4.7 Article

The Anticancer Effects of Garlic Extracts on Bladder Cancer Compared to Cisplatin: A Common Mechanism of Action via Centromere Protein M

Journal

AMERICAN JOURNAL OF CHINESE MEDICINE
Volume 46, Issue 3, Pages 689-705

Publisher

WORLD SCIENTIFIC PUBL CO PTE LTD
DOI: 10.1142/S0192415X18500362

Keywords

Garlic; Urinary Bladder Neoplasms; Microarray Analysis; Gene Regulatory Networks

Funding

  1. National Research Foundation of Korea (NRF) - Korean government (MSP) [2014R1A2A2A04007036]
  2. Functional Districts of the Science Belt support program, Ministry of Science, ICT and Future Planning [2016K000297]
  3. Chungbuk National University
  4. National Research Foundation of Korea [2014R1A2A2A04007036] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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Although garlic induces apoptosis in cancer cells, it is unclear whether the effects are similar to those of cisplatin against bladder cancer (BC). Therefore, this study investigated whether garlic extracts and cisplatin show similar activity when used to treat BC. The effect of garlic on T24 BC cell line was examined in a BALB/C-nude mouse xenograft model and compared with that of cisplatin. Tissue microarray analysis and gene network analysis were performed to identify differences in gene expression by control tumors and tumors exposed to garlic extract or cisplatin. Investigation of gene expression based on tissues from 165 BC patients and normal controls was then performed to identify common targets of garlic and cisplatin. Tumor volume and tumor weight in cisplatin (0.05 mg/kg)- and garlictreated mice were significantly smaller than those in negative control mice. However, cisplatin-treated mice also showed a significant reduction in body weight. Microarray analysis of tumor tissue identified 515 common anticancer genes in the garlic and cisplatin groups (p < 0: 01). Gene network analysis of 252 of these genes using the Cytoscape and ClueGo software packages mapped 17 genes and 9 gene ontologies to gene networks. BC (NMIBC and MIBC) patients with low expression of centromere protein M (CENPM) showed significantly better progression-free survival than those with high expression. Garlic extract shows anticancer activity in vivo similar to that of cisplatin, with no evident of side effects. Both appear to act by targeting protein-DNA complex assembly; in particular, expression of CENPM.

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