Berberine enhances chemosensitivity to irinotecan in colon cancer via inhibition of NF‑κB

Yu,Meiling; Tong,Xuhui; Qi,Benquan; Qu,Hongdang; Dong,Shuying; Yu,Binbin; Zhang,Naiju; Tang,Nan; Wang,Lingzhi; Zhang,Cuiling

doi:10.3892/mmr.2013.1762

Berberine enhances chemosensitivity to irinotecan in colon cancer via inhibition of NF‑κB

Authors:
- Meiling Yu
- Xuhui Tong
- Benquan Qi
- Hongdang Qu
- Shuying Dong
- Binbin Yu
- Naiju Zhang
- Nan Tang
- Lingzhi Wang
- Cuiling Zhang
View Affiliations

Affiliations: Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical College, Anhui, Bengbu 233004, P.R. China, Faculty of Pharmacy, Bengbu Medical College, Anhui, Bengbu 233030, P.R. China, Department of Pharmacy, Guangdong Medical College, Dongguan, Guangdong 523808, P.R. China, Department of Anaesthesia, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, P.R. China
Published online on: October 29, 2013 https://doi.org/10.3892/mmr.2013.1762
Pages: 249-254

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Previous studies have shown that irinotecan (CPT‑11) impairs chemotherapy‑induced apoptosis by activating nuclear factor‑κB (NF‑κB) and a number of strategies have been employed to augment chemosensitivity through the suppression of NF‑κB activation. Berberine, a botanical alkaloid, was reported to enhance chemosensitivity to 5‑fluorouracil and doxorubicin by suppressing NF‑κB activation. In the present study, the effect of berberine on CPT‑11‑induced apoptosis was investigated through the inhibition of NF‑κB. Inhibition of NF‑κB activation by p65 small interfering RNA was shown to potentiate apoptosis induced by CPT‑11. Berberine suppressed CPT‑11‑induced NF‑κB activation in a dose‑dependent manner and enhanced chemosensitivity to CPT‑11 by downregulating NF‑κB activation of antiapoptotic genes, c‑IAP1, c‑IAP2, survivin and Bcl‑xL. The current observations indicate that berberine inhibits NF‑κB activation and may be used to enhance CPT‑11‑induced apoptosis in colon cancer.

