Ir J Med Sci (2014) 183:687–688 DOI 10.1007/s11845-014-1171-7
LETTER TO THE EDITOR
Caffeine and its rapidly expanding role in the pathogenesis of malignancies J.-L. Xu • R. Xia
Received: 6 May 2014 / Accepted: 5 July 2014 / Published online: 12 July 2014 Ó Royal Academy of Medicine in Ireland 2014
Dear Sir, With great interest, we read the recent article by El et al. [1] published in a recent issue of your esteemed journal. The authors have clearly illustrated that the long-term administration of caffeine can promote cardiac intrinsic performance and improve the cardiovascular function in the aged rats. To date, caffeine is a natural purine alkaloid present in coffee, tea, and cocoa, which may well be the most widely consumed psychoactive substance in the world [2]. Caffeine is believed to possess different pharmacological functions. Interestingly, the past few years have seen the significant and rapidly expanding role that caffeine has to play in the growth and progression of a number of systemic malignancies. Attenuation of tumor growth has been seen in hepatic malignancies. Caffeine mediates these anti-neoplastic effects by the alternative splicing of the target genes of serine/arginine-rich splicing factor 3 within the tumor cells [3]. Simultaneous reduction of p53a expression is seen. The expression level of p53b is attenuated at the same time. Subsequently, intratumoral apoptosis is markedly accentuated. In addition, caffeine can inhibit tumor growth by direct targeting the PI3 K/Akt signaling pathway [4]. Furthermore, it is reported that PCNA is a significant
J.-L. Xu R. Xia (&) Department of Stomatology, The Second Hospital of Anhui Medical University, Hefei, China e-mail: [email protected] J.-L. Xu e-mail: [email protected]
regulator of the cell cycle in the hepatocellular carcinoma while GST-P has been used as a reliable tumor marker for hepatocellular carcinoma. Caffeine also has an activating effect on the expression of proliferating cell nuclear antigen (PCNA) and glutathione S-transferase (GST)-P [5]. These changes have recently been confirmed in the diethylnitrosamine-induced hepatocarcinogenic rat model. In breast malignancies, it is well known that cancerassociated fibroblasts (CAFs), constituting a major portion of the reactive tumor stroma, play roles in tumor growth, invasion and metastasis. For instance, Al-Ansari et al. [2] in a recent study reveal that caffeine can suppress the migration and invasiveness of CAF cells. It mediates these effects by virtue of inactivation of PTEN-dependent Akt/ Erk1/2 signaling pathway. Furthermore, caffeine also can inhibit the paracrine pro-angiogenic effect of CAF cells by modulating HIF-1a and its downstream VEGF-A. In fact, caffeine shows synergistic activity when administrated along with agents such as cisplatin [6]. Similarly, in the glioma, caffeine can induce the tumor cell death partly by accentuating eIF-2a phosphorylation and decreasing cyclin-D1 expression as well as increasing caspase-dependent and caspase-independent apoptosis pathways [7]. Similarly, in colorectal malignancies, caffeine can inhibit paclitaxel-induced apoptosis through the upregulation of Mcl1, a downstream target of the MEK/ ERK signaling pathway [8]. These changes are clearly seen in Colo205 cancer cell lines. The above examples clearly illustrate the significant antineoplastic effects of caffeine and the need for further studies. Acknowledgments
This work was not supported by any grants.
Conflict of interest
We declare that we have no conflict of interest.
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References 1. El AS, Seif AA (2014) Cardiovascular effects of long-term caffeine administration in aged rats. Ir J Med Sci. doi:10.1007/ s11845-014-1098-z 2. Al-Ansari MM, Aboussekhra A (2014) Caffeine mediates sustained inactivation of breast cancer-associated myofibroblasts via up-regulation of tumor suppressor genes. PLoS ONE 9:e90907. doi:10.1371/journal.pone.0090907 3. Lu GY, Huang SM, Liu ST, Liu PY, Chou WY, Lin WS (2014) Caffeine induces tumor cytotoxicity via the regulation of alternative splicing in subsets of cancer-associated genes. Int J Biochem Cell Biol 47:83–92 4. Edling CE, Selvaggi F, Ghonaim R, Maffucci T, Falasca M (2014) Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway. Cancer Biol Ther 15:524–532
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Ir J Med Sci 5. Fujise Y, Okano J, Nagahara T, Abe R, Imamoto R, Murawaki Y (2012) Preventive effect of caffeine and curcumin on hepatocarcinogenesis in diethylnitrosamine-induced rats. Int J Oncol 40:1779–1788 6. Niknafs B (2011) Induction of apoptosis and non-apoptosis in human breast cancer cell line (MCF-7) by cisplatin and caffeine. Iran Biomed J 15:130–133 7. Chen JC, Hwang JH, Chiu WH, Chan YC (2014) Tetrandrine and caffeine modulated cell cycle and increased glioma cell death via caspase-dependent and caspase-independent apoptosis pathways. Nutr Cancer 16:1–7 8. Mhaidat NM, Alzoubi KH, Al-Azzam SI, Alsaad AA (2014) Caffeine inhibits paclitaxelinduced apoptosis in colorectal cancer cells through the upregulation of Mcl1 levels. Mol Med Rep 9:243–248
