Tumour Growth Inhibition and Systemic Responses of ΔsopBΔsopDΔpipD Disrupted Salmonella Agona and Salmonella Typhimurium in Mice

@#Introduction: Bacteria had long been known to have tumour-targeting and tumour inhibition capabilities and have re-emerged into the limelight of cancer research as a possible alternative treatment for solid tumours. Conventional therapies for solid tumours are either by surgery, chemotherapy, radiotherapy, which are very invasive and non-specific to the tumours and results in various adverse effects on the patients. Bacterial Mediated Tumour Therapy often utilises attenuated bacteria as therapeutic agents to ensure reduced pathogenicity of the strains. However, this often results in lower invasiveness towards the tumours itself. In this study, we studied the tumour inhibition capabilities of Salmonella Pathogenicity Island (SPI) attenuated Salmonella Typhimurium (S. Typhimurium) and Salmonella Agona (S. Agona), specifically with attenuation of sopB, sopD, and pipD genes. Methods: Balb/c mice bearing CT26 tumours were inoculated with S. Typhimurium and S. Agona, both unattenuated and ΔsopBΔsopDΔpipD attenuated strains. Tumour volumes were monitored daily. Organs and blood were collected for plasma liver enzyme analysis and histopathology studies on testis, liver, kidneys and brain. Results: The ΔsopBΔsopDΔpipD S. Agona treated group showed improved inhibition of tumour growth with 51.11% tumour volume reduction compared to unattenuated S. Agona. The ΔsopBΔsopDΔpipD strains have also shown lesser systemic effects as observed in plasma and histopathological studies) compared to its unattenuated counterparts. Conclusion: The present study showed that ΔsopBΔsopDΔpipD S. Agona has a great potential to be utilised as tumour therapeutic agent as it exerts lesser systemic effect while having similar tumour inhibition capabilities as the well-studied S. Typhimurium strain.

Cytotoxic effects of commercial wheatgrass and fiber towards human acute promyelocytic leukemia cells [Hl60]

Cytotoxicity, the possible selective activity upon HL60 as well as the anti-proliferation effect of local health supplement wheatgrass and mixture of fibers were investigated in vitro using various cancerous cell line and normal blood cell culture. The IC[50] of wheatgrass-treated HL60 [17.5 +/- 1.1, 12.5 +/- 0.3, and 16 +/- 0.5 microgram/ml for 24, 48 and 72 h, respectively] and fibers-treated HL60 [86.0 +/- 5.5, 35.0 +/- 2.5, and 52.5 +/- 4.5 microgram/ml for 24, 48 and 72 h, respectively] showed that both extracts possessed optimum effect after 48 hours of treatment. No significant cytotoxic effect was observed on other type of cells. For trypan blue dye exclusion method, wheatgrass reduced the number of viable cells by 13.5% [ +/- 1.5], 47.1% [ +/- 3.6], and 64.9% [ +/- 2.7] after 24, 48 and 72 h exposure, respectively. Mixture of fibers reduced the number of viable cells by 36.4% [ +/- 2.3], 57.1% [ +/- 3.1], and 89.0% [ +/- 3.4] after 24, 48 and 72 h exposure, respectively, indicated that necrosis is also an alternative to the apoptotic mechanism of cell death. Annexin-V/propidium iodide staining revealed that both extracts induced apoptosis where early apoptosis had been detected concurrently with the reduction of percentage of cell viability. Cell cycle analysis revealed that in HL60, the percentage of apoptosis increased with time [wheatgrass: 16.0% +/- 2.4, 45.3% +/- 3.4 and 39.6% +/- 4.1; mixture of fibers: 14.6% +/- 1.8, 45.4% +/- 2.3 and 45.9% +/- 1.2] after exposure for 24, 48 and 72 h, respectively at the concentration of 100 microgram/ml and showed optimum effect at 48 hours. Thus, these health products can be a potential alternative supplement for leukaemia patients

Immunomodulatory effects of zerumbone isolated from roots of zingiber zerumbet

In this study, the immunomodulatory effects of zerumbone isolated from Zingiber zerumbet were investigated by evaluating the effects of this compound towards the lymphocytes proliferation [mice thymocytes, mice splenocytes and human human peripheral blood mononuclear cells, PBMC], cell cycle progression and cytokirie [interleukin 2 and 12] induction. Lymphocyte proliferation assay showed that zerumbone was able to activate mice thymocytes, splenocytes and PBMC at dosage dependent pattern where the best concentration was 7.5 micro g/mL. Flow cytometry analysis showed the highest population of PBMC entered into G2/M phase after treatment for 72 h with 7.5 micro g/mL zerumbone. The production of human interleukin-2 and human interleukin-12 cytokines in culture supernatant from zerumbone activated lymphocytes was prominently upregulated at 24 hour and decreased from 48 h to 72 h. The above results indicate that zerumbone can be used as immunomodulatory agent which can react toward the immune cell cytokine production in dosage dependent pattern