A NATURAL PRODUCT DECURSIN ENHANCES THE RADIOSENSITIZATION OF IONIZING RADIATION AGAINST DMBA-INDUCED TUMOR
Objective: Radiation therapy has gained significant attention for the treatment and prevention of solid and malignant human tumors. However, after periodical exposures, radiation therapy losses its efficacy against cancer cells displaying radio-resistant phenotypes. Therefore, decursin might improve the efficiency of radiotherapy against a variety of human cancers.
Methods: The chemopreventive efficacy of decursin was evaluated against B16F10 cancer cell lines and DMBA/croton oil-induced skin carcinogenesis in BALB/c mice. Decursin was administered intraperitoneal at the dose of 20 mg/kg/day for 8 weeks following exposure to 5 Gy of ionizing radiation (IR) after 1 month of DMBA application. Western blot was performed for underlying mechanism of radioresistance.
Results: Decursin suppressed the proliferation and viability of melanoma cancer cell lines in a concentration- and time-dependent manner. The in vivo data collected from mice model revealed that decursin reduced the precancerous skin lesions and the incidence of tumor bearing in radiation-exposed mice. Decursin also enhanced the effect of IR by downregulation of Akt/NFκB pathway through activation of IκBα.
Conclusion: Our results suggest that the activation of Akt/NFκB establishes a pro-survival response to radiation that may account for the development of radioresistance. Decursin blocks the abnormal expression of these proteins and potentiates the radiotherapeutic effect.
2. Shehzad A, Park JW, Lee J, Lee YS. Curcumin induces radiosensitivity of in vitro and in vivo cancer models by modulating pre-mRNA processing factor 4 (Prp4). Chem Biol Interact 2013;206:394-402.
3. Chang DT, Amdur RJ, Morris CG, Mendenhall WM. Adjuvant radiotherapy for cutaneous melanoma: Comparing hypofractionation to conventional fractionation. Int J Radiat Oncol Biol Phys 2006;66:1051-5.
4. Camphausen K, Tofilon PJ. Combining radiation and molecular targeting in cancer therapy. Cancer Biol Ther 2004;3:247-50.
5. Al-Suhaimi EA. Curcumin induces apoptosis of 3T3-L1 adipocytes and affects molecular signals of adiponectin, AMPK and PKA. An Real Acad Farm 2104;80:720-34.
6. Chang L, Graham PH, Hao J, Ni J, Bucci J, Cozzi PJ, et al. Acquisition of epithelial-mesenchymal transition and cancer stem cell phenotypes is associated with activation of the PI3K/Akt/mTOR pathway in prostate cancer radioresistance. Cell Death Dis 2013;4:e875.
7. Nakanishi C, Toi M. Nuclear factor-kappaB inhibitors as sensitizers to anticancer drugs. Nat Rev Cancer 2005;5:297-309.
8. Kim BS, Seo H, Kim HJ, Bae SM, Son HN, Lee YJ, et al. Decursin from Angelica gigas nakai inhibits B16F10 melanoma growth through induction of apoptosis. J Med Food 2015;18:1121-7.
9. Kim JH, Jeong JH, Jeon ST, Kim H, Ock J, Suk K, et al. Decursin inhibits induction of inflammatory mediators by blocking nuclear factor-kappaB activation in macrophages. Mol Pharmacol 2006;69:1783-90.
10. Lee SH, Lee JH, Kim EJ, Kim WJ, Suk K, Kim JH, et al. A novel derivative of decursin, CSL-32, blocks migration and production of inflammatory mediators and modulates PI3K and NF-?B activities in HT1080 cells. Cell Biol Int 2012;36:683-8.
11. Shehzad A, Parveen S, Qureshi M, Subhan F, Lee YS. Decursin and decursinol angelate: Molecular mechanism and therapeutic potential in inflammatory diseases. Inflamm Res 2018;67:209-18.
12. Munshi A, Kurland JF, Nishikawa T, Chiao PJ, Andreeff M, Meyn RE, et al. Inhibition of constitutively activated nuclear factor-kappaB radiosensitizes human melanoma cells. Mol Cancer Ther 2004;3:985-92.
13. Al-Suhaimi E. Molecular mechanisms of leptin and pro-apoptotic signals induced by menadione in hepG2 cells. Saudi J Biol Sci 2014;21:582-8.
14. Schön M, Wienrich BG, Kneitz S, Sennefelder H, Amschler K, Vöhringer V, et al. KINK-1, a novel small-molecule inhibitor of IKKbeta, and the susceptibility of melanoma cells to antitumoral treatment. J Natl Cancer Inst 2008;100:862-75.
15. Yu CC, Hung SK, Lin HY, Chiou WY, Lee MS, Liao HF, et al. Targeting the PI3K/AKT/mTOR signaling pathway as an effectively radiosensitizing strategy for treating human oral squamous cell carcinoma in vitro and in vivo. Oncotarget 2017;8:68641-53.
16. Al Suhaimi EA. Effect of Corriandrum sativum, a common herbal medicine on endocrine and reproductive organ structure and function. Internet J Altern Med 2008;7:1540-2584.
17. Stahl JM, Sharma A, Cheung M, Zimmerman M, Cheng JQ, Bosenberg MW, et al. Deregulated akt3 activity promotes development of malignant melanoma. Cancer Res 2004;64:7002-10.
18. AL-Suhaimi EA, Fadwa M, Ravinayagam V, Mohammad H. Serum adipocytokines, metabolic and immunological correlations in Type 1 diabetes mellitus (T1DM) children. Open Endocrinol J 2012;6:110-6.
19. Dhawan P, Singh AB, Ellis DL, Richmond A. Constitutive activation of akt/protein kinase B in melanoma leads to up-regulation of nuclear factor-kappaB and tumor progression. Cancer Res 2002;62:7335-42.
20. Al-Suhaimi EA, Akbar A. Relationship of leptin hormone with insulin and glucose in Arabian camel (Camelus dromedarius). J Camel Pract Res 2009;16:201-7.
21. Al-Suwaigh EA, Al-Suhaimi EA. Comparative study on some biochemical constituents of plasma in male camels and goats. J Camel Pract Res 2014;12:141-3.
This work is licensed under a Creative Commons Attribution 4.0 International License.