Showing papers by "Komal Raina published in 2018"

Nutraceuticals in prostate cancer therapeutic strategies and their neo-adjuvant use in diverse populations

Abstract: Prostate cancer (PCa) is the most frequently diagnosed malignancy and second leading cause of cancer mortality in American males. Notably, men of African descent in the United States and Caribbean have the highest PCa mortality rates compared to men with European ancestry. Although current therapeutics are quite potent and effective, disease resistance, progression to metastasis, therapy-associated toxicities and efficacy-related issues in diverse populations develop over time. Thus, non-toxic and efficacious therapeutic strategies are needed to address these major obstacles for the clinical treatment and management of PCa. In this regard, preclinical and population-based efficacy studies have shown the potential of natural non-toxic nutraceuticals as potent anti-PCa agents. Accordingly, the implementation of nutraceutical intervention and genetic testing in diverse populations might aid in the development and design of precision medicine strategies to reduce the burden of chemotherapy-associated toxicities, suppress disease resistance, and treat both localized and advanced PCa. Consequently, additional large-scale and inclusive clinical studies are required to fully assess efficacy and therapeutic limitations of these agents in PCa. This review discusses the most current clinical research on selected nutraceutical agents and their efficacy in the context of clinico-pathological outcomes and disease susceptibility in diverse PCa clinical and epidemiological studies.

Nintedanib inhibits growth of human prostate carcinoma cells by modulating both cell cycle and angiogenesis regulators.

Abstract: Prostate cancer (PCa) is the most common malignancy and second leading cause of cancer-related deaths in American men. Proliferating cells have higher need for nutrients and oxygen, triggering angiogenesis that plays a critical role in tumor growth, progression and metastasis. Consequently, immense focus has converged onto inhibitors of angiogenesis in cancer treatment, such as Nintedanib, which has shown exceptional antitumor activity via inhibiting cell proliferation and the resulting tumor growth, primarily due to its combined action on tumor cells, endothelial cells and pericytes. Accordingly, here we assessed both in vitro and in vivo efficacy of Nintedanib in PCa. The results showed that Nintedanib decreased cell viability in both androgen dependent- and -independent PCa cells, together with a decrease in cell motility and invasiveness. Nintedanib also reduced the expression of significant genes responsible for cell cycle progression. PCa PC3 xenograft-carrying nude mice treated with Nintedanib showed significantly decreased tumor volume and cell proliferation alongside diminished levels of pro-angiogenic molecules and blood vessel densities. In conclusion, we report that Nintedanib has strong efficacy against PCa in pre-clinical models via modulation of various pathways, and that it could be employed as a promising new strategy to manage PCa clinically.

Bitter melon juice exerts its efficacy against pancreatic cancer via targeting both bulk and cancer stem cells.

Abstract: Pancreatic cancer (PanC) is one of the deadliest malignancies worldwide and frontline treatment with gemcitabine becomes eventually ineffective due to increasing PanC resistance, suggesting additional approaches are needed to manage PanC. Recently, we have shown the efficacy of bitter melon juice (BMJ) against PanC cells, including those resistant to gemcitabine. As cancer stem cells (CSCs) are actively involved in PanC initiation, progression, relapse and drug-resistance, here we assessed BMJ ability in targeting pancreatic cancer-associated cancer stem cells (PanC-CSCs). We found BMJ efficacy against CD44+ /CD24+ /EpCAMhigh enriched PanC-CSCs in spheroid assays; BMJ also increased the sensitivity of gemcitabine-resistant PanC-CSCs. Exogenous addition of BMJ to PanC-CSC generated spheroids (not pre-exposed to BMJ) also significantly reduced spheroid number and size. Mechanistically, BMJ effects were associated with a decrease in the expression of genes and proteins involved in PanC-CSC renewal and proliferation. Specifically, immunofluorescence staining showed that BMJ decreases protein expression/nuclear localization of CSC-associated transcription factors SOX2, OCT4 and NANOG, and CSC marker CD44. Immunohistochemical analysis of MiaPaCa2 xenografts from BMJ treated animals also showed a significant decrease in the levels of CSC-associated transcription factors. Together, these results show BMJ potential in targeting PanC-CSC pool and associated regulatory pathways, suggesting the need for further investigation of its efficacy against PanC growth and progression including gemcitabine-resistant PanC.

Mechanisms and Drug Targets for Pancreatic Cancer Chemoprevention.

Abstract: Background Pancreatic cancer management remains a major challenge to society. Poor prognosis results in dismal patient survival rates and quality of life post chemo/radiation therapies. Although progress has been made in drug development for targeting pancreatic cancer, accompanying issues of drug resistance renders it futile. While intake of fruits and vegetables in routine diets has been linked to reduced risk of pancreatic cancer, a wide variety of natural agents are being evaluated as adjuvant therapies in combination with frontline chemotherapeutics in pancreatic cancer clinical trials. Objective This review highlights the emerging area of cancer chemoprevention with natural/ dietary compounds serving as novel agents possessing strong anticancer properties; these are pleiotropic agents targeting multiple pathways with minimal toxicity in normal tissue. Methods We employed extensive literature search and considered all the relevant information presented in a concise, well-balanced and structured format. Results Completed and ongoing human studies with natural agents have shown surprisingly successful rates for regulating pancreatic carcinogenesis. Combinatorial therapies with synthetic, approved drugs and natural agents not only improved the patient response rates, but also helped in overcoming drug resistance and inducing chemosensitivity to the resistant tumors, as opposed to monotherapies for pancreatic cancer chemoprevention. Conclusion The current review focuses on the available chemotherapeutic drugs and their limitations, and moves on to discuss the wide realm of chemopreventive efficacy that the natural agents have to offer. It discusses the underlying mechanisms of action and available information, from extensive literature analysis, to highlight the novelty of these agents for their antitumor effects against pancreatic cancer.