Molecular Biology Reports

, Volume 45, Issue 5, pp 1219–1225 | Cite as

Vicenin-2: a potential radiosensitizer of non-small cell lung cancer cells

  • Taranga Jyoti Baruah
  • R. N. Sharan
  • Lakhan KmaEmail author
Original Article


Non-small cell lung cancer (NSCLC) is a major form of cancer and is resistant to chemo- and radio-therapy. Vicenin-2 (VCN-2) is a flavonoid obtained from Ocimum sanctum L. and it has been reported to have radioprotective and anti-cancer properties. This study was conducted to check for the radiosensitizing potential of VCN-2 in the NSCLC cell line, NCI-H23. NCI-H23 cells were exposed to VCN-2 singularly, and to X-rays with and without prior VCN-2 treatment. Cytotoxicity assay, cell proliferation assay, caspase-3 activity assay, DNA fragmentation assay and Western blotting for Rad50, MMP-2 and p21 were performed to investigate the radiosensitizing properties of VCN-2. Fibroblast survival assay was performed using HEK293T cells to check for any adverse effects of VCN-2 on normal fibroblast cell line. VCN-2 singularly and in combination with radiation reduced the surviving cancer cells, increased caspase-3 activity, increased DNA fragmentation, increased the levels of Rad50 and lowered levels of MMP-2 and p21 proteins while being non-toxic and radioprotective to the fibroblast cells. VCN-2 showed a potent radiosensitizing property while also showing a chemotherapeutic property against NSCLC cell line NCI-H23.


Vicenin-2 Radiosensitization Caspase-3 Rad50 MMP-2 P21 



This work was supported by funds provided by Department of Science and Technology-Science and Engineering Research Board, New Delhi, India to Dr. L. Kma (SERB/F/3862/2014-15) and grant from University Grants Commission, New Delhi, India under Departmental Research Support-II & Departmental Research Support-III program to the Department of Biochemistry, NEHU, Shillong, India.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.


