ASCORBYL PALMITATE ENHANCES ANTI-PROLIFERATIVE EFFECT OF TRASTUZUMAB IN HER2-POSITIVE BREAST CANCER CELLS.

Abstract

Background: Breast cancer (BC) accounts for about 30% of cancers in women, with a mortality rate of around 15%. HER2- positive BC, an aggressive subtype, represents 15-20% of all BC cases. High-dose vitamin C has shown antitumor effects by increasing reactive oxygen species in cancer cells without significant toxicity.

Aim: This study aimed to explore an in vitro dual treatment using ascorbyl palmitate (AP), a lipophilic vitamin C derivative, and trastuzumab, an HER2 receptor blocker.

Materials and methods: HER2-positive SK-BR-3 BC cells were treated with AP, trastuzumab, or their combination. The cell survival MTT assay, apoptosis, and cell cycle phase analysis were conducted using flow cytometry, while mRNA and protein expression were assessed using RT-qPCR and Western blot methods. Ki-67 expression was evaluated by immunofluorescence assay.

Results: AP reduced cell viability in a time- and dose-dependent manner, and its combination with trastuzumab further decreased cell viability. A cytometric analysis showed enhanced apoptosis after combination treatment. mRNA analysis revealed upregulated TP53 mRNA expression, along with upregulation of BAX, CYCS, CASP3, and CASP8 gene expression, while the BCL-2 and BCL2L1 genes were downregulated, further supporting the induction of apoptosis. The antiproliferative effectiveness of the combination therapy was demonstrated by a Western blot assay, which showed suppression of phospho-P38, ERK1/2, and PI3K protein synthesis.

Conclusion: These results underscore the potential effects of combining AP and trastuzumab in BC treatment, guiding future therapeutic strategies.