Combination of Curcumin and Metformin Inhibits Cell Growth and Induces Apoptosis without Affecting the Cell Cycle in LNCaP Prostate Cancer Cell Line

被引:28
作者
Eslami, Seyed Sadegh [1 ]
Jafari, Davod [1 ]
Montazeri, Hamed [2 ]
Sadeghizadeh, Majid [3 ]
Tarighi, Parastoo [1 ]
机构
[1] Iran Univ Med Sci, Fac Allied Med, Dept Med Biotechnol, Tehran, Iran
[2] Iran Univ Med Sciences, Sch Pharm, Int Campus, Tehran, Iran
[3] Tarbiat Modares Univ, Fac Biol Sci, Dept Mol Genet, Tehran, Iran
来源
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL | 2021年 / 73卷 / 06期
关键词
NANO-ENCAPSULATED METFORMIN; HTERT GENE-EXPRESSION; BREAST-CANCER; IN-VITRO; BAX/BCL-2; RATIO; UP-REGULATION; PROLIFERATION; ACTIVATION; INDUCTION; THERAPY;
D O I
10.1080/01635581.2020.1783327
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Side effects and chemotherapy resistance, demand new therapeutics with minimal side effects. Here, we investigated the combined effect of curcumin and metformin on the LNCaP prostate cancer cell line. LNCaP cells were treated with curcumin, metformin, and their combination at different concentrations. Cell viability was assessed by MTT assay and expression ofBax, Bcl-2, mTOR, hTERT, PUMA, p53andp21genes was analyzed by real-time PCR. Apoptosis and cell cycle were assessed by flow cytometry. Our results revealed that the viability of cells treated with curcumin, metformin, and their combination was significantly (P < 0.05) reduced with increasing the concentration and prolonging the treatment time. Meanwhile, the combination showed a synergistic effect within 48 h. In the curcumin treated group, the expression ofBcl-2andhTERTgenes diminished. In the metformin treated group, the expression ofBaxandPUMAgenes was enhanced while the expression ofBcl-2,hTERT,mTOR, andp53genes declined. Although all treatments induced apoptosis, the combination of curcumin and metformin showed the maximum level of apoptosis, cytotoxicity, and expression ofBaxgene. The combination of curcumin and metformin showed synergistic effects within 48 h. This combination could be a potential therapeutic candidate for prostate cancer to be further investigated.
引用
收藏
页码:1026 / 1039
页数:14
相关论文
共 66 条
[41]   Metformin induces unique biological and molecular responses in triple negative breast cancer cells [J].
Liu, Bolin ;
Fan, Zeying ;
Edgerton, Susan M. ;
Deng, Xin-Sheng ;
Alimova, Irina N. ;
Lind, Stuart E. ;
Thor, Ann D. .
CELL CYCLE, 2009, 8 (13) :2031-2040
[42]   Outcomes of Localized Prostate Cancer Following Conservative Management [J].
Lu-Yao, Grace L. ;
Albertsen, Peter C. ;
Moore, Dirk F. ;
Shih, Weichung ;
Lin, Yong ;
DiPaola, Robert S. ;
Barry, Michael J. ;
Zietman, Anthony ;
O'Leary, Michael ;
Walker-Corkery, Elizabeth ;
Yao, Siu-Long .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2009, 302 (11) :1202-1209
[43]  
Matsubara H, 2012, INT J CLIN EXP PATHO, V5, P119
[44]   PUMA dissociates bax and bcl-XL to induce apoptosis in colon cancer cells [J].
Ming, Lihua ;
Wang, Peng ;
Bank, Alexander ;
Yu, Jian ;
Zhang, Lin .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (23) :16034-16042
[45]   Polymerized nano-curcumin attenuates neurological symptoms in EAE model of multiple sclerosis through down regulation of inflammatory and oxidative processes and enhancing neuroprotection and myelin repair [J].
Mohajeri, Maryam ;
Sadeghizadeh, Majid ;
Najafi, Farhood ;
Javan, Mohammad .
NEUROPHARMACOLOGY, 2015, 99 :156-167
[46]   Combination therapy in combating cancer [J].
Mokhtari, Reza Bayat ;
Homayouni, Tina S. ;
Baluch, Narges ;
Morgatskaya, Evgeniya ;
Kumar, Sushil ;
Das, Bikul ;
Yeger, Herman .
ONCOTARGET, 2017, 8 (23) :38022-38043
[47]   Recommendations for the treatment of prostate cancer in the elderly man: A study by the oncology committee of the French association of urology [J].
Mongiat-Artus, P. ;
Peyromaure, M. ;
Richaud, P. ;
Droz, J. -P. ;
Rainfray, M. ;
Jeandel, C. ;
Rebillard, X. ;
Moreau, J. -L. ;
Davin, J. -L. ;
Salomon, L. ;
Soulie, M. .
PROGRES EN UROLOGIE, 2009, 19 (11) :810-817
[48]   Induction of G1-phase cell cycle arrest and apoptosis pathway in MDA-MB-231 human breast cancer cells by sulfated polysaccharide extracted from Laurencia papillosa [J].
Murad, Hossam ;
Hawat, Mohammad ;
Ekhtiar, Adnan ;
AlJapawe, Abdulmunim ;
Abbas, Assef ;
Darwish, Hussein ;
Sbenati, Oula ;
Ghannam, Ahmed .
CANCER CELL INTERNATIONAL, 2016, 16
[49]   Drug repurposing in oncology: Compounds, pathways, phenotypes and computational approaches for colorectal cancer [J].
Nowak-Sliwinska, Patrycja ;
Scapozza, Leonardo ;
Ruiz i Altaba, Ariel .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2019, 1871 (02) :434-454
[50]   Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy [J].
Palmer, Adam C. ;
Sorger, Peter K. .
CELL, 2017, 171 (07) :1678-+