» Articles » PMID: 18226269

Curcumin Sensitizes TRAIL-resistant Xenografts: Molecular Mechanisms of Apoptosis, Metastasis and Angiogenesis

Overview
Journal Mol Cancer
Publisher Biomed Central
Date 2008 Jan 30
PMID 18226269
Citations 55
Authors
Affiliations
Soon will be listed here.
Abstract

Background: We have recently shown that curcumin (a diferuloylmethane, the yellow pigment in turmeric) enhances apoptosis-inducing potential of TRAIL in prostate cancer PC-3 cells, and sensitizes TRAIL-resistant LNCaP cells in vitro through multiple mechanisms. The objectives of this study were to investigate the molecular mechanisms by which curcumin sensitized TRAIL-resistant LNCaP xenografts in vivo.

Methods: Prostate cancer TRAIL-resistant LNCaP cells were implanted in Balb c nude mice to examine the effects of curcumin and/or TRAIL on tumor growth and genes related to apoptosis, metastasis and angiogenesis.

Results: Curcumin inhibited growth of LNCaP xenografts in nude mice by inducing apoptosis (TUNEL staining) and inhibiting proliferation (PCNA and Ki67 staining), and sensitized these tumors to undergo apoptosis by TRAIL. In xenogrfated tumors, curcumin upregulated the expression of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax, Bak, p21/WAF1, and p27/KIP1, and inhibited the activation of NFkappaB and its gene products such as cyclin D1, VEGF, uPA, MMP-2, MMP-9, Bcl-2 and Bcl-XL. The regulation of death receptors and members of Bcl-2 family, and inactivation of NFkappaB may sensitize TRAIL-resistant LNCaP xenografts. Curcumin also inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells in mice.

Conclusion: The ability of curcumin to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that curcumin alone or in combination with TRAIL can be used for prostate cancer prevention and/or therapy.

Citing Articles

Prostate cancer microenvironment: multidimensional regulation of immune cells, vascular system, stromal cells, and microbiota.

Chen L, Xu Y, Wang Y, Ren Y, Dong X, Wu P Mol Cancer. 2024; 23(1):229.

PMID: 39395984 PMC: 11470719. DOI: 10.1186/s12943-024-02137-1.


Inflammation in Prostate Cancer: Exploring the Promising Role of Phenolic Compounds as an Innovative Therapeutic Approach.

Fernandes R, Costa C, Fernandes R, Barros A Biomedicines. 2023; 11(12).

PMID: 38137361 PMC: 10740737. DOI: 10.3390/biomedicines11123140.


Effects of curcumin and ursolic acid in prostate cancer: A systematic review.

Besasie B, Saha A, DiGiovanni J, Liss M Urologia. 2023; 91(1):90-106.

PMID: 37776274 PMC: 10976464. DOI: 10.1177/03915603231202304.


Curcuminoids as Anticancer Drugs: Pleiotropic Effects, Potential for Metabolic Reprogramming and Prospects for the Future.

Pouliquen D, Gall Troselj K, Anto R Pharmaceutics. 2023; 15(6).

PMID: 37376060 PMC: 10303184. DOI: 10.3390/pharmaceutics15061612.


The Involvement of Natural Polyphenols in Molecular Mechanisms Inducing Apoptosis in Tumor Cells: A Promising Adjuvant in Cancer Therapy.

Chimento A, De Luca A, DAmico M, De Amicis F, Pezzi V Int J Mol Sci. 2023; 24(2).

PMID: 36675194 PMC: 9863215. DOI: 10.3390/ijms24021680.


References
1.
Srivastava R, Chen Q, Siddiqui I, Sarva K, Shankar S . Linkage of curcumin-induced cell cycle arrest and apoptosis by cyclin-dependent kinase inhibitor p21(/WAF1/CIP1). Cell Cycle. 2007; 6(23):2953-61. DOI: 10.4161/cc.6.23.4951. View

2.
Shankar S, Singh T, Chen X, Thakkar H, Firnin J, Srivastava R . The sequential treatment with ionizing radiation followed by TRAIL/Apo-2L reduces tumor growth and induces apoptosis of breast tumor xenografts in nude mice. Int J Oncol. 2004; 24(5):1133-40. View

3.
Shankar S, Srivastava R . Enhancement of therapeutic potential of TRAIL by cancer chemotherapy and irradiation: mechanisms and clinical implications. Drug Resist Updat. 2004; 7(2):139-56. DOI: 10.1016/j.drup.2004.03.002. View

4.
Liu X, Yue P, Khuri F, Sun S . p53 upregulates death receptor 4 expression through an intronic p53 binding site. Cancer Res. 2004; 64(15):5078-83. DOI: 10.1158/0008-5472.CAN-04-1195. View

5.
Ghosh S, May M, Kopp E . NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol. 1998; 16:225-60. DOI: 10.1146/annurev.immunol.16.1.225. View