For those that want more clinical information, here is a quick write up I did on it.

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Intracellular Pathways Influenced by Ivermectin

• 1. Inhibition of the Wnt/β-Catenin Signaling Pathway: The Wnt/β-catenin pathway plays a critical role in cell proliferation and differentiation. Aberrant activation of this pathway is associated with various cancers. Ivermectin has been shown to inhibit this pathway, leading to reduced tumor growth and metastasis.
• 2. Modulation of mTOR Pathway: The mammalian target of rapamycin (mTOR) is a key regulator of cell growth and metabolism. Ivermectin can inhibit the mTOR pathway, which is often overactive in cancer cells, thereby reducing cell proliferation and promoting apoptosis.
• 3. Induction of Autophagy and Apoptosis: Ivermectin can induce autophagy, a process where cells degrade and recycle their components. This autophagic response can lead to apoptosis, particularly in cancer cells, where cellular stress and damage are prevalent. By promoting cell death in this manner, ivermectin can effectively reduce cancer cell viability.

Inhibition of Glycolysis

Cancer cells often rely on glycolysis for energy production, a phenomenon known as the Warburg effect. Ivermectin has been shown to interfere with glycolysis by:

• 1. Targeting Key Glycolytic Enzymes: Ivermectin can inhibit enzymes involved in the glycolytic pathway, such as hexokinase and phosphofructokinase. By disrupting these enzymes, ivermectin impairs the energy production of cancer cells, making it difficult for them to sustain rapid growth.
• 2. Downregulation of Glucose Transporters: Ivermectin has been observed to reduce the expression of glucose transporters (GLUTs) on the cell surface. This reduction limits glucose uptake, further restricting the glycolytic capacity of cancer cells and leading to energy depletion.

Overcoming Chemoresistance: Inhibition of P-glycoprotein (P-gp) Pumps

Chemoresistance is a significant challenge in cancer treatment, often mediated by P-glycoprotein (P-gp) pumps. These pumps actively expel chemotherapeutic agents from cancer cells, reducing their efficacy. Ivermectin's ability to inhibit P-gp pumps is crucial for overcoming this resistance:

• 1. Direct Inhibition of P-gp Activity: Ivermectin directly interacts with P-gp, reducing its drug efflux capacity. This inhibition allows chemotherapeutic agents to remain inside the cells at therapeutic concentrations, enhancing their cytotoxic effects.
• 2. Restoration of Drug Sensitivity: By inhibiting P-gp, ivermectin can restore sensitivity to previously resistant cancer drugs. This property is particularly valuable in cases where cancer cells have developed resistance to multiple drugs, often a result of overexpression of P-gp.
• 3. Synergistic Effects with Chemotherapeutic Agents: Ivermectin has been shown to work synergistically with certain chemotherapeutic agents, such as doxorubicin and vincristine, enhancing their efficacy by preventing drug expulsion from cancer cells. This combination therapy approach could lead to more effective treatment regimens with potentially lower doses of chemotherapeutic agents, reducing toxicity and side effects.

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Questions?

• if you want more information on this topic, phytochemicals, their pharmacokinetic properties, other intracellular routes of cancer etc. Or you just want some research on a particular subject around medicine done, Just let me know, I would be happy to help.