Involvement and targeted intervention of benzo(a)pyrene-regulated apoptosis related proteome modification and muti-drug resistance in hepatocellular carcinoma

Abstract

During the development of hepatocellular carcinoma (HCC), the mutual adaptation and interaction of HCC cells and the microenvironment play an important role. Benzo(a)pyrene (B[a]P) is a common environmental pollutant, which can induce the initiation of various malignant tumors, including HCC. However, the effects of B[a]P exposure on progression of HCC and the potential mechanisms remains largely uninvestigated. Here we found that, after the long-term exposure of HCC cells to low dose of B[a]P, it activated glucose-regulated protein 75 (GRP75), which then induced a modification of apoptosis-related proteome. Among them, we identified the X-linked inhibitor of apoptosis protein (XIAP) as a key downstream factor. XIAP further blocked the caspase cascade activation and promoted the acquisition of the anti-apoptosis abilities, ultimately leading to multi-drug resistance (MDR) in HCC. Furthermore, the abovementioned effects were markedly attenuated when we inhibited GRP75 by using 3,4-dihydroxycinnamic acid (caffeic acid, CaA). Collectively, our present study revealed the effects of B[a]P exposure on the progression of HCC, and identified GRP75 was a meaningful factor involved in.

Caffeic acid, a dietary polyphenol pre-sensitizes PDAC to chemotherapeutic drug

“…S2. These results are in correspondence to recent studies which have reported that CFA at concentrations of 20µM shows inhibitory effects on hepatocellular carcinoma [44].…”

Effective therapy of advanced breast cancer through synergistic anticancer by paclitaxel and P-glycoprotein inhibitor

“…XIAP is an apoptotic protein that plays an important role in MDR by blocking the activation of the caspase cascade and promoting anti-apoptotic abilities [ 47 ]. Western blotting showed an obvious specific band in the Taxol® treated group, owing to chemotherapeutic stimulation ( Fig.…”

Mitophagy and clear cell renal cell carcinoma: insights from single-cell and spatial transcriptomics analysis

“…In ccRCC, abnormalities in mitophagy may be caused by various factors, including changes in the intracellular and extracellular environment, genetic mutations, and dysregulation of regulatory pathways ( 17 ). These abnormalities not only affect the survival and proliferation of tumor cells but may also impact tumor development, invasion, and drug resistance ( 18 ).…”