CC BY-NC-ND 4.0 · Journal of Health and Allied Sciences NU 2021; 11(02): 080-086
DOI: 10.1055/s-0040-1722808
Original Article

Effect of Piperine in Combination with Gamma Radiation on A549 Cells

Koniyan Shaheer
1   Molecular Biology Division, Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, India
M. Divya Lakshmanan
1   Molecular Biology Division, Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, India
› Author Affiliations


Background Lung cancer is a major constrain that increases mortality globally. Radiotherapy is one of the treatment modalities against lung cancer. A high dose of targeted radiation is required to achieve the treatment efficacy of cell killing. After radiotherapy, eventual tumor progression and therapy resistance are still a consequence of patient who undertakes nonsurgical radiation therapy. Piperine, a plant alkaloid, has been known to enhance the action of the anticancer drugs in various drug-resistant cancer cells. The aim of the current in vitro study was to study the effect of piperine on radiosensitizing property against A549 cells.

Methods In vitro radiosensitizing activity of piperine was elucidated on A549 cells using MTT (3-(4, 5-dimethylthiazol-2-yl)-25-diphenyltetrazolium bromide) assay. CompuSyn analysis was used to compute the combination index values to analyze the combinatory effect of piperine and radiation

Results and Conclusion We observed that piperine increased tumor cell killing in combination with the γ-radiation in vitro. However, further studies are warranted to understand the molecular mechanism of the radiosensitizing action of piperine.

