Chapter 9, Problem 1DAA

RIPs as Cancer Drugs Researchers are taking a page from the structure-function relationship of RIPs in their quest for cancer treatments. The most toxic RIPs, remember, have one domain that interferes with ribosomes, and another that carries them into cells. Melissa Cheung and her colleagues incorporated a peptide that binds to skin cancer cells into the enzymatic part of an RIP, the E. coli Shiga-like toxin. The researchers created a new RIP that specifically kills .skin cancer cells, which are notoriously resistant to established therapies. Some of their results are shown in FIGURE 9.17.

FIGURE 9.17 Effect of an engineered RIP on cancer cells. The model on the left shows the enzyme portion of E. coli Shiga-like toxin engineered to carry a small sequence of amino acids (in blue) that targets skin cancer cells. (Red indicates the active site.) The graph on the right shows the effect of this engineered RIP on human cancer cells of the skin (); breast () liver (); and prostate ().

Which cells had the greatest response to an increase in concentration of the engineered RIP?

Summary Introduction

To determine: The type of cells that had the greatest response to an increase in the concentration of the engineered RIP.

Introduction: Ribosome-inactivating proteins (RIPs) inactivate the ribosomes and prevent protein synthesis in a cell. The toxic RIPs have a domain that makes them enter into the cell and another domain that interferes with the ribosome. They have antiviral and anticancer properties and are used to design drugs for HIV and cancer.

Answer to Problem 1DAA

Correct answer: The greatest response in the form of fall in cell’s survival percentage with an increase in the concentration of engineered RIP is seen in the skin cancer cells.

Explanation of Solution

As given in the problem statement, Researcher M and her colleagues incorporated a peptide into the enzymatic part of a RIP, the E. coli Shiga-like toxin. The peptide specifically binds to the skin cancer cells, and thus, the newly synthesized RIP kills the skin cancer cells.

Refer Fig. 9.17, “Effect of an engineered RIP on cancer cells”, in the textbook. The model shown on the left indicates a blue-colored enzyme region of E. coli Shiga-like toxin that is engineered to carry the peptide sequence specific for the skin cancer cells. The red color indicates the active site of RIP.

The graphical representation that is shown in Fig. 9.17 on the right side indicates the effect of the engineered RIP on different human cancer cells indicated by different colors and shapes. They include skin, breast, liver, and prostate cancer cells with red, blue, brown, and green color, respectively. The concentration of RIP (µg/liter) is plotted with the percentage of cell survival. As shown in the graph, as the concentration of RIP increases, there is a significant drop in the skin cancer cells percentage. It reaches to zero at RIP concentration of 10 µg/liter. In the case of the other cancer cells, there is lesser variability.

Thus, the greatest response in the form of fall in cell’s survival percentage with an increase in the concentration of engineered RIP is seen in the skin cancer cells.