A hemagglutinin isolated from Northeast China black beans induced mitochondrial dysfunction and apoptosis in colorectal cancer cells

Abstract

Incidence of colorectal cancer is closely related with the lifestyle, especially the dietary habits of patients. Epidemiological researches have demonstrated a negative correlation between legume consumption and colorectal cancer incidence. Lectins/hemagglutinins are a type of carbohydrate binding proteins which are abundantly stored in legumes. Their eminent pH-stability allows them to survive digestion and remain active in the intestine where they may have direct contact with colorectal tumors. It is therefore interesting to explore the direct interaction between lectins/hemagglutinins and colorectal cancer. In the present research, we reported a detailed research on the interaction between a hemagglutinin isolated from an edible legume with two colorectal cancer cell lines. This hemagglutinin (NCBBH) was found to first bind to tumor cell membrane as early as 30min post treatment and was gradually transported inside the cytoplasm within 3h, with some of it localized in the Golgi apparatus and some in the lysosomes. After its entrance, the hemagglutinin induced aggregation of the Golgi apparatus, which in turn adversely affected the transportation of protein from endoplasmic reticulum (ER) to the Golgi apparatus, resulting in protein accumulation in ER and ER stress. The hemagglutinin-treated cells also manifested severe mitochondrial malformation and membrane depolarization, accompanied by obvious apoptosis characteristics, like chromatin condensation, phosphatidylserine exposure and caspase activation. Collectively, our results indicate that the hemaggltuinin could successfully enter the cytoplasm of colorectal cancer cells and adversely affect their growth, providing a mechanism in support of the application of edible legumes to the prevention and treatment of colorectal cancer.

A Ribonuclease Isolated from Wild Ganoderma Lucidum Suppressed Autophagy and Triggered Apoptosis in Colorectal Cancer Cells

“…Cells were collected after treatment with 1 μM GLR for 24 h and rinsed with PBS before fixation in 2.5% glutaraldehyde for 1 h. TEM Samples were prepared by using the method that has been previously reported ( Dan et al, 2016 ). The prepared sample sections were successively stained with uranyl acetate and lead citrate before final examination with a transmission electron microscope (Hitachi H-7700).…”

Lectins, Interconnecting Proteins with Biotechnological/Pharmacological and Therapeutic Applications

“…The ability of lectins to inhibit the growth of cancer cells in vitro is well documented in the literature and some examples are listed in Table 1 [13–21, 23–25, 27–29, 89, 111, 178–181]. In addition, to reduce cell proliferation, lectins may interact with receptors and other molecules present in cell surface and/or cytosol, activating cell death pathways.…”

“…A remarkable example is the lectin from Northeast China black beans, which was reported to bind HCT116 (colorectal carcinoma) cell membrane and was found in the Golgi apparatus and lysosomes within 3 h after treatment. Authors also described that this lectin caused aggregation of Golgi complex, protein accumulation in the endoplasmic reticulum, mitochondrial malformation, and membrane depolarization [29]. …”

A Novel Molecular Model of Plant Lectin-Induced Programmed Cell Death in Cancer

“…Furthermore, via activation of IKK-NF-κB-cyclooxygenase (COX)-2, SHP-2-MEK-1-ERK, SHP-2-Ras-ERK signaling, ConA was reported inhibit survival in tumor cell model. 35,36) Under the treatment of PCL, apoptosis was induced with the activation of caspase-3,-8,-9.…”