Chemopreventive Agents
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
The potential for berberine to act as a cancer chemopreventive agent is based on the observation that it suppresses the growth of a wide variety of tumor cell types in culture including melanoma, breast, pancreatic, prostate, mouth, gastric, hepatoma, glioblastoma, neuroblastoma, and leukemia cells. In experiments of this type, the potency of berberine is in the order of 10–100 μM (IC50), depending on the cell type and duration of treatment. The mechanism of action for growth inhibition appears to be based on inducing cell-cycle arrest at the G1 or G2/M phases and by causing apoptosis. It also produces endoplasmic reticulum stress and autophagy in some tumor cell types. Animal studies have also shown that it can suppress chemical-induced carcinogenesis, clastogenesis, tumor promotion, tumor invasion, and angiogenesis. It has also been shown to act as a radiosensitizer toward tumor cells but not normal cells.
Nutritional Regulation of the Growth Plate
Crystal D. Karakochuk, Kyly C. Whitfield, Tim J. Green, Klaus Kraemer in The Biology of the First 1,000 Days, 2017
Longitudinal bone growth is driven by chondrogenesis, and the proliferation and hypertrophic differentiation of chondrocytes at the growth plate cartilage. The growth plate is regulated by complex interactions between different endocrine systems, epigenetic mechanisms, and intracellular signaling pathways. Nutrition plays an important role in modulating these multiple regulatory mechanisms of the growth plate, thereby only permitting rapid linear growth when the organism is able to take in plentiful nutrients. As children grow and continue to increase in height, the growth plate gradually ages (becomes senescent), leading to functional and structural declines of the growth plate and a decrease in growth velocity, until growth stops and adult height is attained. The temporary inhibition of bone growth during childhood may also slow down aging of the growth plate, which may help explain the spike in growth rate when growth inhibition is resolved, a clinical phenomenon also known as catch-up growth.
Preclinical and clinical development of new progesterone receptor antagonists with high receptor specificity for breast cancer treatment
A. R. Genazzani in Hormone Replacement Therapy and Cancer, 2020
In intact control animals, progressive tumor growth was observed, whereas ovariectomy caused a complete tumor regression in 90% of the animals. A dose of 0.5 mg/kg of the progesterone antagonist ZK 230211 administered subcutaneously led to an inhibition of tumor growth, although this was not statistically significant. A maximal statistically significant growth inhibition was achieved with doses ≥ 2 mg/kg (Figure 4). In the group treated with 2 mg/kg, 50% of the animals showed complete tumor regression. Higher doses of ZK 230211 (5 and 10 mg/kg) resulted in tumor growth inhibition comparable to that with the dose of 2 mg/kg. Onapristone, a pure progesterone receptor antagonist, also showed a growth-inhibitory effect, but with no statistical significance at the dose used (5 mg/kg). Taken together, in the DMBA-induced mammary tumor model in the rat, ZK 230211 completely suppressed tumor growth in intact animals. At equal doses, the newer investigational drug ZK 230211 was distinctly more potent than onapristone.
Bacterial death from treatment with fluoroquinolones and other lethal stressors
Published in Expert Review of Anti-infective Therapy, 2021
We begin by distinguishing growth inhibition from killing (Figure 1). Growth inhibition is assayed with the stressor present, as with determination of minimal inhibitory concentration (MIC); killing is measured as bacterial survival after stressor removal. Some killing, an irreversible process, may occur during growth-inhibition measurements, but in those measurements killing cannot be distinguished from growth inhibition, which is reversible. This consideration is important, because bacteriostasis assays, such as the efficiency-of-plating test, are commonly interpreted in terms of killing. The two processes are also mechanistically distinct – mutations and chemicals exist that affect only killing. For example, during norfloxacin treatment a deficiency in catalase has no effect on MIC, but the deficiency lowers survival by 10–20 fold [7].
Ethanol-based proliposome delivery systems of paclitaxel for in vitro application against brain cancer cells
Published in Journal of Liposome Research, 2018
Mohammad Najlah, Mohit Jain, Ka-Wai Wan, Waqar Ahmed, Mohamed Albed Alhnan, David A. Phoenix, Kevin M. G. Taylor, Abdelbary Elhissi
SVG-P12 cells showed less sensitivity to paclitaxel and paclitaxel-loaded liposomes than U87-MG cells. This may be due to the reason that the rate at which tumor cells are killed is dependent on their growth curve. Growth curve analysis of the cell lines plays a crucial role in understanding the cell proliferation and effect of anti-tumor agents on them. U87-MG cells reached high confluency (80–90%) in 2 days while SVG-P12 cells achieved the similar confluency in 4–5 days, for further sub-culturing of the cells. The growth and division of normal cells such as SVG-P12, in tissue culture conditions, are similar to that of U87-MG cells. However, the growth rate of normal cells decreases once they cover the bottom of the culture flask and remain as a monolayer. Growth inhibition may be caused by the exhaustion of growth factors in the medium. On the other hand, glioma cells continue to grow until they overlap with surrounding cells and form clumps. This may be because they are unresponsive to the signals that cause the cessation of growth and division of their normal counterparts. This might explain the rapid decrease in the viability of U87-MG cells as compared to that of SVG-P12 cells when treated with paclitaxel and liposome formulations (Karp, 2010).
Drug delivery targets and strategies to address mast cell diseases
Published in Expert Opinion on Drug Delivery, 2023
Clayton H. Rische, Ariel H. Thames, Rebecca A. Krier-Burris, Jeremy A. O’Sullivan, Bruce S. Bochner, Evan A. Scott
Siglecs have also been shown to be viable targets for the selective elimination of mast cells (Figure 3) [193,194]. Furthermore, in addition to systemic mastocytosis and mast cell malignancies, mast cell reduction, or elimination may be useful when treating other conditions such as chronic urticaria. In addition, several Siglecs have demonstrated endocytic properties, which may be exploited for selective drug payload delivery to mast cells [57,193–195]. Because of the scarcity of natural killer (NK) cells in most tissue compartments containing mast cells, it is expected that antibody-dependent cellular phagocytosis (ADCP) via macrophages predominates over antibody-dependent cellular cytotoxicity (ADCC) via NK cells [196,197]. Alternative strategies for reduction/elimination have also relied on growth inhibition or other cytotoxic mechanisms.
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