Caffeic Acid Phenethyl Ester Effect on Lung Cancer, Breast Cancer, Cervical Cancer

Health disorders result from a variety of risk contributing agents that have strong environmental sources. These agents could be deleterious and lead to cancer. The present description is concerned with highlighting about the effect of Caffeic acid phenethyl ester (CAPE) on Lung, breast and cervical cancer. Briefly, CAPE is a component believed to be obtained from honeybee hive propolis. It is considered as a bioactive, anticarcinogenic or antimitogenic compound with medical significance. It exerts its chemical effects through the NF-κB signaling pathway inhibition (Chuu et al.2012).CAPE has a significant effect on lung cancer. This became apparent when a comparative study evaluated the effect of CAPE on normal lung fibroblast WI-38 cells and human lung cancer A549 cells. It was found that CAPE caused the cytotoxicity, apoptosis, and radio sensitization in A549 cells when they were subjected to treatments at various intervals (Chen et al. 2004).This has strengthened another study where CAPE was found to increase the radio sensitivity in lung cancer by lessening thoracic irradiation induced inflammatory responses. This had shed light on the combined effect of CAPE and thoracic radiotherapy (Chen et al. 2005). In experimental analyses, CAPE was found to reduce tumor nodules formed during lung metastasis when tumor inoculated mice were orally administered with 5 mg/mice/day for 7 days (Nagaoka et al.2003).CAPE interferes with the transforming growth factor-β(TGF-β) induced Akt phosphorylation and suppresses the motility of A549 lung adenocarcinoma cells. Thus, CAPE may also be regarded as a potential anti-metastatic agent.Patients with advancing stage of lung cancer have increased levels of oxidative stress and deceased antioxidant molecules (Esme et al.2008). CAPE was found to deplete the intracellular deposits of glutathione and make cells more vulnerable to oxidative stress-inducedapoptosis (Cotgreave and Gerdes 1998). In a study, radiation induced lung injury was weakened in vivio by the antioxidant effect of CAPE (Oguz Galip et al.2008) This indicates that CAPE could serve as protective antioxidant agent in lung cancer patients. In human lung fibroblasts cell lines (CCD-11Lu ),CAPE was found to inhibit eotaxin secretion stimulated by tumor necrosis factor-alpha (TNF-alpha) and interleukin-13 (IL-13) (Liao et al., 2010). Human lung fibroblasts lead to lung cancer progression when ionizing radiation leads to their senescence (Papadopoulou and Kletsas, 2011). So, it may suggest that lung cancer patients who receive ionization radiation need to be assessed by CAPE.CAPE with antitumor effect is also important for breast cancer. In human breast cancer MCF-7 cells, CAPE induces programmed cell death by NFkappaB inhibition where Fas activation plays a significant role (Watabe et al. 2004).In a study CAPE was found reduce the malignant property of breast cancer stem cells (bCSC) isolated from MDA-231 cells. The changes observed were self renewal inhibition, clonal growth in soft agar medium, formation of progenitors and decrease in CD44 content (Omene,Wu and Frenkel, 2012).CAPE is also considered as natural anti-PAK1 (p21-Activated Protein Kinase) product and could be used to treat PAK1-dependent cancers like breast cancer (Hashimoto et al. 2009).This has strengthened as study where CAPE based propolis extracts were shown to serve as PAK1 remedies for breast cancer by suppressing the development of NF (beurofibromatosis) tumors that rely PAK1 signaling pathway (Messerli et al. 2009).

CAPE was reported to exert multiple effects in a concentration dependant mode in MDA-231 and MCF-7 cells of human breast cancer type. It not only induces apoptosis and NF-κB modification but also alters angiogenesis and cell cycle (Wu et al.2011). CAPE has good specificity for human estrogen receptor beta hERβ and was shown to play role in treating and preventing breast cancer which involves estrogen-related conditions (Jung et al. 2010).

Drugs like Tamoxifen (TAM) recommended for TREATINGBreast cancer were reported to induce hepatotoxicity. However, CAPE could offer protection against TAM induced adverse effects, as observed in female rats. This could occur by antioxidative activity and reduction of inflammation and cellular integrity maintenance (Albukhari et al. 2009).