  1. 1.
    Wong MCS, Lao XQ, Ho KF et al (2017) Incidence and mortality of lung cancer: global trends and association with socioeconomic status. Sci Rep 7(1):14300CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Raghavan P, Tumati V, Yu L et al (2012) AZD5438, an inhibitor of Cdk1, 2, and 9, enhances the radiosensitivity of non-small cell lung carcinoma cells. Int J Radiat Oncol Biol Phys 84:e507–e514CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Kim JS, Amorino GP, Pyo H et al (2001) The novel taxane analogs, BMS-184476 and BMS-188797, potentiate the effects of radiation therapy in vitro and in vivo against human lung cancer cells. Int J Radiat Oncol Biol Phys 51:e525–e534CrossRefGoogle Scholar
  4. 4.
    Palayoor ST, Bump EA, Calderwood SK et al (1998) Combined antitumor effect of radiation and ibuprofen in human prostate carcinoma cells. Clin Cancer Res 4:763–771PubMedGoogle Scholar
  5. 5.
    Dicker AP, Williams TL, Grant DS (2001) Targeting angiogenic processes by combination rofecoxib and ionizing radiation. Am J Clin Oncol 24:438–442CrossRefPubMedGoogle Scholar
  6. 6.
    Kim KY, Seol JY, Jeon GA et al (2003) The combined treatment of aspirin and radiation induces apoptosis by the regulation of bcl-2 and caspase-3 in human cervical cancer cells. Cancer Lett 189:157–166CrossRefPubMedGoogle Scholar
  7. 7.
    Zhu AX, Willett CG (2003) Chemotherapeutic and biologic agents as radiosensitizers in rectal cancer. Semin Radiat Oncol 13:454–468CrossRefPubMedGoogle Scholar
  8. 8.
    Jones PD, de Lorimier LP, Kitchell BE et al (2003) Gemcitabine as a radiosensitizer for nonresectable feline oral squamous cell carcinoma. J Am Anim Hosp Assoc 39:463–467CrossRefPubMedGoogle Scholar
  9. 9.
    Cho HJ, Ahn KC, Choi JY et al (2015) Luteolin acts as a radiosensitizer in non-small cell lung cancer cells by enhancing apoptotic cell death through activation of a p38/ROS/caspase cascade. Int J Oncol 46:1149–1158CrossRefPubMedGoogle Scholar
  10. 10.
    Oleinick NL, Biswas T, Patel R et al (2016) Radiosensitization of non-small-cell lung cancer cells and xenografts by the interactive effects of pemetrexed and methoxyamine. Radiother Oncol 121:335–341CrossRefPubMedGoogle Scholar
  11. 11.
    Fennel DA (2005) Caspase regulation in non-small cell lung cancer and its potential for therapeutic exploitation. Clin Cancer Res 11:2097–2105CrossRefGoogle Scholar
  12. 12.
    Tarumi W, Suzuki N, Takahashi N et al (2009) Ovarian toxicity of paclitaxel and effect on fertility in the rat. J Obstet Gynaecol Res 35:414–420CrossRefPubMedGoogle Scholar
  13. 13.
    Kuo WT, Tsai YC, Wu HU et al (2015) Radiosensitization of non-small cell lung cancer by kaempferol. Oncol Rep 34:2351–2356CrossRefPubMedGoogle Scholar
  14. 14.
    Ramachandran RK, Sørensen MD, Aaberg-Jessen C et al (2017) Expression and prognostic impact of matrix metalloproteinase-2 (MMP-2) in astrocytomas. PLoS ONE 12:e0172234CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Leroi N, Lallemand F, Coucke P et al (2016) Impacts of ionizing radiation on the different compartments of the tumor microenviroment. Front Pharmacol 7:78CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Abbas T, Dutta A (2009) p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer 9:400–414CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Caputi M, Esposito A, Baldi A et al (1998) p21waf1/cip1mda–6 expression in non-small cell lung cancer: relationship to survival. Am J Respir Cell Mol Biol 18:213–217CrossRefPubMedGoogle Scholar
  18. 18.
    Xei D, Lan L, Huang K et al (2014) Association of p53/p21 expression and cigarette smoking with tumor progression and poor prognosis in non-small cell lung cancer patients. Oncol Rep 32:2517–2526CrossRefGoogle Scholar
  19. 19.
    Weiss RH (2003) p21Waf1/Cip1 as a therapeutic target in breast and other cancers. Cancer Cell 4:425–429CrossRefPubMedGoogle Scholar
  20. 20.
    Xie H, Li C, Dang Q et al (2016) Infiltrating mast cells increase prostate cancer chemotherapy and radiotherapy resistances via modulation of p38/p53/p21 and ATM signals. Oncotarget 7:1341–1353PubMedGoogle Scholar
  21. 21.
    Tran TQ, Lowman XH, Reid MA et al (2017) Tumor-associated mutant p53 promotes cancer cell survival upon glutamine deprivation through p21 induction. Oncogene 36:181–189CrossRefGoogle Scholar
  22. 22.
    Uma Devi P, Ganasoundari A, Rao BSS et al (1999) In vivo radioprotection by ocimum flavonoids: survival of mice. Radiat Res 151:74–78CrossRefPubMedGoogle Scholar
  23. 23.
    Uma Devi P, Ganasoundari A, Vrinda B et al (2000) Radiation protection by the ocimum flavonoids orientin and vicenin: mechanisms of action. Radiat Res 154:455–460CrossRefPubMedGoogle Scholar
  24. 24.
    Nayak V, Devi PU (2005) Protection of mouse bone marrow against radiation-induced chromosome damage and stem cell death by the ocimum flavonoids orientin and vicenin. Radiat Res 162:165–171CrossRefGoogle Scholar
  25. 25.
    Reshma K, Rao AV, Dinesh M et al (2008) Radioprotective effects of ocimum flavonoids on leukocyte oxidants and antioxidants in oral cancer. Indian J Clin Biochem 23:171–175CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Nagaprashantha LD, Vatsyayan R, Singhal J et al (2011) Anti-cancer effects of novel flavonoid vicenin-2 as a single agent and in synergistic combination with docetaxel in prostate cancer. Biochem Pharmacol 82:1100–1109CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Rahbar Saadat Y, Saeidi N, Vahed SZ et al (2015) An update to DNA ladder assay for apoptosis detection. Bioimpacts 5:25–28CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Choudhury Y, Sharan RN (2009) Altered p53 response and enchanced transgenerational transmission of carcinogenic risk upon exposure of mice to betel nut. Environ Toxicol Pharmacol 27:127–138CrossRefPubMedGoogle Scholar
