Vildagliptin, a dipeptidyl peptidase-4 inhibitor, reduces betel-nut induced carcinogenesis in female mice

Nath, Moumita; Bhattacharjee, Kasturi; Choudhury, Yashmin

doi:10.1016/j.lfs.2020.118870

Cited by 6 publications

(2 citation statements)

References 68 publications

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“…In our recent review on the therapeutic potential of repurposing the incretin-based therapies in breast cancer, we explored all the plausible molecular mechanism(s) of DPP-IV inhibitors and GLP-1 agonists along with the cancerpromoting role of DPP-IV (Jaiswal et al, 2022). Recently, we also reported the anti-cancer role of AMPK activator, 5aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) via increased expression of mitochondrial biogenesis related genes PGC-1α, NRF-1, NRF-2, and TFAM (Tripathi et al, 2022) which is in line with the reports available on the AMPK activation by sitagliptin, vildagliptin and exendin-4 (Zheng et al, 2018;Nath et al, 2021;Li et al, 2021). These reports provided another clue for the therapeutic potential of sitagliptin, vildagliptin, and exendin-4 on breast cancer, possibly via the promotion of mitochondrial biosynthesis.…”

Section: Introductionsupporting

confidence: 87%

Anti-cancer effects of sitagliptin, vildagliptin, and exendin-4 on triple-negative breast cancer cells via mitochondrial modulation

Jaiswal¹,

Tripathi²,

ASSAIYA³

et al. 2022

Biocell

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Triple-negative breast cancer (TNBC) cell line MDA-MB-231 is known for Warburg metabolism and defects in mitochondria. On the other hand, dipeptidyl peptidase-IV (DPP-IV) inhibitors such as sitagliptin and vildagliptin and GLP-1 agonist exendin-4 are known to improve mitochondrial functions as well as biogenesis, but no study has evaluated the influence of these drugs on mitochondrial biogenesis on metastatic breast cancer cell line. We have recently reported anticancer effects of 5-aminoimidazole-4-carboxamide riboside on MDA-MB-231 cells via activation of AMP-dependent kinase (AMPK), which activates the downstream transcription factors PGC-1α, PGC-1β, or FOXO1 for mitochondrial biogenesis; above-mentioned incretin-based therapies are also known to activate AMPK. This study evaluated the effects of sitagliptin, vildagliptin, and exendin-4 on MDA-MB-231 cells and the underlying changes in mitochondrial biogenesis, were examined. Treatment with sitagliptin (100 µM), vildagliptin (100 µM), and exendin-4 (10 nM) for 72 h to MDA-MB-231 cells led to a decrease in viability indicated by MTT assay, cell migration by scratch, and transwell migration assays, accompanied with marginal reduction in cell numbers along with the apoptotic appearance, the rate of apoptosis, and decreased lactate content in conditioned medium. These changes in the cancer phenotype were accompanied by an increase in the mitochondrial DNA to nuclear DNA ratio, increased MitoTracker green and red staining, and increased expression of transcription factors PGC-1α, NRF-1, NRF-2, TFAM, and HO-1. Pre-treatment of cells with these incretin-based drugs followed by 48 h treatment with 1 µM doxorubicin increased doxorubicin sensitivity as observed by a decrease in viability by MTT assay. Thus, sitagliptin, vildagliptin, and exendin-4 exert their beneficial effects on TNBC cells via an increase in mitochondrial biogenesis that helps to switch Warburg metabolism into anti-Warburg effect. Therapeutic response was in the order of: sitagliptin > vildagliptin > exendin-4.

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Section: Introductionsupporting

confidence: 87%

Anti-cancer effects of sitagliptin, vildagliptin, and exendin-4 on triple-negative breast cancer cells via mitochondrial modulation

Jaiswal¹,

Tripathi²,

ASSAIYA³

et al. 2022

Biocell

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show abstract

“…CD26/DPP4 plays an important role in several types of cancer ( 27-31 ) and DPP-4 inhibitors are being evaluated as treatments for cancer. Certain studies have indicated that anagliptin may inhibit the proliferation of tumor cells ( 32 , 33 ).…”

Section: Discussionmentioning

confidence: 99%

Anagliptin promotes apoptosis in mouse colon carcinoma cells via MCT‑4/lactate‑mediated intracellular acidosis

Qin

Kou

et al. 2022

Exp Ther Med

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Investigation into the role of anti-diabetic agents in cachexia associated with metastatic cancer

Bora

Patel²

2021

Life Sciences

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Vildagliptin, a dipeptidyl peptidase-4 inhibitor, reduces betel-nut induced carcinogenesis in female mice

Cited by 6 publications

References 68 publications

Anti-cancer effects of sitagliptin, vildagliptin, and exendin-4 on triple-negative breast cancer cells via mitochondrial modulation

Anti-cancer effects of sitagliptin, vildagliptin, and exendin-4 on triple-negative breast cancer cells via mitochondrial modulation

Anagliptin promotes apoptosis in mouse colon carcinoma cells via MCT‑4/lactate‑mediated intracellular acidosis

Investigation into the role of anti-diabetic agents in cachexia associated with metastatic cancer

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