View Figures

View References

1	Sarkar FH and Li Y: Harnessing the fruits of nature for the development of multi-targeted cancer therapeutics. Cancer Treat Rev. 35:597–607. 2009. View Article : Google Scholar : PubMed/NCBI
2	Li F and Sethi G: Targeting transcription factor NF-kappaB to overcome chemoresistance and radioresistance in cancer therapy. Biochim Biophys Acta. 1805:167–180. 2010.PubMed/NCBI
3	Van Antwerp DJ, Martin SJ, Kafri T, Green DR and Verma IM: Suppression of TNF-alpha-induced apoptosis by NF-kappaB. Science. 274:787–789. 1996.PubMed/NCBI
4	Cusack JC Jr, Liu R and Baldwin AS Jr: Inducible chemoresistance to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (CPT-11) in colorectal cancer cells and a xenograft model is overcome by inhibition of nuclear factor-kappaB activation. Cancer Res. 60:2323–2330. 2000.PubMed/NCBI
5	Baldwin AS Jr: Series introduction: the transcription factor NF-kappaB and human disease. J Clin Investig. 107:3–6. 2001. View Article : Google Scholar : PubMed/NCBI
6	Wang CY, Mayo MW, Korneluk RG, Goeddel DV and Baldwin AS Jr: NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science. 281:1680–1683. 1998. View Article : Google Scholar : PubMed/NCBI
7	Xu Y and Villalona-Calero MA: Irinotecan: mechanism of tumor resistance and novel strategies for modulating its activity. Ann Oncol. 13:1841–1851. 2002. View Article : Google Scholar : PubMed/NCBI
8	Wasserman E, Sutherland W and Cvitkovic E: Irinotecan plus oxaliplatin: a promising combination for advanced colorectal cancer. Clin Colorectal Cancer. 1:149–153. 2001. View Article : Google Scholar : PubMed/NCBI
9	Stahel RA and Zangemeister-Wittke U: Antisense oligonucleotides for cancer therapy-an overview. Lung Cancer. 41(Suppl 1): S81–S88. 2003. View Article : Google Scholar : PubMed/NCBI
10	Shah SA, Potter MW, McDade TP, Ricciardi R, Perugini RA, Elliott PJ, Adams J and Callery MP: 26S proteasome inhibition induces apoptosis and limits growth of human pancreatic cancer. J Cell Biochem. 82:110–122. 2001. View Article : Google Scholar : PubMed/NCBI
11	Cusack JC Jr, Liu R, Houston M, Abendroth K, Elliott PJ, Adams J and Baldwin AS Jr: Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. Cancer Res. 61:3535–3540. 2001.PubMed/NCBI
12	Guo J, Verma UN, Gaynor RB, Frenkel EP and Becerra CR: Enhanced chemosensitivity to irinotecan by RNA interference-mediated down-regulation of the nuclear factor-kappaB p65 subunit. Clin Cancer Res. 10:3333–3341. 2004. View Article : Google Scholar
13	Lagdec P, Griessinger E, Nawrot MP, Fenouille N, Colosetti P, Imbert V, Mari M, Hofman P, Czerucka D, Rousseau D, et al: Pharmacological targeting of NF-kappaB potentiates the effect of the topoisomerase inhibitor CPT-11 on colon cancer cells. Br J Cancer. 98:335–344. 2008. View Article : Google Scholar : PubMed/NCBI
14	Liu S, Fang Y, Shen H, Xu W and Li H: Berberine sensitizes ovarian cancer cells to cisplatin through miR-21/PDCD4 axis. Acta Biochim Biophys Sin (Shanghai). 45:756–762. 2013. View Article : Google Scholar : PubMed/NCBI
15	Pandey MK, Sung B, Kunnumakkara AB, Sethi G, Chaturvedi MM and Aggarwal BB: Berberine modifies cysteine 179 of IkappaBalpha kinase, suppresses nuclear factor-kappaB-regulated antiapoptotic gene products, and potentiates apoptosis. Cancer Res. 68:5370–5379. 2008. View Article : Google Scholar
16	Papazisis KT, Geromichalos GD, Dimitriadis KA and Kortsaris AH: Optimization of the sulforhodamine B colorimetric assay. J Immumol Methods. 208:151–158. 1997. View Article : Google Scholar : PubMed/NCBI
17	Hussain AR, Ahmed SO, Ahmed M, Khan OS, Al Abdulmohsen S, Platanias LC, Al-Kuraya KS and Uddin S: Cross-Talk between NF-κB and the PI3-Kinase/AKT pathway can be targeted in primary effusion lymphoma (PEL) cell lines for efficient apoptosis. PLoS One. 7:e399452012.
18	Hussain AR, Ahmed M, Al-Jomah NA, Khan AS, Manogaran P, Sultana M, Abubaker J, Platanias LC, Al-Kuraya KS and Uddin S: Curcumin suppresses constitutive activation of nuclear factor-kappa B and requires functional Bax to induce apoptosis in Burkitt's lymphoma cell lines. Mol Cancer Ther. 7:3318–3329. 2008. View Article : Google Scholar : PubMed/NCBI
19	Wang Q, Zhang J, Liu L, Sharma S and Dong Q: Quercetin potentiates doxorubicin mediated antitumor effects against liver cancer through p53/Bcl-xl. PLoS One. 7:e517642012. View Article : Google Scholar : PubMed/NCBI
20	Zou Z, Xie L, Wei J, Yu L, Qian X, Chen J, Wang T and Liu B: Synergistic anti-proliferative effects of gambogic acid with docetaxel in gastrointestinal cancer cell lines. BMC Complement Altern Med. 12:582012. View Article : Google Scholar : PubMed/NCBI
21	Kawano Y, Nagata M, Kohno T, Ichimiya A, Iwakiri T, Okumura M and Arimori K: Caffeine increases the antitumor effect of Cisplatin in human hepatocellular carcinoma cells. Biol Pharm Bull. 35:400–407. 2012. View Article : Google Scholar : PubMed/NCBI
22	Pacifico F and Leonardi A: Role of NF-kappaB in thyroid cancer. Mol Cell Endocrinol. 321:29–35. 2010. View Article : Google Scholar : PubMed/NCBI
23	Baud V and Karin M: Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov. 8:33–40. 2009. View Article : Google Scholar : PubMed/NCBI
24	Kuoharczak J, Simmons MJ, Fan Y and Gélinas C: To be, or not to be: NF-kappaB is the answer - role of Rel/NF-kappaB in the regulation of apoptosis. Oncogene. 22:8961–8982. 2003. View Article : Google Scholar : PubMed/NCBI