Cytotoxic Effects of Combinative ZnPcS4 Photosensitizer Photodynamic Therapy (PDT) and Cannabidiol (CBD) on a Cervical Cancer Cell Line

Abstract

The most prevalent type of gynecological malignancy globally is cervical cancer (CC). Complicated by tumor resistance and metastasis, it remains the leading cause of cancer deaths in women in South Africa. Early CC is managed by hysterectomy, chemotherapy, radiation, and more recently, immunotherapy. Although these treatments provide clinical benefits, many patients experience adverse effects and secondary CC spread. To minimize this, novel and innovative treatment methods need to be investigated. Photodynamic therapy (PDT) is an advantageous treatment modality that is non-invasive, with limited side effects. The Cannabis sativa L. plant isolate, cannabidiol (CBD), has anti-cancer effects, which inhibit tumor growth and spread. This study investigated the cytotoxic combinative effect of PDT and CBD on CC HeLa cells. The effects were assessed by exposing in vitro HeLa CC-cultured cells to varying doses of ZnPcS4 photosensitizer (PS) PDT and CBD, with a fluency of 10 J/cm2 and 673 nm irradiation. HeLa CC cells, which received the predetermined lowest dose concentrations (ICD50) of 0.125 µM ZnPcS4 PS plus 0.5 µM CBD to yield 50% cytotoxicity post-laser irradiation, reported highly significant and advantageous forms of cell death. Flow cytometry cell death pathway quantitative analysis showed that only 13% of HeLa cells were found to be viable, 7% were in early apoptosis and 64% were in late favorable forms of apoptotic cell death, with a minor 16% of necrosis post-PDT. Findings suggest that this combined treatment approach can possibly induce primary cellular destruction, as well as limit CC metastatic spread, and so warrants further investigation.

Cannabidiol Combination Enhances Photodynamic Therapy Effects on MCF-7 Breast Cancer Cells

“…Many studies have shown that cannabinoids can influence the rate of cell proliferation, migration, angiogenesis, and apoptosis, especially in breast, prostate, and glioma cell lines [45][46][47]. Studies have also revealed that the combination of CBD with PDT enhances the treatment efficacies in various cancers, such as metastatic melanoma [48], cervical cancer [49,50], colorectal cancer [51], etc. Similarly to these reports, this study showed the enhanced therapeutic potential of CBD and PDT in breast cancer cells by upregulating the activity of apoptotic proteins.…”

Nano‐phototherapy: Favorable prospects for cancer treatment

“…Red light activation of the PS results in the production of singlet oxygen ( 1 O 2 ) and harmful ROS. This cytotoxic species production causes oxidative stress, which may lead to apoptosis (Razlog et al, 2023). Although, it has been established that PDT is a tumor‐specific therapeutic criteria, its uses are severely hampered by the hypoxic tumor microenvironment (TME) (Hu et al, 2018).…”