosphatidylcholine (PC)-associated NSAIDs decrease the gastrointestinal side effects of NSAID therapy, and may be more effective than traditional NSAIDs in limiting tumor growth. In the present study, human cells representing three major breast cancer subtypes were cultured with aspirin, indomethacin and PC-associated forms of each drug, with PC alone as a control. All tested drugs decreased the tumor cell number after 8 days of culture, with PC-NSAIDs having the greatest inhibitory effect, and NSAIDs alone, particularly aspirin, having the least effect. PC alone was effective in limiting the proliferation of all cell lines, suggesting that the two components of PC-NSAIDs have an additive effect. The ELISA results did not support a strong role for inhibition of cyclooxygenase enzymes in the decrease in cancer cell proliferation, which may account for the limited effectiveness of aspirin alone. PC-NSAIDs, particularly indomethacin-PC, are attractive candidate drugs in the prevention and treatment of different types of breast cancer, including triple negative breast cancer.

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Section: Discussionsupporting

confidence: 90%

Growth inhibitory effects of PC‑NSAIDs on human breast cancer subtypes in cell culture

Burge

Lichtenberger

2019

Oncol Lett

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“…The anticancer effects of ASA have been previously discussed in the literature, but its actual therapeutic use is still controversial 18,46,47 . More is discussed about a putative chemopreventive action of ASA, such as its use to prevent myocardial infarct, and a reduced incidence of metastasis in cancer patients regularly taking the drug, than a direct effect reducing existent tumors 18,[46][47][48] . The results that we presented here showed that the treatment of mice with ASA, or even its metabolic product, SA, also prevented implanted cancer growth, which is beneficial especially when associated with other therapies.…”

Section: Discussionmentioning

confidence: 99%

“…In the current work, we showed that SA and ASA present anticancer effects against skin melanoma implanted on C57BL6/J mice. The anticancer effects of ASA have been previously discussed in the literature, but its actual therapeutic use is still controversial 18 , 46 , 47 . More is discussed about a putative chemopreventive action of ASA, such as its use to prevent myocardial infarct, and a reduced incidence of metastasis in cancer patients regularly taking the drug, than a direct effect reducing existent tumors 18 , 46 – 48 .…”

Section: Discussionmentioning

confidence: 99%

Acetylsalicylic acid and salicylic acid present anticancer properties against melanoma by promoting nitric oxide-dependent endoplasmic reticulum stress and apoptosis

Ausina

Branco

Demaria

et al. 2020

Sci Rep

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Melanoma is the most aggressive and fatal type of skin cancer due to being highly proliferative. Acetylsalicylic acid (ASA; Aspirin) and salicylic acid (SA) are ancient drugs with multiple applications in medicine. Here, we showed that ASA and SA present anticancer effects against a murine model of implanted melanoma. These effects were also validated in 3D- and 2D-cultured melanoma B16F10 cells, where the drugs promoted pro-apoptotic effects. In both in vivo and in vitro models, SA and ASA triggered endoplasmic reticulum (ER) stress, which culminates with the upregulation of the pro-apoptotic transcription factor C/EBP homologous protein (CHOP). These effects are initiated by ASA/SA-triggered Akt/mTOR/AMPK-dependent activation of nitric oxide synthase 3 (eNOS), which increases nitric oxide and reactive oxygen species production inducing ER stress response. In the end, we propose that ASA and SA instigate anticancer effects by a novel mechanism, the activation of ER stress.

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“…Long-term follow-up studies have shown that regular use of aspirin reduces the long-term risk of several cancers, as well as the risk of distant metastasis. [62][63][64] For lung cancer, the benefit of aspirin was only confirmed in ADC. 25 Anticoagulants are effective for patients with venous thromboembolism.…”

Section: Discussionmentioning

confidence: 99%

<p>Platelet Count is Associated with the Rate of Lymph Node Metastasis in Lung Adenocarcinoma</p>

Qu¹,

Li²,

Tang³

et al. 2020

CMAR

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Purpose: Emerging studies have revealed that platelets are involved in tumor metastasis in lung adenocarcinoma (ADC). The solid pathological subtype of lung ADC is associated with metastasis, recurrence, and poor prognosis. However, there is no study exploring the relationship between platelets and different lung pathological subtypes. Patients and Methods: The association between platelet counts and lymph node metastasis was analyzed in 852 patients with lung ADC who underwent surgery and lymph node dissection. Multivariate logistic analysis was conducted to identify the risk factors of lymph node metastasis. Then, lymph node metastasis and other factors were analyzed to determine their correlation with platelet count and histological subtype. Results: We found that the platelet count was associated with lymph node metastasis (P = 0.01) in multivariable analysis, independent of tumor size, predominant subtype, visceral pleural invasion, and microvessel invasion. In patients with a platelet count ≥300 × 109/L, the rate of lymph node metastasis was 38.5%, almost twice as high as that in patients with a platelet count <300 × 109/L (23.2%). Additionally, elevated platelet counts, even those within the normal range, were significantly associated with a higher rate of lymph node metastasis. The mean platelet count in patients with solid-predominant histology (269.70 ± 69.38 × 109/L) was significantly higher than that in patients with other histologies (P < 0.001). Conclusion: Elevated platelet counts are significantly associated with a higher rate of lymph node metastasis, even if the platelet counts are within the reference range. Platelet counts were significantly higher in patients with solid-predominant histology than in patients with other histologies. In addition, VEGF-C may play an important role in lymphatic metastasis in patients with lung ADC. We hypothesize that antiplatelet therapy may reduce lymph node metastasis in lung ADC patients.

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Are Platelets the Primary Target of Aspirin's Remarkable Anticancer Activity?

Cited by 29 publications

References 20 publications

Growth inhibitory effects of PC‑NSAIDs on human breast cancer subtypes in cell culture

Growth inhibitory effects of PC‑NSAIDs on human breast cancer subtypes in cell culture

Acetylsalicylic acid and salicylic acid present anticancer properties against melanoma by promoting nitric oxide-dependent endoplasmic reticulum stress and apoptosis

<p>Platelet Count is Associated with the Rate of Lymph Node Metastasis in Lung Adenocarcinoma</p>

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