In addition,the antioxidant property of CAPE was much revealed when it was able to reduce nitric oxide and superoxide dismutase activity in vitro in ZR-75-1 human breast cancer cell line (El-Refaei and El-Naa 2011).The antitumor effect of CAPE further revealed when researchers used the ethanol extracts of CAPE in a dose dependant manner in decreasing the MCF- cell viability which occurred via ER (endolasmic reticulum) –stress related signaling (Kamiya et al.2012). In a reent study, it was found that CAPE could reduce triple-negative breast cancer (TNBC) and breast cancer stem cells when dietary CAPE was fed to nude mice bearing 231 xenograft which were multiplied as mammospheres (Omene et al.2010).

Finally, the effect of CAPE to be dealt is cervical cancer. Briefly, cervical cancer begins in the cells lining the cervix surface. The types of cells present are columnar and squamous. Cervical cancers are mostly related squamous cells (“Cervical cancer” 2012). The major etiological factor identified to cause cervical cancer is human papilloma virus (HPV) infection.Here, oxidative stress was reported to be a contributing factor in in HPV-initiated carcinogenesis. Oxidative stress cold disturb the stauts of cellular redox leads to responses related to altered gene expression via the activation of transcription factors that are redox-sensitive (Domenico et al. 2012)

As CAPE has antioxidant property, pro-apoptotic and imuunomodulatory potentialarlier, its structure analogue CAO was tested in cultured human cells. The compound was able to induce apoptosis by inducing high expression of c-Jun, p21 and p53. This was reported to occur through the activation of caspase-8 and down-regulation of Mcl-1 gene expression (Hung et al. 2003)In connection with this, a study reported that caffeic acid could significantly induce programmed cell death human cervical cancer cells through the mitochondrial pathway (Chang et al. 2010).

Since HPV has is contributing factor for cervical cancer, CAPE effect was much explored in a investigating where CAPE was found to suppress the activity of human HPV18 and 51 transformed cloned rat embryo fibroblast (CREF) cells (Lin et al. 2010).

So, transformed cell growth could be selectively blocked by CAPE which could be easily identified by gene expression changes. This could indicate that CAPE may be useful in identifying the targets for cancer therapeutic interventions. Cervical cancer could be prevented by blocking the HPV-dependant apoptotic regulators like p53 and inhibiting caspase 3 activation and cytochrome c release (Padilla, Leung and Carson 2002). It is important to note that CAPE action is characterized by caspase-3/caspase-7 activation (Chen et al. 2008). So this mechanism when explored would furnish insights whether or not CAPE is exerts compete inhibitory effect cervical cancer.

It appears that the research data on the association between CAPE on cervical cancer is limited. As it has link with HPV, this area of cervical cancer needs further exploration from several corners keeping in view of certain interrelated molecular mechanisms

Therefore, it can be concluded that CAPE exerts a multitude of actions on cellular and genetic network. It has good antitumor properties and has future implications for anticancer therapeutic interventions.

Works Cited

Albukhari, AA, Gashlan, HM, El-Beshbishy, HA, Nagy, AA and Naim Abdel,AB. “Caffeic acid phenethyl ester protects against tamoxifen-induced hepatotoxicity in rats.” Food Chem Toxicol 47.7 (2009):1689-95.Print.

Chang, WC, Hsieh, CH, Hsiao, MW, Lin, WC, Hung, YC an Ye, JC.2010. “Caffeic acid induces apoptosis in human cervical cancer cells through the mitochondrial pathway.”Taiwan J Obstet Gynecol, 49.4 (2010):419-24.Print

Chen, MF, Wu, CT, Chen, YJ, Keng, PC, and Chen WC. “Cell killing and radiosensitization by caffeic acid phenethyl ester (CAPE) in lung cancer cells.” J Radiat Res 45.2 (2004):253-60.Print.