  29. 29.
    Kma L, Sharan RN (2014) Dimethylnitrosamine-induced reduction in the level of poly-ADP-ribosylation of histone proteins of blood lymphocytes-a sensitive and reliable biomarker for early detection of cancer. Asian Pac J Cancer Prev 15:6429–6436CrossRefPubMedGoogle Scholar
  30. 30.
    Magesh V, Lee JC, Ahn KS et al (2009) Ocimum sanctum induces apoptosis in A549 lung cancer cells and suppresses the in vivo growth of Lewis lung carcinoma cells. Phytother Res 23:1385–1391CrossRefPubMedGoogle Scholar
  31. 31.
    Wätjen W, Michels G, Steffan B et al (2005) Low concentrations of flavonoids are protective in rat H4IIE cells whereas high concentrations cause DNA damage and apoptosis. J Nutr 135:525–531CrossRefPubMedGoogle Scholar
  32. 32.
    Sak K (2014) Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev 8:122–146CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Dey S, Spring PM, Arnold S et al (2003) Low-dose fractionated radiation potentiates the effects of paclitaxel in wild-type and mutant p53 head and neck tumor cell lines. Clin Cancer Res 9:1557–1565PubMedGoogle Scholar
  34. 34.
    Li F, Zhou K, Gao L et al (2016) Radiation induces the generation of cancer stem cells: a novel mechanism for cancer radioresistance. Oncol Lett 12:3059–3065CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Zhao X, Cui JW, Hu JH (2017) Effects of low-dose radiation on adaptive response in colon cancer stem cells. Clin Transl Oncol 19:907–914CrossRefPubMedGoogle Scholar
  36. 36.
    Cullen SP, Martin SJ (2009) Caspase activation pathways: some recent progress. Cell Death Differ 16:935–938CrossRefPubMedGoogle Scholar
  37. 37.
    Huang Q, Li F, Liu X et al (2011) Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nat Med 17:860–866CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Nagata S, Nagase H, Kawane K et al (2003) Degradation of chromosomal DNA during apoptosis. Cell Death Differ 10:108–116CrossRefPubMedGoogle Scholar
  39. 39.
    Yuste VJ, Bayascas JR, Llecha N et al (2001) The absence of oligonucleosomal DNA fragmentation during apoptosis of IMR-5 neuroblastoma cells: disappearance of the caspase-activated DNase. J Biol Chem 276:22323–22331CrossRefPubMedGoogle Scholar
  40. 40.
    Sikora E, Bielak-Zmijewska A, Magalska A et al (2006) Curcumin induces caspase-3-dependent apoptotic pathway but inhibits DNA fragmentation factor 40/caspase-activated DNase endonuclease in human Jurkat cells. Mol Cancer Ther 5:927–934CrossRefPubMedGoogle Scholar
  41. 41.
    Newman AC, Scholefield CL, Kemp AJ et al (2012) TBK1 kinase addiction in lung cancer cells is mediated via autophagy of Tax1bp1/Ndp52 and non-canonical Nf-kB signaling. PLoS ONE 7:e50672CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Nowsheen S, Yang ES (2012) The intersection between DNA damage response and cell death pathways. Exp Oncol 34:243–254PubMedPubMedCentralGoogle Scholar
  43. 43.
    Stracker TH, Petrini JH (2011) The MRE11 complex: starting from the ends. Nat Rev Mol Cell Biol 12:90–103CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Morales M, Theunissen JWF, Kim CFB et al (2005) The Rad50 S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor. Genes Dev 19:3043–3054CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Shin BA, Ahn KY, Kook H et al (2001) Overexpressed human RAD50 exhibits cell death in a p21(WAF1/CIP1)-dependent manner: its potential utility in local gene therapy of tumor. Cell Growth Differ 12:243–254PubMedGoogle Scholar
  46. 46.
    Khan MS, Halagowder D, Devaraj SN (2011) Methylated chrysin, a dimethoxy flavone, partially suppresses the development of liver preneoplastic lesions induced by N-nitrosodiethylamine in rats. Food Chem Toxicol 49:173–178CrossRefPubMedGoogle Scholar
  47. 47.
    Chetty C, Bhoopathi P, Rao JS et al (2009) Inhibition of matrix metalloproteinase-2 enhances radiosensitivity by abrogating radiation-induced FoxM1-mediated G2/M arrest in A549 lung cancer cells. Int J Cancer 124:2468–2477CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Dai ZJ, Wang BF, Lu WF et al (2013) Total flavonoids of Scutellaria barbata inhibit invasion of hepatocarcinoma via MMP/TIMP in vitro. Molecules 18:934–950CrossRefPubMedGoogle Scholar
  49. 49.
    Takahashi T, Carbone D, Takahashi T et al (1992) Wild-type but not mutant p53 suppresses the growth of human lung cancer cells bearing multiple genetic lesions. Cancer Res 52:2340–2343PubMedGoogle Scholar
  50. 50.
    Georgakilas AG, Martin OA, Bonner WM (2017) p21: a two-faced genome guardian. Trends Mol Med 23:310–319CrossRefPubMedGoogle Scholar
  51. 51.
    Chetty C, Bhoopathi P, Lakka SS et al (2007) MMP-2 siRNA induced Fas/CD95-mediated extrinsic II apoptotic pathway in the A549 lung adenocarcinoma cell line. Oncogene 26:7675–7683CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Sak A, Wurm R, Elo B et al (2003) Increased radiation-induced apoptosis and altered cell cycle progression of human lung cancer cell lines by antisense oligodeoxynucleotides targeting p53 and p21(WAF1/CIP1). Cancer Gene Ther 10:926–934CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Taranga Jyoti Baruah
    • 1
    • 2
  • R. N. Sharan
    • 2
  • Lakhan Kma
    • 1
    Email author
  1. 1.Cancer and Radiation Countermeasures Unit, Department of BiochemistryNorth-Eastern Hill UniversityShillongIndia
  2. 2.Radiation and Molecular Biology Unit, Department of BiochemistryNorth-Eastern Hill UniversityShillongIndia

Personalised recommendations