Probiotics and Antimicrobial Proteins

Probiotics: A New Approach for the Prevention and Treatment of Cervical Cancer

Cervical cancer is closely linked to high-risk human papillomavirus (HR-HPV) infections which could crosstalk with the diversity of microorganisms within the cervicovaginal microbiota (CVM). Conventional treatments can disrupt the host microbial communities, which in turn affect the efficacy and side effects of these interventions, potentially jeopardizing the lives and health of patients. Therefore, there is a need to develop new approaches for the prevention and treatment of cervical cancer, and probiotics have shown significant potential as effective agents against cervical cancer. Studies have demonstrated that probiotics induce anticancer action by inducing apoptosis in tumor cells, inhibiting metastasis, reducing inflammation, enhancing immune functions, and modifying the effect of chemo/radiation therapy. Recent reports showed that probiotics had the ability to restore the CVM, clear HPV infections in cervical epithelial cells, and modulate immune responses. Despite these promising findings, the efficacy and safety of probiotic formulations require further validation through comprehensive research. This review focused on elucidating the mechanism behind the anticancer action and the importance of addressing the challenges associated with the clinical application of probiotics to realize their full potential as a novel and complementary approach in the prevention and treatment of cervical cancer.

It Is All about Probiotics to Control Cervical Cancer

Cervical cancer (CC) is the fourth most common malignancy in female patients. "Human papillomavirus" (HPV) contamination is a leading cause of all forms of cervical cancer, accounting for an expected 570,000 reported incidents in 2018. Two HPV strains (16 and 18) are responsible for 70% of CC and pre-cancerous cervical abnormalities. CC is one of the foremost reasons for the malignancy death rate in India among women ranging from 30 to 69 years of age in India, responsible for 17% of all cancer deaths. Currently approved cervical cancer treatments are associated with adverse reactions that might harm the lives of women affected by this disease. Consequently, probiotics can play a vital role in the treatment of CC. It is reflected from various studies regarding the role of probiotics in the diagnosis, prevention or treatment of cancer. In this review article, we have discussed the rationale of probiotics for treatment of CC, the role of probiotics as effective adjuvants in anti-cancer therapy and the combined effect of the anti-cancer drug along with probiotics to minimize the side effects due to chemotherapy.

Lacticaseibacillus casei LH23 Suppressed HPV Gene Expression and Inhibited Cervical Cancer Cells

Microbiota of lower female reproductive tract is special in its microorganism composition with Lactobacillus as the predominant bacteria. A few of Lactobacillus species have been identified to benefit the inhibition of inflammatory and malignant diseases. Lacticaseibacillus casei LH23 is a strain isolated from traditional fermented food and had been demonstrate to ameliorate DSS-induced colitis in mice. In the present study, effects of Lacticaseibacillus casei LH23 on cervical cancer cells were investigated. Supernatants of lysates and heat-inactivated Lacticaseibacillus casei LH23 were found to inhibit the expression of human papillomavirus genes E6/E7 which is the main causative factor of cervical cancer. With MTT, EdU staining, and TUNEL staining assays, Lacticaseibacillus casei LH23 was shown to suppress the proliferation and induced the apoptosis of cervical cancer cells. Additionally, with wound-healing and Western-blot assays, Lacticaseibacillus casei LH23 was shown to slowdown the migration of cervical cancer cells and altered the expression of metastasis-related genes. These results demonstrated the anti-cervical cancer potential of Lacticaseibacillus casei LH23.

Mycosubtilin Induces G1 Phase Block and Autophagy in Cervical Cancer HeLa Cells

Cyclic lipopeptides secreted by the probiotic bacterium Bacillus subtilis have attracted much attention due to their antitumor activities and low toxicity. However, the role of Mycosubtilin (Myco) in the prevention and treatment of cervical cancer remains unclear. In the present study, we conducted a systematic evaluation of Myco's anti-cervical cancer effects to identify its molecular mechanism of action using proteomics technology. The results reveal that Myco inhibited the growth of HeLa and SiHa cervical cancer cell lines in a dose-dependent (3-15 µg/mL) and time-dependent (12-48 h) manner and significantly reduced colony formation and migration in HeLa cells, highlighting its potential to suppress tumor spread. Moreover, autophagosome and autolysosome numbers were significantly increased after Myco treatment, and the expression of autophagy-related proteins was significantly modulated, suggesting that autophagy plays a role in its anti-cancer mechanism. Myco treatment also induced G1 phase cell cycle arrest in HeLa cells, as confirmed by proteomics analysis. Myco was shown to induce cell cycle arrest in HeLa cells by regulating the P53 pathway and autophagy-dependent cell death via the PI3K/AKT/mTOR signaling pathway, demonstrating its multidimensional effect on cervical cancer cell growths. Myco treatment significantly inhibited tumor growth in vivo in a nude mouse cervical cancer xenograft model, providing direct evidence of its potential as a therapeutic candidate for cervical cancer. Given its unique anti-cancer mechanism and significant therapeutic efficacy, Myco should be considered a promising therapeutic agent for cervical cancer.