Chen, MF, Wu, CT, Chen, YJ, Keng, PC, and Chen WC. “Caffeic acid phenethyl ester decreases acute pneumonitis after irradiation in vitro and in vivo.” BMC Cancer 5 (2005):158.Print.

Chen, MJ, Chang, WH, Lin, CC, Liu, CY, Wang, TE, Chu, CH, Shih, SC and Chen, YJ. Caffeic acid phenethyl ester induces apoptosis of human pancreatic cancer cells involving caspase and mitochondrial dysfunction. Pancreatology 8.6 ( 2008):566-76.Print

Chuu, CP, Lin, HP, Ciaccio, MF, Kokontis, JM, Hause, RJ, Jr, Hiipakka, RA, Liao, S and Jones, RB. “Caffeic acid phenethyl ester suppresses the proliferation of human prostate cancer cells through inhibition of p70S6K and Akt signaling networks. Cancer Prev Res (Phila) 5.5 (2012):788-97.Print.

Cotgreave IA and Gerdes, RG.Recent trends in glutathione biochemistry–glutathione-protein interactions: a molecular link between oxidative stress and cell proliferation? Biochem Biophys Res Commun 242 (1998):1-9.Print.

Domenico Di, F, Foppoli, C, Coccia, R and Perluigi, M. “Antioxidants in cervical cancer: chemopreventive and chemotherapeutic effects of polyphenols.” Biochim Biophys Acta 1822.5 (2012):737-47.Print

El-Refaei Mohamed, F and El-Naa Mona M. “Antioxidant and Apoptotic Effects of Caffeic Acid Phenethyl Ester Induced Marked Inhibition on Human Breast Cancer Cell Line.” Asian Journal of Biochemistry 6 (2011): 82-89.Print.

Esme, H, Cemek, M, Sezer, M, Saglam, H, Demir, A, Melek, H and Unlu, M.High levels of oxidative stress in patients with advanced lung cancer. Respirology 13.1 (2008):112-6. Print.

Hashimoto Hisashi, Messerl Shanta, M, Sudo Tamotsu and Marut Hiroshi. “Ivermectin inactivates the kinase PAK1 and blocks the PAK1- dependent growth of human ovarian cancer and NF2 tumor cell lines.” Drug Discov Ther 3.6 (2009):243-246.Print.

Hung, MW, Shiao, MS, Tsai, LC, Chang, GG and Chang TC. Apoptotic effect of caffeic acid phenethyl ester and its ester and amide analogues in human cervical cancer ME180 cells. Anticancer Res 23.6C (2003): 4773-80.Print.

Jung, BI, Kim, MS, Kim, HA, Kim, D, Yang, J, Her, S and Song, YS. “Caffeic acid phenethyl ester, a component of beehive propolis, is a novel selective estrogen receptor modulator.” Phytother Res 24.2 (2010):295-300.Print.

Kamiya Tetsuro, Nishihara Hiroko, Hara Hirokazu and Adachi Tetsuo. “Ethanol Extract of Brazilian Red Propolis Induces Apoptosis in Human Breast Cancer MCF‑7 Cells through Endoplasmic Reticulum Stress.” J. Agric. Food Chem 60 (2012):11065−11070.Print.

Liao, YR, Hsu, JY, Chu, JJ and Fu, LS. “Caffeic acid phenethyl ester suppresses the induction of eotaxin in human lung fibroblast cells”. J Asthma 47.3 (2010):233-7.Print.

Lin, J, Su, Z, Grunberger, D, Zimmer, S andFisher P.” Caffeic acid induces apoptosis in human cervical cancer cells through the mitochondrial pathway.” Taiwan J Obstet Gynecol 49.4 (2010):419-24.Print.

Messerli, SM, Ahn, MR, Kunimasa, K, Yanagihara, M, Tatefuji, T, Hashimoto, K, Mautner, V, Uto, Y, Hori, H, Kumazawa, S, Kaji, K, Ohta, T and Maruta, H. “Artepillin C (ARC) in Brazilian green propolis selectively blocks oncogenic PAK1 signaling and suppresses the growth of NF tumors in mice.” Phytother Res 23.3(2009):423-427.Print.

