Apoptotic and Anti-Metastatic Effect of Carvacrol in PANC-1 Human Pancreatic Cancer Cells



Apoptosis, Carvacrol, EMT, Metastasis, PANC-1 cells


Pancreatic cancer is known to have one of the highest mortality rates among other cancer. Monoterpenes are natural compounds obtained from essential oils of plants. Carvacrol is a monoterpene phenolic derived from essential oils of various aromatic plants. In this study, the effects of carvacrol on proliferation, apoptosis and metastasis of PANC-1 human pancreatic cancer cells were investigated. XTT assay was used to determine cell proliferation and viability. mRNA level expression levels of BAX, BCL2, CASP3, CASP7, CASP8, CASP9, CYCS, FADD, FAS and P53 were evaluated for determining the effect of carvacrol on apoptosis by qRT-PCR analysis. In addition, gene expressions of CDH1, CDH2, TIMP1, TIMP2, TIMP3, ZEB1 and ZEB2 were analyzed to evaluate its effect on metastasis. Carvacrol inhibited the PANC-1 pancreatic cancer cell proliferation in dose and time dependent manner. Carvacrol treatment induced apoptosis by changing the expressions of genes important in apoptosis. Moreover, it suppressed the metastasis by effecting CDH1, CDH2, TIMP2, TIMP3 and ZEB2 expressions. In conclusion, carvacrol showed apoptotic and anti-metastatic effects in PANC-1 human pancreatic cancer cells. It is thereby concluded that carvacrol may have a therapeutic potential in pancreatic cancer.


Ahmad, A., & Ansari, I. A. (2021). Carvacrol exhibits chemopreventive potential against cervical cancer cells via caspase-dependent apoptosis and abrogation of cell cycle progression. Anticancer Agents Med. Chem., 21(16), 2224-2235. https://doi.org/10.2174/1871520621999201230201258

American Cancer Society. (2022). Cancer Facts & Figures 2022, Atlanta: American Cancer Society.

Aubrey, B. J., Kelly, G. L., Janic, A., Herold, M. J., & Strasser, A. (2018). How does p53 induce apoptosis and how does this relate to p53 mediated tumour suppression? Cell Death Differ., 25(1), 104-113. https://doi.org/10.1038/cdd.2017.169

Baj, T., Biernasiuk, A., Wróbel, R., & Malm, A. (2020). Chemical composition and in vitro activity of Origanum vulgare L., Satureja hortensis L., Thymus serpyllum L. and Thymus vulgaris L. essential oils towards oral isolates of candida albicans and candida glabrata. Open Chem., 18(1), 108–118. https://doi.org/10.1515/chem-2020-0011

Ben Arfa, A., Combes, S., Preziosi-Belloy, L., Gontard, N., & Chalier, P. (2006). Antimicrobial activity of carvacrol related to its chemical structure. Lett. Appl. Microbiol., 43, 149–154. https://doi.org/10.1111/j.1472-765X.2006.01938.x

Bhakkiyalakshmi, E., Suganya, N., Sireesh, D., Krishnamurthi, K., Saravana Devi, S., Rajaguru, P., & Ramkumar, K. M. (2016). Carvacrol induces mitochondria-mediated apoptosis in HL-60 promyelocytic and Jurkat T lymphoma cells. Eur. J. Pharmacol., 772, 92-98. https://doi.org/10.1016/j.ejphar.2015.12.046

Can Baser, K., (2008). Biological and pharmacological activities of carvacrol and carvacrol bearing essential oils. Curr. Pharmaceut. Des., 14, 3106–3119. https://doi.org/10.2174/138161208786404227

Chen, W. L., Barszczyk, A., Turlova, E., Deurloo, M., Liu, B., Yang, B. B., Rutka, J. T., Feng Z. P., & Sun, H. S. (2015). Inhibition of TRPM7 by carvacrol suppresses glioblastoma cell proliferation, migration and invasion. Oncotarget. 6(18), 16321-16340. https://doi.org/10.18632/oncotarget.3872

Dai, W., Sun, C., Huang, S., & Zhou, Q. (2016). Carvacrol suppresses proliferation and invasion in human oral squamous cell carcinoma. Onco. Targets Ther., 9, 2297-2304. https://doi.org/10.2147/OTT.S98875

Elbe, H., Yigitturk, G., Cavusoglu, T., Baygar, T., Ozgul Onal, M., & Ozturk, F. (2020). Comparison of ultrastructural changes and the anticarcinogenic effects of thymol and carvacrol on ovarian cancer cells: which is more effective? Ultrastruct. Pathol., 44(2), 193-202. https://doi.org/10.1080/01913123.2020.1740366

