Evaluation of Anti Cancer Effects of D PP -4 Inhibitors in Colon Cancer- An Invitro Study

Amritha, C A; Punnagai, K.; Chellathai, Darling

doi:10.7860/jcdr/2015/16015.6979

Cited by 31 publications

(32 citation statements)

References 14 publications

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“…Dipeptidyl peptidase (DPP)-4, a membrane glycoprotein, has been shown to affect multiple biological processes, such as cell differentiation, adhesion, immunomodulation, and apoptosis (7). Accumulating evidence indicates that DPP-4 plays an important role in cancer progression (8)(9)(10). A recent study confirmed that a DPP-4 inhibitor does not increase tumor incidence but may promote the metastasis of multiple cancer cell lines (11).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Dipeptidyl Peptidase-4 Accelerates Epithelial–Mesenchymal Transition and Breast Cancer Metastasis via the CXCL12/CXCR4/mTOR Axis

et al. 2019

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Dipeptidyl peptidase (DPP)-4 is a multifunctional glycoprotein involved in various biological and pathologic processes. DPP-4 has been widely recognized as a therapeutic target for type 2 diabetes mellitus but is also implicated in the development of human malignancies. Here, we show that inhibition of DPP-4 accelerates breast cancer metastasis via induction of CXCL12/CXCR4, which activates mTOR to promote epithelial-mesenchymal transition (EMT). In cultured cells, DPP-4 knockdown induced EMT and cell migration. Treatment with the DPP-4 inhibitor KR62436 (KR) promoted primary tumor growth and lung metastasis in a 4T1 tumor allograft mouse model; DPP-4 knockdown in 4T1 cells displayed similar phenotypes in vivo and in vitro. KR treatment enhanced the levels of CXCL12/CXCR4 and phosphorylated mTOR, which were associated with the induction of EMT in metastatic cancer cells. KR-induced EMT in cancer cells was inhibited by treatment with the CXCR4 inhibitor AMD3100 or the mTOR inhibitor rapamycin, and AMD3100 suppressed KR-induced metastasis in vivo. Our findings suggest that DPP-4 plays a significant role in cancer biology and that inhibition of DPP-4 promotes cancer metastasis via induction of the CXCL12/CXCR4/mTOR/EMT axis.Significance: These findings reveal that inhibition of DPP-4 increases the metastatic potential of breast cancer. This is especially important given the potential use of DPP-4 inhibition as a therapeutic strategy for type 2 diabetes.

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Section: Introductionmentioning

confidence: 99%

Inhibition of Dipeptidyl Peptidase-4 Accelerates Epithelial–Mesenchymal Transition and Breast Cancer Metastasis via the CXCL12/CXCR4/mTOR Axis

et al. 2019

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“…We found only one clinical study conducted in 2018 on the risk of colon carcinogenesis; the study reported that there was no improvement in the risk of developing colon carcinogenesis by DPP-4 inhibitors [77,78]. In in-vitro studies conducted between 2000 and 2019, there were three reports that confirmed the tumor suppressing by DPP-4 inhibitors [79][80][81], on the contrary, one study reported that the tumor suppressing effect could not be confirmed.…”

Section: Dpp-4 Inhibitorsmentioning

confidence: 85%

Diabetes Mellitus and Colon Carcinogenesis: Expectation for Inhibition of Colon Carcinogenesis by Oral Hypoglycemic Drugs

Kato

Shirakami

Shimizu

2019

Gastrointestinal Disorders

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The global deaths due to colorectal cancer and diabetes mellitus have increased by 57% and 90%, respectively. The relationship between various cancers and diabetes mellitus has been shown in multiple epidemiological studies. Hence, better management of diabetes mellitus is expected to reduce the risk of various cancers. This review focuses on colorectal cancer and aims to summarize recent findings on the antitumor effects of various oral hypoglycemic drugs on colorectal cancer and their estimated mechanisms. Of the seven classes of oral hypoglycemic agents, only metformin was found to have suppressive effects on colorectal cancer in both clinical and basic research. Clinical and basic researches on suppressing effects of glinides, dipeptidyl peptidase-4 inhibitors, thiazolidinedione, α-glucosidase inhibitors, and sodium glucose cotransporter-2 inhibitors against colon carcinogenesis have been insufficient and have not arrived at any conclusion. Therefore, further research regarding these agents is warranted. In addition, the suppressive effects of these agents in healthy subjects without diabetes should also be investigated.

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Section: Discussionmentioning

confidence: 99%

“…Few in vitro and in vivo studies have evaluated the effects of DPP4is on colorectal cancer, and the association between DPP4is use and colorectal cancer remains unclear [32][33][34]. Amritha et al [32] reported that sitagliptin exerted more potent inhibitory effects on HT-29 colon cancer cell growth than vildagliptin. However, Wang et al [33] found that saxagliptin and sitagliptin could increase cell migration and invasion in SW480 and HCT116 colon cancer cell lines through the activation of nuclear factor E2related factor 2.…”

Section: Discussionmentioning

confidence: 99%

Association between DPP-4 inhibitors and events of colorectal and liver cancers in patients with diabetes receiving second-line agents: a nested case-control study

Chou¹,

Juan²,

Chen³

et al. 2020

Preprint

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Background and aim: Several studies showed plasma dipeptidyl peptidase-4 (DPP4) levels were significantly lower in patients with colorectal and liver cancers, and animal studies also showed DPP4 inhibitors (DPP4is) have procarcinogenic effects in colorectal cancer. The aims of this study were to investigate the association between cumulative defined daily dose (cDDD) of DPP4is exposure and risks of liver and colorectal cancers in patients with type 2 diabetes mellitus. Methods In this nested case-control study, we identified 268,520 patients with diabetes receiving DPP4is as second-line agents between March 1, 2009, and December 31, 2013, from Taiwan’s National Health Insurance Research Database, Taiwan Cancer Registry, and National Death Registry of Taiwan. Of these, 948 and 990 patients newly were diagnosed with liver and colorectal cancer, respectively. The amount of DPP4is were divided into three groups (low, medium, and high) based on the interquartile range of the cDDD of the DPP4is. Results: The data showed that the low cDDD of DPP-4is was associated with a reducing risk of colorectal cancer [adjusted odds ratio (OR), 0.49; 95% CI, 0.32–0.75; P = 0.001]. However, the high cDDD of DPP-4is was associated with an increasing risk of colorectal cancer (adjusted OR, 1.86; 95% CI, 1.32–2.61; P < 0.001). No association between DPP4is use and liver cancer risk was observed. Conclusions The novel finding of this nested case study revealed a J-shaped association between the cDDD of DPP-4is and colorectal cancer risk, but not liver cancer risk. A large-based longitudinal investigation is necessary to determine whether long-term DPP4is exposure increase colorectal cancer risk.

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Evaluation of Anti Cancer Effects of D PP -4 Inhibitors in Colon Cancer- An Invitro Study

Cited by 31 publications

References 14 publications

Inhibition of Dipeptidyl Peptidase-4 Accelerates Epithelial–Mesenchymal Transition and Breast Cancer Metastasis via the CXCL12/CXCR4/mTOR Axis

Inhibition of Dipeptidyl Peptidase-4 Accelerates Epithelial–Mesenchymal Transition and Breast Cancer Metastasis via the CXCL12/CXCR4/mTOR Axis

Diabetes Mellitus and Colon Carcinogenesis: Expectation for Inhibition of Colon Carcinogenesis by Oral Hypoglycemic Drugs

Association between DPP-4 inhibitors and events of colorectal and liver cancers in patients with diabetes receiving second-line agents: a nested case-control study

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