Nagaoka, T, Banskota, AH, Tezuka, Y, Harimaya, Y, Koizumi, K, Saiki, I and Kadota, S. “Inhibitory effects of caffeic acid phenethyl ester analogues on experimental lung metastasis of murine colon 26-L5 carcinoma cells.” Biol Pharm Bull 26.5 (2003):638-41.Print.

Omene,CO, Wu, J, Smith,JA and K. Frenkel. Inhibition of triple-negative breast cancer (TNBC) and breast cancer stem cells (bCSC) by caffeic acid phenethyl ester (CAPE).J Clin Oncol 28, (suppl; abstr e13587).Print.Web.

Omene, CO, Wu, J and Frenkel, K. “Caffeic Acid Phenethyl Ester (CAPE) derived from propolis, a honeybee product, inhibits growth of breast cancer stem cells.” Invest New Drugs 30.4 (2012):1279-88.Print.

Padilla,LA, Leung, BS and Carson LF. Evidence of an association between human papillomavirus and impaired chemotherapy-induced apoptosis in cervical cancer cells. Gynecol Oncol 85.1 (2002):59-66.Print

Papadopoulou, A and Kletsas,D. “Human lung fibroblasts prematurely senescent after exposure to ionizing radiation enhance the growth of malignant lung epithelial cells in vitro and in vivo.” Int J Oncol 39.4 (2011):989-99. Print.

Shigeoka, Y, Igishi, T, Matsumoto, S, Nakanishi, H, Kodani, M, Yasuda, K, Hitsuda, Y, Shimizu, E. “Sulindac sulfide and caffeic acid phenethyl ester suppress the motility of lung adenocarcinoma cells promoted by transforming growth factor-beta through Akt inhibition”.J Cancer Res Clin Oncol 130.3 (2004):146-52. Print.

Watabe, M, Hishikawa, K, Takayanagi, A, Shimizu,N and Nakaki, T.”Caffeic acid phenethyl ester induces apoptosis by inhibition of NFkappaB and activation of Fas in human breast cancer MCF-7 cells.” J Biol Chem 279.7 (2004):6017-26.Print.

Wu, J, Omene, C, Karkoszka, J, Bosland, M, Eckard,J, Klein, CB and Frenkel, K. “Caffeic acid phenethyl ester (CAPE), derived from a honeybee product propolis, exhibits a diversity of anti-tumor effects in pre-clinical models of human breast cancer.”Cancer Lett 308.1 (2011):43-53.Print.

Yildiz Oguz Galip, Soyuer Serdar, Saraymen Saraymen and Eroglu Celalettin. “Protective effects of caffeic acid phenethyl ester on radiation induced lung injury in rats”.Clin Invest Med 31.5 (2008): E242-E247.Print.

How to Cite This?

Choose the style


NerdyRoo. (2022, May 15). Caffeic Acid Phenethyl Ester Effect on Lung Cancer, Breast Cancer, Cervical Cancer. Retrieved from

Work Cited

"Caffeic Acid Phenethyl Ester Effect on Lung Cancer, Breast Cancer, Cervical Cancer." NerdyRoo, 15 May 2022,

1. NerdyRoo. "Caffeic Acid Phenethyl Ester Effect on Lung Cancer, Breast Cancer, Cervical Cancer." May 15, 2022.


NerdyRoo. "Caffeic Acid Phenethyl Ester Effect on Lung Cancer, Breast Cancer, Cervical Cancer." May 15, 2022.


NerdyRoo. 2022. "Caffeic Acid Phenethyl Ester Effect on Lung Cancer, Breast Cancer, Cervical Cancer." May 15, 2022.


NerdyRoo. (2022) 'Caffeic Acid Phenethyl Ester Effect on Lung Cancer, Breast Cancer, Cervical Cancer'. 15 May.

Copy this

One of the best students granted us this essay, so that we share it with you. If the paper can be helpful for your studies, feel free to use it but don’t forget to cite it correctly.

Are you the author of this work? Did you change your mind and wish it to be deleted from NerdyRoo? Contact us here.