B-Cell Lymphoma 2 Mitochondria-Mediated Apoptotic Pathway in Cervical Carcinoma

Cervical carcinoma is a leading cause of female malignant-depended morbidity and mortality worldwide. Although modern gynecological screening, including Papanicolaou (PAP) test and human papillomavirus (HPV) DNA/m RNA tests, provides an optimal management in female health, there is an increasing need for understanding the role of specific molecular pathways implicated in the disease. Among them, apoptosis plays a crucial role in the progression of the malignancy and also in the response rates to chemo-targeted therapeutic regimens.

The purpose of the current molecular review was to explore the role of mitochondrial-based anti-apoptotic and apoptotic pathways in cervical carcinoma molecular substrate and their established and also potential chemo-targeted inhibitors.

A systematic review of the literature was carried out based on the international database PubMed including 50 significant papers in the examined scientific field. The following keywords were used: apoptosis, mitochondria, cervical, carcinoma, B-cell lymphoma.

B-cell lymphoma (BCL) proteins' expression in cervical carcinoma demonstrates differences among the corresponding patients. Especially, overactivation of BCL-2 seems to lead in an aggressive cervical carcinoma phenotype (advanced stage, poor prognosis) due to its strong anti-apoptotic action.

Mitochondria play a crucial role in the apoptotic phenomenon regarding cervical carcinoma. BCL-2 overexpression induces the resistant to normal apoptotic signalling pathway leading to an immortalization-like status of the malignant cells. This event is crucial for the survival and response rates in the patients with BCL-2 abnormal activity. Furthermore, it seems that high risk HPV types activate BCL-2 by the increased oncogenic influence of E6/E7 viral genes. For these reasons, a broad spectrum of anti-BCL-2 inhibitors is under experimental, basic research and clinical evaluation regarding cervical carcinoma patients.