Capsaicin inhibits proliferation and induces apoptosis in human lung adenocarcinoma A549 cell line

Abstract

Capsaicin is the main component of many hot peppers, exerts anticancer effects on various cancer cells by inducing apoptotic pathways. In addition, the ineffectiveness of this apoptotic effect of capsaicin on healthy cells provides a wide-ranging use of capsaicin. In recent years, many studies have been carried out to determine the safety of capsaicin use in lung cancer, which is a common cancer type worldwide with high mortality rates. In the present study anticancer effects of capsaicin were studied on A549 human lung adenocarcinoma cell line. Also, citotoxicity of this compound was studied on L929 mouse embryonic fibroblast cell line. Various concentration of capsaicin (3.90625-500 μM) effectively decreased cell viability in A549 cell line in a dose-dependent manner. Also, this antiproliferative effect of capsaicin was selective compared to L929 cell line. On the other hand, apoptosis inducing effects of capsaicin were studied by Annexin V-FITC and Caspase 3 assays by using IC50 and IC50/2 concentrations on A549 cell by flow cytometric methods. Our results revealed that the anticancer effects induced by capsaicin on A549 cell line involved apoptosis by inducing Caspase 3 pathway.

Keywords

• Capsaicin
• A549
• apoptosis
• flow cytometry

References

1. 1. Wolff H, Saukkonen K, Anttila S, Karjalainen A, Vainio H, Ristimäki A. Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res. 1998;58(22):4997-5001. https://www.researchgate.net/publication/237264292
2. 2. Parashar P, Tripathi CB, Arya M, et al. A synergistic approach for management of lung carcinoma through folic acid functionalized co-therapy of capsaicin and gefitinib nanoparticles: Enhanced apoptosis and metalloproteinase-9 down-regulation. Phytomedicine. 2019;53:107-123. https://doi.org/10.1016/j. phymed.2018.09.013
3. 3. Han TH, Park MK, Nakamura H, Ban HS. Capsaicin inhibits HIF-1α accumulation through suppression of mitochondrial respiration in lung cancer cells. Biomed Pharmacother. 2022;146:112500. https://doi. org/10.1016/j.biopha.2021.112500
4. 4. Merritt JC, Richbart SD, Moles EG, et al. Anti-cancer activity of sustained release capsaicin formulations. Pharmacol Ther. 2022;238:108177. https://doi. org/10.1016/j.pharmthera.2022.108177
5. 5. Lewinska A, Jarosz P, Czech J, et al. Capsaicin-induced genotoxic stress does not promote apoptosis in A549 human lung and DU145 prostate cancer cells. Mutat Res Genet Toxicol Environ Mutagen. 2015;779:23-34. https:// doi.org/10.1016/j.mrgentox.2015.02.003
6. 6. Lee YH, Chen HY, Su LJ, Chueh PJ. Sirtuin 1 (SIRT1) Deacetylase Activity and NAD+/NADH Ratio Are Imperative for Capsaicin-Mediated Programmed Cell Death. J Agric Food Chem. 2015;63(33):7361-7370. https://doi.org/10.1021/acs.jafc.5b02876
7. 7. Pramanik KC, Srivastava SK. Apoptosis signal-regulating kinase 1-thioredoxin complex dissociation by capsaicin causes pancreatic tumor growth suppression by inducing apoptosis. Antioxid Redox Signal. 2012;17(10):1417- 1432. https://doi.org/10.1089/ars.2011.4369
8. 8. Cooper GM, Hausman RE. The cell: A molecular approach. Sunderland (MA): Sinauer Associates; 2013. p. 686-687.

9. 9. Liu XY, Wei DG, Li RS. Capsaicin induces ferroptosis of NSCLC by regulating SLC7A11/GPX4 signaling in vitro. Sci Rep. 2022;12(1):11996. https://doi.org/10.1038/ s41598-022-16372-3
10. 10. Lewinska A, Chochrek P, Smolag K, Rawska E, Wnuk M. Oxidant-based anticancer activity of a novel synthetic analogue of capsaicin, capsaicin epoxide. Redox Rep. 2015;20(3):116-125. https://doi. org/10.1179/1351000214Y.0000000113
11. 11. Tsou MF, Lu HF, Chen SC, et al. Involvement of Bax, Bcl-2, Ca2+ and caspase-3 in capsaicin-induced apoptosis of human leukemia HL-60 cells. Anticancer Res. 2006;26(3A):1965-1971.
12. 12. Lee YS, Nam DH, Kim JA. Induction of apoptosis by capsaicin in A172 human glioblastoma cells. Cancer Lett. 2000;161(1):121-130. https://doi.org/10.1016/S0304- 3835(00)00608-X
13. 13. Chang HC, Chen ST, Chien SY, Kuo SJ, Tsai HT, Chen DR. Capsaicin may induce breast cancer cell death through apoptosis-inducing factor involving mitochondrial dysfunction. Hum Exp Toxicol. 2011;30(10):1657-1665. https://doi.org/10.1177/0960327110396530
14. 14. Lin YT, Wang HC, Hsu YC, Cho CL, Yang MY, Chien CY. Capsaicin Induces Autophagy and Apoptosis in Human Nasopharyngeal Carcinoma Cells by Downregulating the PI3K/AKT/mTOR Pathway. Int J Mol Sci. 2017;18(7):1343. https://doi.org/10.3390/ijms18071343
15. 15. Chou CC, Wu YC, Wang YF, Chou MJ, Kuo SJ, Chen DR. Capsaicin-induced apoptosis in human breast cancer MCF-7 cells through caspase-independent pathway. Oncol Rep. 2009;21(3):665-671. https://doi.org/10.3892/ or_00000269
16. 16. Hickman JA, Potten CS, Merritt AJ, Fisher TC. Apoptosis and cancer chemotherapy. Philos Trans R Soc Lond B Biol Sci. 1994;345(1313):319-325. http://doi.org/10.1098/ rstb.1994.0112
17. 17. Mancini M, Nicholson DW, Roy S, et al. The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling. J Cell Biol. 1998;140(6):1485-1495. https://doi.org/10.1083/ jcb.140.6.148513. HC Chang, ST Chen, SY Chien, SJ Kuo1, HT Tsai ,and DR Chen, Capsaicin may induce breast cancer cell death through apoptosis-inducing factor involving mitochondrial dysfunction, Human and Experimental Toxicology 30(10), 2011,1657–1665.
18. 18. Çiftçi GA, Işcan A, Kutlu M. Escin reduces cell proliferation and induces apoptosis on glioma and lung adenocarcinoma cell lines. Cytotechnology. 2015;67(5):893-904. https://doi.org/10.1007/s10616-015- 9877-6
19. 19. Hansakul P, Aree K, Tanuchit S, Itharat A. Growth arrest and apoptosis via caspase activation of dioscoreanone in human non-small-cell lung cancer A549 cells. BMC Complement Altern Med. 2014;14:413. https://doi. org/10.1186/1472-6882-14-413
20. 20. Kim MY, Trudel LJ, Wogan GN. Apoptosis induced by capsaicin and resveratrol in colon carcinoma cells requires nitric oxide production and caspase activation. Anticancer Res. 2009;29(10):3733-3740.
21. 21. Liu T, Wang G, Tao H, et al. Capsaicin mediates caspases activation and induces apoptosis through P38 and JNK MAPK pathways in human renal carcinoma. BMC Cancer. 2016;16(1):790. https://doi.org/10.1186/s12885- 016-2831-y