C118P exerted potent anti-tumor effects against melanoma with induction of G2/M arrest via inhibiting the expression of BUB1B

Zhou, Meng; Wang, Cheng; Yuan, Shengtao; Li, Hongyang

doi:10.1016/j.jdermsci.2022.11.003

Cited by 1 publication

(1 citation statement)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, other targets of C118P are not excluded. C118P showed antitumour effects against melanoma via BUB1B or against HCC via tumour vasculature [36,37]. In addition, our other studies have shown that C118P inhibited breast cancer metastasis through ASCT2.…”

Section: Discussionmentioning

confidence: 80%

A Novel ASCT2 Inhibitor, C118P, Blocks Glutamine Transport and Exhibits Antitumour Efficacy in Breast Cancer

Lyu,

Liu,

Wang

et al. 2023

Cancers

View full text Add to dashboard Cite

Background: The microtubule protein inhibitor C118P shows excellent anti-breast cancer effects. However, the potential targets and mechanisms of C118P in breast cancer remain unknown. Methods: Real-time cellular analysis (RTCA) was used to detect cell viability. Apoptosis and the cell cycle were detected by flow cytometry. Computer docking simulations, surface plasmon resonance (SPR) technology, and microscale thermophoresis (MST) were conducted to study the interaction between C118P and alanine-serine-cysteine transporter 2 (ASCT2). Seahorse XF technology was used to measure the basal oxygen consumption rate (OCR). The effect of C118P in the adipose microenvironment was explored using a co-culture model of adipocytes and breast cancer cells and mouse cytokine chip. Results: C118P inhibited proliferation, potentiated apoptosis, and induced G2/M cell cycle arrest in breast cancer cells. Notably, ASCT2 was validated as a C118P target through reverse docking, SPR, and MST. C118P suppressed glutamine metabolism and mediated autophagy via ASCT2. Similar results were obtained in the adipocyte–breast cancer microenvironment. Adipose-derived interleukin-6 (IL-6) promoted the proliferation of breast cancer cells by enhancing glutamine metabolism via ASCT2. C118P inhibited the upregulation of ASCT2 by inhibiting the effect of IL-6 in co-cultures. Conclusion: C118P exerts an antitumour effect against breast cancer via the glutamine transporter ASCT2.

show abstract

Section: Discussionmentioning

confidence: 80%