Abstract
Multidrug resistance (MDR) has posed a significant threat to cancer treatment and has led to the emergence of a new therapeutic regime of photodynamic therapy (PDT) to curb the menace. The PDT modality employs a photosensitiser (PS), excited at a specific wavelength of light to kill cancer cells. In the present study, we used a zinc phthalocyanine tetrasulfonic acid PS to mediate the photodynamic killing of MCF-7 cells overexpressed with P-glycoprotein (P-gp) and investigate the response to cell death induction. After photodynamic treatment, MCF-7 cells undergo cell death, and indicators like Annexin V/PI staining, DNA fragmentation, and measurement of apoptotic protein expression were investigated. Results showed increased externalisation of phosphatidylserine protein, measured as a percentage in flow cytometry indicative of apoptotic induction. This expression was significant (p < 0.006) for the untreated control cells, and there was no detection of DNA fragments after a laser fluence of 20 J/cm2. In addition, a statistically significant difference (p < 0.05) was seen in caspase 8 activity and Bax protein expression. These findings were indicative of apoptotic induction and thus seem to represent the extrinsic apoptotic pathway. This study shows the role of PDT in the treatment of a resistant phenotype breast cancer.
Highlights
Breast cancer continues to impact women and is the leading cause of global cancer incidence, with 2.3 million new cases annually [1]
We demonstrated the effect of zinc phthalocyanine tetrasulfonic acid (ZnPcS4)-mediated Photodynamic therapy (PDT) on apoptotic induction of MCF-7 cells with increased P-glycoprotein expression
The findings of the present study revealed that PDT on MCF-7/DOX cells with increased p-gp phenotype triggered the expression of caspase 8, Bax, and p53 proteins in the process of cell death
Summary
Breast cancer continues to impact women and is the leading cause of global cancer incidence, with 2.3 million new cases annually [1]. Cell death occurs through a regulated process called apoptosis, to maintain normal tissue homeostasis. When this process is evaded, cancer ensues and increases its virulence [5]. Photodynamic therapy (PDT) combines the interaction of a photosensitizer (PS) and light of appropriate wavelengths to generate a highly reactive oxygen-related species that destroys tumour cells [7,8]. This emerging procedure has the advantage of preferential destruction of tumour cells; its suggestion is a remedial therapy procedure for multidrug-resistant tumours [9,10]. PDT is a complex biochemical and photobiological reaction network, and it is essential to emphasise its usefulness in the mediation of resistant cancer death
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