Eroğlu-Güneş, C., Güçlü, E., Vural, H., & Kurar, E. (2021). Knockdown of lncRNA ZEB2NAT suppresses epithelial mesenchymal transition, metastasis and proliferation in breast cancer cells. Gene., 805, 145904. https://doi.org/10.1016/j.gene.2021.145904

Fan, K., Li, X., Cao, Y., Qi, H., Li, L., Zhang, Q., & Sun, H. (2015). Carvacrol inhibits proliferation and induces apoptosis in human colon cancer cells. Anti Cancer Drugs., 26, 813–823. https://doi.org/10.1097/CAD.0000000000000263

Gholijani, N., Gharagozloo, M., Kalantar, F., Ramezani, A., & Amirghofran, Z. (2015). Modulation of cytokine production and transcription factors activities in human Jurkat T cells by thymol and carvacrol. Adv. Pharm. Bull., 5(Suppl 1), 653-660. https://doi.org/10.15171/apb.2015.089

Guimarães, A. G., Oliveira, G. F., Melo, M. S., Cavalcanti, S. C. H., Antoniolli, A. R., Bonjardim, L. R., Silva, F. A., Santos, J. P. A., Rocha, R. F., Moreira, J. C. F., Araújo, A. A. S., Gelain, D.P., & Quintans-Júnior, L.J. (2010). Bioassay-guided evaluation of antioxidant and antinociceptive activities of carvacrol. Basic Clin. Pharmacol. Toxicol., 107, 949–957. https://doi.org/10.1111/j.1742-7843.2010.00609.x

Guimarães, A. G., Xavier, M. A., De Santana, M. T., Camargo, E. A., Santos, C. A., Brito, F. A., Barreto, E. O., Cavalcanti, S. C. H., Antoniolli, Â. R., Oliveira, R. C. M., & Quintans-Júnior, L.J. (2012). Carvacrol attenuates mechanical hypernociception and inflammatory response. Naunyn-Schmiedeberg’s Arch. Pharmacol., 385, 253–263. https://doi.org/10.1007/s00210-011-0715-x

Günes-Bayir, A., Kocyigit, A., & Güler, E. M. (2018a). In vitro effects of two major phenolic compounds from the family Lamiaceae plants on the human gastric carcinoma cells. Toxicol. Ind. Health., 34(8), 525-539. https://doi.org/10.1177/0748233718761698

Günes-Bayir, A., Kocyigit, A., Güler, E. M., Bilgin, M. G., Ergün, İ. S., & Dadak, A. (2018b). Effects of carvacrol on human fibroblast (WS-1) and gastric adenocarcinoma (AGS) cells in vitro and on Wistar rats in vivo. Mol. Cell. Biochem., 1–13. https://doi.org/10.1007/s11010-018-3329-5

Hay, E. D., & Zuk, A. (1995). Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am. J. Kidney Dis., 26(4), 678–690.

Heidarian, E., & Keloushadi, M. (2019). Antiproliferative and anti-invasion effects of carvacrol on PC3 human prostate cancer cells through reducing pstat3, pakt, and perk1/2 signaling proteins. Int. J. Prev. Med., 9(10), 156. https://doi.org/10.4103/ijpvm.IJPVM_292_17

Khan, F., Khan, I., Farooqui, A., & Ansari, I. A. (2017) Carvacrol induces reactive oxygen species (ROS)-mediated apoptosis along with cell cycle arrest at G0/G1 in human prostate cancer cells. Nutr. Cancer., 69(7), 1075-1087. https://doi.org/10.1080/01635581.2017.1359321

Khan, I., Bahuguna, A., Bhardwaj, M., Pal Khaket, T., & Kang, S. C. (2018a). Carvacrol nanoemulsion evokes cell cycle arrest, apoptosis induction and autophagy inhibition in doxorubicin resistant-A549 cell line. Artif. Cells Nanomed. Biotechnol., 46 (sup1), 664-675. https://doi.org/10.1080/21691401.2018.1434187

Khan, I., Bahuguna, A., Kumar, P., Bajpai, V. K., & Kang, S. C. (2018b) In vitro and in vivo antitumor potential of carvacrol nanoemulsion against human lung adenocarcinoma A549 cells via mitochondrial mediated apoptosis. Sci Rep., 8(1), 144. https://doi.org/10.1038/s41598-017-18644-9

Khan, F., Singh, V. K., Saeed, M., Kausar, M. A., & Ansari, I. A. (2019). Carvacrol induced program cell death and cell cycle arrest in androgen-independent human prostate cancer cells via inhibition of Notch signaling. Anticancer Agents Med. Chem., 19(13), 1588-1608. https://doi.org/10.2174/1871520619666190731152942

Koparal, A. T., & Zeytinoglu, M., (2003). Effects of carvacrol on a human non-small cell lung cancer (NSCLC) cell line, A549. Cytotechnology., 43, 149–154.

