Apigenin is an edible plant-derived flavonoid that shows modest anti-tumor activities in vitro and in vivo. Apigenin treatment resulted in cell growth arrest and apoptosis in various types of tumors by modulating several signaling pathways. In the present study, we evaluated interactions between apigenin and ABT-263 in colon cancer cells. We observed a synergistic effect between apigenin and ABT-263 on apoptosis of colon cancer cells. ABT-263 alone induced limited cell death while upregulating expression of Mcl-1, a potential mechanism for the acquired resistance to ABT-263. The presence of apigenin antagonized ABT-263-induced Mcl-1 upregulation and dramatically enhanced ABT-263-induced cell death. Meanwhile, apigenin suppressed AKT and ERK activation. Inactivation of either AKT or ERK by lentivirus-transduced shRNA or treatment with specific small molecule inhibitors of these pathways enhanced ABT-263-induced cell death, mirroring the effect of apigenin. Moreover, the combination response was associated with upregulation of Bim and activation of Bax. Downregulation of Bax eliminated the synergistic effect of apigenin and ABT-263 on cell death. Xenograft studies in SCID mice showed that the combined treatment with apigenin and ABT-263 inhibited tumor growth by up to 70% without obvious adverse effects, while either agent only inhibited around 30%. Our results demonstrate a novel strategy to enhance ABT-263 induced anti-tumor activity in human colon cancer cells by apigenin via inhibition of the Mcl-1, AKT and ERK pro-survival regulators.

The bone morphogenic protein (BMP) antagonist Gremlin-1 is a biologically significant regulator known for its crucial role in tissue differentiation and embryonic development. Nevertheless, it has been reported that Gremlin-1 can exhibit its function through BMP dependent and independent pathways. Gremlin-1 has also been reported to be involved in organ fibrosis, which has been correlated to the development of other diseases, such as renal inflammation and diabetic nephropathy. Based on growing evidence, Gremlin-1 has recently been implicated in the initiation and progression of different types of cancers. Further, it contributes to the stemness state of cancer cells. Herein, we explore the recent findings on the role of Gremlin-1 in various cancer types, including breast, cervical, colorectal, and gastric cancers, as well as glioblastomas. Additionally, we highlighted the impact of Gremlin-1 on cellular processes and signaling pathways involved in carcinogenesis. Therefore, it was suggested that Gremlin-1 might be a promising prognostic biomarker and therapeutic target in cancers.

Gastrointestinal bleeding accounts for a drastic negative impact on the quality of the patients’ lives as it requires multiple diagnostic and therapeutic interventions to identify the source of the bleeding. Small bowel bleeding is the least common cause of gastrointestinal bleeding. However, it is responsible for the majority of complaints from patients with persisting or recurring bleeding where the primary source of bleeding cannot be identified despite investigation. A somatostatin analog known as octreotide is among the medical treatment modalities currently used to manage small bowel bleeding. This medication helps control symptoms of gastrointestinal bleeding by augmenting platelet aggregation, decreasing splanchnic blood flow, and antagonizing angiogenesis. In this review article, we will highlight the clinical efficacy of octreotide in small bowel bleeding and its subsequent effect on morbidity and mortality.

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia state (HHS) are two life-threatening metabolic complications of diabetes that significantly increase mortality and morbidity. Despite major advances, reaching a uniform consensus regarding the diagnostic criteria and treatment of both conditions has been challenging. A significant overlap between these two extremes of the hyperglycemic crisis spectrum poses an additional hurdle. It has well been noted that a complete biochemical and clinical patient evaluation with timely diagnosis and treatment is vital for symptom resolution. Worldwide, there is a lack of large-scale studies that help define how hyperglycemic crises should be managed. This article will provide a comprehensive review of the pathophysiology, diagnosis, and management of DKA-HHS overlap.

Apigenin is an edible plant-derived flavonoid showing anti-tumor activities in vitro and in vivo. Pretreatment with apigenin resulted in cell growth arrest and/or apoptosis in various types of tumors via modulating multiple cell signaling pathways. In the present study, we evaluated interactions between apigenin and ABT263 in multiple colon cancer cell lines. We found that apigenin enhanced ABT263-induced apoptosis in colon cancer cells in a time- and dose-dependent manner. ABT263 alone only resulted in limited cell killing in association with upregulation of Mcl-1, a potential mechanism for acquired ABT263 resistance. Apigenin antagonized ABT263-induced Mcl-1 expression and dramatically enhanced ABT263-induced cell death. Apigenin also suppressed AKT and ERK activation. Inactivation of either AKT or ERK pathway by lentivirus-transduced shRNA or specific small molecule inhibitors synergized with ABT263 to induce cell death, reflecting that AKT and ERK pathways are apigenin targets. Moreover, the synergism between ABT263 and apigenin was associated with the upregulation of Bim and subsequent activation of Bax. Xenograft studies with HCT116 cells in SCID mice showed that the combination treatment with apigenin and ABT263 inhibited tumor growth up to 70% without obvious adverse effects, while either agent alone showed only about 30% inhibition. Collectively, our findings demonstrate a novel and effective strategy to treat colon cancer by combination of ABT263 and apigenin. The combined effect is mediated by apigenin downregulation of Mcl-1, Akt and ERK activities. Citation Format: Huanjie Shao, Kai Jing, Esraa Mahmoud, Xianjun Fang, Chunrong Yu. Modulation of AKT, ERK and Mcl-1 by apigenin sensitizes colon cancer cells to anti-tumor activities of ABT263. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3290. doi:10.1158/1538-7445.AM2013-3290