Autophagy in Cervical Cancer: An Emerging Therapeutic Target

Abstract

Cervical cancer is a leading cause of morbidity and mortality in women worldwide. Although the human papillomavirus (HPV) is considered the major causative agent of cervical cancer, yet the viral infection alone is not sufficient for cancer progression. The etiopathogenesis of cervical cancer is indeed complex; a precise understanding of the complex cellular/molecular mechanisms underlying the initiation, progression and/ or prevention of the uterine cervix is therefore essential. Autophagy is emerging as an important biological mechanism in targeting human cancers, including cervical cancer. Furthermore, autophagy, a process of cytoplasm and cellular organelle degradation in lysosomes, has been implicated in homeostasis. Autophagic flux may vary depending on the cell/tissue type, thereby altering cell fate under stress conditions leading to cell survival and/or cell death. Autophagy may in turn govern tumor metastasis and subsequent carcinogenesis. Inflammation is a known hallmark of cancer. Vascular insufficiency in tumors, including cervical tissue, leads to depletion of glucose and/or oxygen perturbing the osmotic mileu causing extracellular acidosis in the tumor microenvironment that may eventually result in autophagy. Thus, targeted manipulation of complex autophagic signaling may prove to be an innovative strategy in identification of clinically relevant biomarkers in cervical cancer in the near future.

Autophagy Inhibition Promotes Gambogic Acid-induced Suppression of Growth and Apoptosis in Glioblastoma Cells

“…The induction of these two different types of autophagy may depend on different stimuli and cell types. Although the exact mechanisms of the two autophagy are not clear, it seems that the suppression of cytoprotective autophagy and the enhancement of cytotoxic autophagy might augment cytotoxic effects of anticancer drugs (Kanzawa et al, 2004;Takeuchi et al, 2005;Shingu et al, 2009;Pandey and Chandravati, 2012). In this study, we found that GA induced an apparent autophagy in GBM cells, and inhibition of autophagy could lead to enhancement of GA-mediated cytotoxicity through increasing apoptosis.…”

Sulfasalazine Induces Autophagic Cell Death in Oral Cancer Cells via Akt and ERK Pathways

“…As a result, apoptosis-related molecules have been currently a major target of cancer therapies. However, autophagy induced by various chemotherapeutic agents can augment the anti-cancer potential of drugs (Pandey and Chandravati, 2012). The mode of autophagic action in cancer cells can be classified as follows.…”

“…Although autophagy has been considered to be a cellular protective mechanism against cytotoxic agents (Eisenberg-Lerner and Kimchi, 2009), controversies regarding the roles of autophagy have recently emerged. Some researchers have suggested that the initiation of autophagy in response to chemotherapeutic agents functions as a cell death mechanism (Pandey and Chandravati, 2012). Moreover, crosstalk between autophagy and apoptosis can be complex and has seemingly contradictory roles that depend on the target cancer cell line or drug.…”

Steroidal Saponins from Paris polyphylla Induce Apoptotic Cell Death and Autophagy in A549 Human Lung Cancer Cells

“…Microtubule-associated protein light chain 3 (LC3) protein is localized in autophagosomes and autolysosomes, the amount of LC3 II cleaved product is correlated with the extent of autophagosome formation, providing the marker for the detection of autophagic activity (Kabeya et al, 2000;Pandey and Chandravati, 2012). Class III PI3K is the homologue of Beclin 1, in this regulatory frame, Beclin 1 undertakes a central role because of its necessary function in the formation of autophagic vacuoles, and results in the occurrence of autophagy (Chen and Klionsky, 2011).…”