Presently, cancer is one of the leading causes of death in the world, primarily due to tumor heterogeneity associated with high-grade malignancy. Tumor heterogeneity poses a tremendous challenge, especially with the emergence of resistance not only to chemo- and radiation- therapies, but also to immunotherapy using monoclonal antibodies. The use of Salmonella, as a highly selective and penetrative antitumor agent, has shown convincing results, thus meriting further investigation. In this review, the mechanisms used by Salmonella in combating cancer are carefully explained. In essence, Salmonella overcomes the suppressive nature of the tumor microenvironment and coaxes the activation of tumor-specific immune cells to induce cell death by apoptosis and autophagy. Furthermore, Salmonella treatment suppresses tumor aggressive behavior via inhibition of angiogenesis and delay of metastatic activity. Thus, harnessing the natural potential of Salmonella in eliminating tumors will provide an avenue for the development of a promising micro-based therapeutic agent that could be further enhanced to address a wide range of tumor types.

Opinion statement: The primordial autophagy process, originally identified as a starvation response in baker’s yeast, has since been shown to have a wide spectrum of functions other than survival. In many cases, it is accepted that autophagy operates as a key tumor suppressor mechanism that protects cells from adverse environmental cues by enforcing homeostasis and maintaining the functional and structural integrity of organelles. Paradoxically, heightened states of autophagy are also seen in some cancers, leading to the prevailing view that the pro-survival aspect of autophagy might be hijacked by some tumors to promote their fitness and pathogenesis. Notably, recent studies have revealed a broad range of cell-autonomous autophagy in reshaping tumor microenvironment and maintaining lineage integrity and immune homeostasis, calling for a renewed understanding of autophagy beyond its classical roles in cell survival. Here, we evaluate the increasing body of literature that argues the “double-edged” consequences of autophagy manipulation in cancer therapy, with a particular focus on highly plastic and mutagenic melanoma. We also discuss the caveats that must be considered when evaluating whether autophagy blockade is the effector mechanism of some anti-cancer therapy particularly associated with lysosomotropic agents. If autophagy proteins are to be properly exploited as targets for anticancer drugs, their diverse and complex roles should also be considered.

Immunotherapy is becoming a popular treatment modality in combat against cancer, one of the world’s leading health problems. While tumor cells influence host immunity via expressing immune inhibitory signaling proteins, some bacteria possess immunomodulatory activities that counter the symptoms of tumors. The accumulation of Salmonella in tumor sites influences tumor protein expression, resulting in T cell infiltration. However, the molecular mechanism by which Salmonella activates T cells remains elusive. Many tumors have been reported to have high expressions of programmed death-ligand 1 (PD-L1), which is an important immune checkpoint molecule involved in tumor immune escape. In this study, Salmonella reduced the expression of PD-L1 in tumor cells. The expression levels of phospho-protein kinase B (P-AKT), phospho-mammalian targets of rapamycin (P-mTOR), and the phospho-p70 ribosomal s6 kinase (P-p70s6K) pathway were revealed to be involved in the Salmonella-mediated downregulation of PD-L1. In a tumor-T cell coculture system, Salmonella increased T cell number and reduced T cell apoptosis. Systemic administration of Salmonella reduced the expressions of PD-L-1 in tumor-bearing mice. In addition, tumor growth was significantly inhibited along with an enhanced T cell infiltration following Salmonella treatment. These findings suggest that Salmonella acts upon the immune checkpoint, primarily PD-L1, to incapacitate protumor effects and thereby inhibit tumor growth.

Heparanase cleaves the extracellular matrix by degrading heparan sulfate that ultimately leads to cell invasion and metastasis; a condition that causes high mortality among cancer patients. Many of the anticancer drugs available today are natural products of plant origin, such as hinokitiol. In the previous report, it was revealed that hinokitiol plays an essential role in anti-inflammatory and anti-oxidation processes and promote apoptosis or autophagy resulting to the inhibition of tumor growth and differentiation. Therefore, this study explored the effects of hinokitiol on the cancer-promoting pathway in mouse melanoma (B16F10) and breast (4T1) cancer cells, with emphasis on heparanase expression. We detected whether hinokitiol can elicit anti-metastatic effects on cancer cells via wound healing and Transwell assays. Besides, mice experiment was conducted to observe the impact of hinokitiol in vivo. Our results show that hinokitiol can inhibit the expression of heparanase by reducing the phosphorylation of protein kinase B (Akt) and extracellular regulated protein kinase (ERK). Furthermore, in vitro cell migration assay showed that heparanase downregulation by hinokitiol led to a decrease in metastatic activity which is consistent with the findings in the in vivo experiment.

Context: The study investigated the medicinal properties of Spathiphyllum cannifolium (Dryand. ex Sims) Schott as a possible source of antimicrobial compounds. Materials and Methods: The phytochemical constituents were screened using qualitative methods and the antibacterial and antifungal activities were determined using agar well diffusion method. Statistical Analysis: One-way analysis of variance and Fisher’s least significant difference test were used. Results: The phytochemical screening showed the presence of sterols, flavonoids, alkaloids, saponins, glycosides, and tannins in both ethanol and chloroform leaf extracts, but triterpenes were detected only in the ethanol leaf extract. The antimicrobial assay revealed that the chloroform leaf extract inhibited Candida albicans, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa, whereas the ethanol leaf extract inhibited E. coli, S. aureus, and B. subtilis only. The ethanol and chloroform leaf extracts exhibited the highest zone of inhibition against B. subtilis. The antifungal assay showed that both the leaf extracts have no bioactivity against Aspergillus niger and C. albicans. Conclusions: Results suggest that chloroform is the better solvent for the extraction of antimicrobial compounds against the test organisms used in this study. Findings of this research will add new knowledge in advancing drug discovery and development in the Philippines.

Bacteria-mediated cancer therapy (BMCT) is an emerging tool that may advance potential approaches in cancer immunotherapy, whereby tumors are eradicated by the hosts’ immune system upon recruitment and activation by bacteria such as Salmonella. This paper provides an emphasis on the immunomodulatory effects that encompasses both the innate and adaptive immune responses inherently triggered by Salmonella. Furthermore, modifications of Salmonella-based treatment in the attempt to improve tumor-specific immune responses including cytokine therapy, gene therapy, and DNA vaccine delivery are likewise discussed. The majority of the findings described herein incorporate cell-based experiments and murine model studies, and only a few accounts describe clinical trials. Salmonella-based cancer therapy is still under development; nonetheless, the pre-clinical research and early-phase clinical trials that have been completed so far have shown promising and convincing results. Certainly, the continuous development of, and innovation on, Salmonella-based therapy could pave the way for its eventual emergence as one of the mainstream therapeutic interventions addressing various types of cancer.