Publication History

Article published online:
10 February 2021

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  • References

  • 1 Wang S, Zimmermann S, Parikh K, Mansfield AS, Adjei AA. Current diagnosis and management of small-cell lung cancer. Mayo Clin Proc 2019; 94 (08) 1599-1622
  • 2 Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68 (06) 394-424
  • 3 Spratt DE, Wu AJ, Adeseye V. et al. Recurrence patterns and second primary lung cancers after stereotactic body radiation therapy for early-stage non-small-cell lung cancer: implications for surveillance. Clin Lung Cancer 2016; 17 (03) 177-183.e2, e172
  • 4 Zhao Y, Wang L, Huang Q. et al. Radiosensitization of non-small cell lung cancer cells by inhibition of TGF-β1 signaling with SB431542 is dependent on p53 status. Oncol Res 2016; 24 (01) 1-7
  • 5 Gupta S, Koru-Sengul T, Arnold SM, Devi GR, Mohiuddin M, Ahmed MM. Low-dose fractionated radiation potentiates the effects of cisplatin independent of the hyper-radiation sensitivity in human lung cancer cells. Mol Cancer Ther 2011; 10 (02) 292-302
  • 6 Kuo WT, Tsai YC, Wu HC. et al. Radiosensitization of non-small cell lung cancer by kaempferol. Oncol Rep 2015; 34 (05) 2351-2356
  • 7 Morgan MA, Parsels LA, Maybaum J, Lawrence TS. Improving the efficacy of chemoradiation with targeted agents. Cancer Discov 2014; 4 (03) 280-291
  • 8 Bose S, Banerjee S, Mondal A. et al. Targeting the JAK/STAT signaling pathway using phytocompounds for cancer prevention and therapy. Cells 2020; 9 (06) E1451
  • 9 Iqbal J, Abbasi BA, Batool R. et al. Potential phytocompounds for developing breast cancer therapeutics: nature’s healing touch. Eur J Pharmacol 2018; 827: 125-148
  • 10 Pistollato F, Calderón Iglesias R, Ruiz R. et al. The use of natural compounds for the targeting and chemoprevention of ovarian cancer. Cancer Lett 2017; 411: 191-200
  • 11 Ho ST, Tung YT, Kuo YH, Lin CC, Wu JH. Ferruginol inhibits non-small cell lung cancer growth by inducing caspase-associated apoptosis. Integr Cancer Ther 2015; 14 (01) 86-97
  • 12 Szejk M, Kołodziejczyk-Czepas J, Żbikowska HM. Radioprotectors in radiotherapy - advances in the potential application of phytochemicals. Postepy Hig Med Dosw 2016; 70 (00) 722-734
  • 13 Nicholson DW, Ali A, Thornberry NA. et al. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 1995; 376 (6535) 37-43
  • 14 Cao HY, Ding RL, Li M. et al. Danshensu, a major water-soluble component of Salvia miltiorrhiza, enhances the radioresponse for Lewis lung carcinoma xenografts in mice. Oncol Lett 2017; 13 (02) 605-612
  • 15 Javvadi P, Segan AT, Tuttle SW, Koumenis C. The chemopreventive agent curcumin is a potent radiosensitizer of human cervical tumor cells via increased reactive oxygen species production and overactivation of the mitogen-activated protein kinase pathway. Mol Pharmacol 2008; 73 (05) 1491-1501
  • 16 Lagerweij T, Hiddingh L, Biesmans D. et al. A chemical screen for medulloblastoma identifies quercetin as a putative radiosensitizer. Oncotarget 2016; 7 (24) 35776-35788
  • 17 Ortiz T, Lopez S, Burguillos MA, Edreira A, Piñero J. Radiosensitizer effect of wortmannin in radioresistant bladder tumoral cell lines. Int J Oncol 2004; 24 (01) 169-175
  • 18 Tang Q, Ma J, Sun J. et al. Genistein and AG1024 synergistically increase the radiosensitivity of prostate cancer cells. Oncol Rep 2018; 40 (02) 579-588
  • 19 Khan M, Maryam A, Mehmood T, Zhang Y, Ma T. Enhancing activity of anticancer drugs in multidrug resistant tumors by modulating P-glycoprotein through dietary nutraceuticals. Asian Pac J Cancer Prev 2015; 16 (16) 6831-6839
  • 20 Li H, Krstin S, Wang S, Wink M. Capsaicin and piperine can overcome multidrug resistance in cancer cells to doxorubicin. Molecules 2018; 23 (03) E557
  • 21 Manayi A, Nabavi SM, Setzer WN, Jafari S. Piperine as a potential anti-cancer agent: a review on preclinical studies. Curr Med Chem 2018; 25 (37) 4918-4928
  • 22 Syed SB, Arya H, Fu IH. et al. Targeting P-glycoprotein: Investigation of piperine analogs for overcoming drug resistance in cancer. Sci Rep 2017; 7 (01) 7972
  • 23 Bolat ZB, Islek Z, Demir BN, Yilmaz EN, Sahin F, Ucisik MH. Curcumin- and piperine-loaded emulsomes as combinational treatment approach enhance the anticancer activity of curcumin on HCT116 colorectal cancer model. Front Bioeng Biotechnol 2020; 8: 50
  • 24 Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res 2010; 70 (02) 440-446
  • 25 Tolosa L, Donato MT, Gómez-Lechón MJ. General cytotoxicity assessment by means of the MTT assay. Methods Mol Biol 2015; 1250: 333-348
  • 26 Shaheer K, Somashekarappa HM, Lakshmanan MD. Piperine sensitizes radiation-resistant cancer cells towards radiation and promotes intrinsic pathway of apoptosis. J Food Sci 2020; 85 (11) 4070-4079
  • 27 Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984; 22: 27-55
  • 28 Bang JS, Oh DH, Choi HM. et al. Anti-inflammatory and antiarthritic effects of piperine in human interleukin 1beta-stimulated fibroblast-like synoviocytes and in rat arthritis models. Arthritis Res Ther 2009; 11 (02) R49
  • 29 Stojanović-Radić ZP, Dimitrijević M, Aleksić A. et al. Piperine-a major principle of black pepper: a review of its bioactivity and studies. Appl Sci (Basel) 2019; (09) 4270
  • 30 Do MT, Kim HG, Choi JH. et al. Antitumor efficacy of piperine in the treatment of human HER2-overexpressing breast cancer cells. Food Chem 2013; 141 (03) 2591-2599
  • 31 Yaffe PB, Power MR Coombs, Doucette CD, Walsh M, Hoskin DW. Piperine, an alkaloid from black pepper, inhibits growth of human colon cancer cells via G1 arrest and apoptosis triggered by endoplasmic reticulum stress. Mol Carcinog 2015; 54 (10) 1070-1085
  • 32 Jafri A, Siddiqui S, Rais J. et al. Induction of apoptosis by piperine in human cervical adenocarcinoma via ROS mediated mitochondrial pathway and caspase-3 activation. EXCLI J 2019; 18: 154-164
  • 33 Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D’Orazi G. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY) 2016; 8 (04) 603-619
  • 34 Huang RX, Zhou PK. DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer. Signal Transduct Target Ther 2020; 5 (01) 60
  • 35 Ozpiskin OM, Zhang L, Li JJ. Immune targets in the tumor microenvironment treated by radiotherapy. Theranostics 2019; 9 (05) 1215-1231
  • 36 Carrano AV. Chromosome aberrations and radiation-induced cell death. II. Predicted and observed cell survival. Mutat Res 1973; 17 (03) 355-366
  • 37 Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 2006; 58 (03) 621-681
  • 38 Chou TC. The mass-action law based algorithms for quantitative econo-green bio-research. Integr Biol 2011; 3 (05) 548-559
  • 39 Chou TC. Frequently asked questions in drug combinations and the mass-action law-based answers. Synergy. 2014; (01) 3-21
  • 40 Fofaria NM, Kim SH, Srivastava SK. Piperine causes G1 phase cell cycle arrest and apoptosis in melanoma cells through checkpoint kinase-1 activation. PLoS One 2014; 9 (05) e94298