LETTER TO THE EDITOR
Caffeine and its rapidly expanding role in the pathogenesis of malignancies J.-L. Xu • R. Xia
Received: 6 May 2014 / Accepted: 5 July 2014 / Published online: 12 July 2014 Ó Royal Academy of Medicine in Ireland 2014
Dear Sir, With great interest, we read the recent article by El et al. [1] published in a recent issue of your esteemed journal. The authors have clearly illustrated that the long-term administration of caffeine can promote cardiac intrinsic performance and improve the cardiovascular function in the aged rats. To date, caffeine is a natural purine alkaloid present in coffee, tea, and cocoa, which may well be the most widely consumed psychoactive substance in the world [2]. Caffeine is believed to possess different pharmacological functions. Interestingly, the past few years have seen the significant and rapidly expanding role that caffeine has to play in the growth and progression of a number of systemic malignancies. Attenuation of tumor growth has been seen in hepatic malignancies. Caffeine mediates these anti-neoplastic effects by the alternative splicing of the target genes of serine/arginine-rich splicing factor 3 within the tumor cells [3]. Simultaneous reduction of p53a expression is seen. The expression level of p53b is attenuated at the same time. Subsequently, intratumoral apoptosis is markedly accentuated. In addition, caffeine can inhibit tumor growth by direct targeting the PI3 K/Akt signaling pathway [4]. Furthermore, it is reported that PCNA is a significant
J.-L. Xu R. Xia (&) Department of Stomatology, The Second Hospital of Anhui Medical University, Hefei, China e-mail: [email protected] J.-L. Xu e-mail: [email protected]
regulator of the cell cycle in the hepatocellular carcinoma while GST-P has been used as a reliable tumor marker for hepatocellular carcinoma. Caffeine also has an activating effect on the expression of proliferating cell nuclear antigen (PCNA) and glutathione S-transferase (GST)-P [5]. These changes have recently been confirmed in the diethylnitrosamine-induced hepatocarcinogenic rat model. In breast malignancies, it is well known that cancerassociated fibroblasts (CAFs), constituting a major portion of the reactive tumor stroma, play roles in tumor growth, invasion and metastasis. For instance, Al-Ansari et al. [2] in a recent study reveal that caffeine can suppress the migration and invasiveness of CAF cells. It mediates these effects by virtue of inactivation of PTEN-dependent Akt/ Erk1/2 signaling pathway. Furthermore, caffeine also can inhibit the paracrine pro-angiogenic effect of CAF cells by modulating HIF-1a and its downstream VEGF-A. In fact, caffeine shows synergistic activity when administrated along with agents such as cisplatin [6]. Similarly, in the glioma, caffeine can induce the tumor cell death partly by accentuating eIF-2a phosphorylation and decreasing cyclin-D1 expression as well as increasing caspase-dependent and caspase-independent apoptosis pathways [7]. Similarly, in colorectal malignancies, caffeine can inhibit paclitaxel-induced apoptosis through the upregulation of Mcl1, a downstream target of the MEK/ ERK signaling pathway [8]. These changes are clearly seen in Colo205 cancer cell lines. The above examples clearly illustrate the significant antineoplastic effects of caffeine and the need for further studies. Acknowledgments
This work was not supported by any grants.
Conflict of interest
We declare that we have no conflict of interest.
123
688
References 1. El AS, Seif AA (2014) Cardiovascular effects of long-term caffeine administration in aged rats. Ir J Med Sci. doi:10.1007/ s11845-014-1098-z 2. Al-Ansari MM, Aboussekhra A (2014) Caffeine mediates sustained inactivation of breast cancer-associated myofibroblasts via up-regulation of tumor suppressor genes. PLoS ONE 9:e90907. doi:10.1371/journal.pone.0090907 3. Lu GY, Huang SM, Liu ST, Liu PY, Chou WY, Lin WS (2014) Caffeine induces tumor cytotoxicity via the regulation of alternative splicing in subsets of cancer-associated genes. Int J Biochem Cell Biol 47:83–92 4. Edling CE, Selvaggi F, Ghonaim R, Maffucci T, Falasca M (2014) Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway. Cancer Biol Ther 15:524–532
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Ir J Med Sci 5. Fujise Y, Okano J, Nagahara T, Abe R, Imamoto R, Murawaki Y (2012) Preventive effect of caffeine and curcumin on hepatocarcinogenesis in diethylnitrosamine-induced rats. Int J Oncol 40:1779–1788 6. Niknafs B (2011) Induction of apoptosis and non-apoptosis in human breast cancer cell line (MCF-7) by cisplatin and caffeine. Iran Biomed J 15:130–133 7. Chen JC, Hwang JH, Chiu WH, Chan YC (2014) Tetrandrine and caffeine modulated cell cycle and increased glioma cell death via caspase-dependent and caspase-independent apoptosis pathways. Nutr Cancer 16:1–7 8. Mhaidat NM, Alzoubi KH, Al-Azzam SI, Alsaad AA (2014) Caffeine inhibits paclitaxelinduced apoptosis in colorectal cancer cells through the upregulation of Mcl1 levels. Mol Med Rep 9:243–248
