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Combined use of arginase and dichloroacetate exhibits anti-proliferative effects in triple negative breast cancer cells
Angela Verma1; Yau-Min Lam2; Yun-Chung Leung2; Xiaohui Hu1; Xin Chen1; Edwin Cheung1; Kin Yip Tam1
2019-03
Source PublicationJOURNAL OF PHARMACY AND PHARMACOLOGY
ISSN0022-3573
Volume71Issue:3Pages:306-315
Abstract

Objectives

Drug combination in cancer therapy aims to achieve synergistic therapeutic effect, reduced drug dosage, reduced drug toxicity and minimizes or delays the induction of drug resistance. In the present study, we investigated the anticancer effects of the combination of two metabolic modulators, dichloroacetate (DCA) and bacillus caldovelox arginase (BCA) (or pegyated human arginase (HA)).

Methods

The combination treatments were evaluated in MCF‐7 and MDA‐MB 231 cells as well as in MDA‐MB 231 breast cancer xenograft model.

Key findings

Dichloroacetate and BCA combination exhibited anti‐proliferative effects on MCF‐7 cells, which were found to be synergistic. Analysis of the gene expression upon drug treatments revealed that the synergistic anti‐proliferative effect on MCF‐7 cells was possibly in part due to the activation of the p53 pathway. A similar synergistic anti‐proliferative effect was observed in the combined use of DCA and HA on MCF‐7 and MDA‐MB231 cells, which was due to induction of cell cycle arrest at G2/M phase. Moreover, the combination enhanced anti‐tumour activity in a MDA‐MB 231 xenograft mouse model.

Conclusions

Our results suggested that dichloroacetate and arginase combination exhibited enhanced anti‐cancer effects in preclinical breast cancer models which may offer an additional treatment option for breast cancer.

KeywordBacillus Caldovelox Arginase Breast Cancer Dichloroacetate Drug Combination Pegyated Human Arginase
DOI10.1111/jphp.13033
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000457750000002
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Document TypeJournal article
CollectionFaculty of Health Sciences
Institute of Chinese Medical Sciences
Affiliation1.Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau
2.Department of Applied Biology and Chemical Technology, LoKa Chung Centre for Natural Anti-Cancer Drug Development, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China
First Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Angela Verma,Yau-Min Lam,Yun-Chung Leung,et al. Combined use of arginase and dichloroacetate exhibits anti-proliferative effects in triple negative breast cancer cells[J]. JOURNAL OF PHARMACY AND PHARMACOLOGY,2019,71(3):306-315.
APA Angela Verma.,Yau-Min Lam.,Yun-Chung Leung.,Xiaohui Hu.,Xin Chen.,...&Kin Yip Tam.(2019).Combined use of arginase and dichloroacetate exhibits anti-proliferative effects in triple negative breast cancer cells.JOURNAL OF PHARMACY AND PHARMACOLOGY,71(3),306-315.
MLA Angela Verma,et al."Combined use of arginase and dichloroacetate exhibits anti-proliferative effects in triple negative breast cancer cells".JOURNAL OF PHARMACY AND PHARMACOLOGY 71.3(2019):306-315.
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