Kuehn, B.M. (2020). Looking to long-term survivors for improved pancreatic cancer treatment. JAMA., 324, 2242–2244.

Li, L., He, L., Wu, Y., & Zhang, Y. (2021). Carvacrol affects breast cancer cells through TRPM7 mediated cell cycle regulation. Life Sci., 266, 118894. https://doi.org/10.1016/j.lfs.2020.118894

Liang, Y., Yang, A. Y., Liu, M., Cheng, Y. J., Zang, S. B., Huang, J., Tang, Y. Y., & Huang, Z. P. (2022). Effect of carvacrol on the biological behavior of leukemia cells and its mechanism. Zhongguo Shi Yan Xue Ye Xue Za Zhi., 30(2), 393-399. https://doi.org/10.19746/j.cnki.issn.1009-2137.2022.02.012

Lim, W., Ham, J., Bazer, F. W., & Song, G. (2019). Carvacrol induces mitochondria-mediated apoptosis via disruption of calcium homeostasis in human choriocarcinoma cells. J. Cell Physiol., 234(2), 1803-1815. https://doi.org/10.1002/jcp.27054

Liu, H., Xu, X., Wu, R., Bi, L., Zhang, C., Chen, H., & Yang, Y. (2021). Antioral squamous cell carcinoma effects of carvacrol via inhibiting inflammation, proliferation, and migration related to Nrf2/Keap1 pathway. Biomed. Res. Int., 6616547. https://doi.org/10.1155/2021/6616547

Luo, Y., Wu, J. Y., Lu, M.H., Shi, Z., Na, N., & Di, J. M. (2016). Carvacrol alleviates prostate cancer cell proliferation, migration, and invasion through regulation of PI3K/Akt and MAPK signaling pathways. Oxid. Med. Cell Longev., 1469693. https://doi.org/10.1155/2016/1469693

Peinado, H., Olmeda, D., & Cano, A. (2007). Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat. Rev. Cancer., 7(6), 415–428.

Potočnjak, I., Gobin, I., & Domitrović, R. (2018). Carvacrol induces cytotoxicity in human cervical cancer cells but causes cisplatin resistance: Involvement of MEK-ERK activation. Phytother. Res., 32(6), 1090-1097. https://doi.org/10.1002/ptr.6048

Rejhová, A., Opattová, A., Čumová, A., Slíva, D., & Vodička, P. (2018). Natural compounds and combination therapy in colorectal cancer treatment. Eur. J. Med. Chem., 144, 582–594. https://doi.org/10.1016/j.ejmech.2017.12.039

Secme, M., Kaygusuz, O., Eroglu, C., Dodurga, Y., Colak, O. F., & Atmaca, P. (2018). Potential anticancer activity of the parasol mushroom, Macrolepiota procera (Agaricomycetes), against the A549 Human Lung Cancer Cell Line. Int. J. Med. Mushrooms., 20(11), 1075-1086. https://doi.org/10.1615/IntJMedMushrooms.2018028589

Souza, M. T. S., Teixeira, D. F., de Oliveira, J. P., Oliveira, A. S., Quintans-Júnior, L. J., Correa, C. B., & Camargo, E. A. (2017). Protective effect of carvacrol on acetic acid-induced colitis. Biomed. Pharmacother., 96, 313–319. https://doi.org/10.1016/j.biopha.2017.10.017

Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. Cancer J. Clin., 71, 209–249.

Yin, Q., Yan, F., Zu, X. Y., Wu, Y., Wu, X., Liao, M., Deng, S., Yin, L., & Zhuang, Y. (2012). Anti-proliferative and pro-apoptotic effect of carvacrol on human hepatocellular carcinoma cell line HepG-2. Cytotechnology., 64, 43–51. https://doi.org/10.1007/s10616-011-9389-y

Yin, X., Chen, H., Chen, S., & Zhang, S. (2022). Screening and validation of a carvacrol-targeting viability-regulating protein, SLC6A3, in liver hepatocellular carcinoma. Dis Markers., 2022, 3736104. https://doi.org/10.1155/2022/3736104

Zhang, S., He, L., Shang, J., Chen, L., Xu, Y., Chen, X., Li, X., Jiao, Q., Jin, S., Hu, X., & Liang, W. (2021). Carvacrol suppresses human osteosarcoma cells via the Wnt/β-Catenin signaling pathway. Anticancer Agents Med. Chem., 22(9), 1714-1722. https://doi.org/10.2174/1871520621666210901111932




How to Cite

Eroglu Gunes, C. ., Secme, M., Kurar, E., & Donmez, H. (2022). Apoptotic and Anti-Metastatic Effect of Carvacrol in PANC-1 Human Pancreatic Cancer Cells. Natural Products and Biotechnology, 2(1), 42–50. Retrieved from https://natprobiotech.com/index.php/natprobiotech/article/view/31



Research Article