Abstract
Recent studies found that short-chain fatty acids (SCFAs), which are produced through bacterial fermentation in the gastrointestinal tract, have oncoprotective effects against cervical cancer. The most common SCFAs that are well known include acetic acid, butyric acid, and propionic acid, among which propionic acid (PA) has been reported to induce apoptosis in HeLa cells. However, the mechanism in which SCFAs suppress HeLa cell viability remain poorly understood. Our study aims to provide a more detailed look into the mechanism of PA in HeLa cells. Flow cytometry analysis revealed that PA induces reactive oxygen species (ROS), leading to the dysfunction of the mitochondrial membrane. Moreover, PA inhibits NF-κB and AKT/mTOR signaling pathways and induces LC3B protein levels, resulting in autophagy. PA also increased the sub-G1 cell population that is characteristic of cell death. Therefore, the results of this study propose that PA inhibits HeLa cell viability through a mechanism mediated by the induction of autophagy. The study also suggests a new approach for cervical cancer therapeutics.
Highlights
Among the various types of cancers known to mankind, cervical cancer is the third most common form of cancer found in cancer patients and the fourth leading cause of death among women worldwide [1,2]
To investigate the viability of propionic acid (PA) to regulate the growth of cervical cancer cell lines and the normal cell line BEAS-2B, these cells were treated with PA at concentrations ranging from 0 mM to 50 mM in 96-well plates for 48 h
HeLa cells were treated with 10 mM and 20 mM PA, which gradually changed the morphology of the cell in a concentration-dependent manner (Figure 1C)
Summary
Among the various types of cancers known to mankind, cervical cancer is the third most common form of cancer found in cancer patients and the fourth leading cause of death among women worldwide [1,2]. Significant evidence has been reported regarding how probiotic bacteria and commensal bacterial flora that form colonies in the body influence human health or pathological conditions such as cancer [8]. Especially probiotic bacteria, have been reported as central pieces in the promotion of anticancer effects and immunomodulation [9,10]. Probiotic bacteria, such as Bifidobacterium or Lactobacillus, commonly exist in human breast milk or fermented milk and have been reported to be linked to numerous health benefits [11,12]. Recent reports have described the significant roles of abnormal vaginal microbiota in cervical cancer development [14,15]. Multiple reports have proposed several mechanisms regarding the anticancer activities of LAB, including the production of anticancer metabolites (such as lactic acid and short-chain fatty acids) as well as the inhibition of cancer cells [18]
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