Apoptosis in Cancer Therapy

AnneMarie Woods

Introduction
Apoptosis is cell death. When cells do not go through apoptosis they
continue to divide causing tumors. These tumors can be malignant, meaning
dangerous. There are many different causes of cancer restricting the cells
from undergoing apoptosis. This paper takes a dip on the different cell
mutations causing these tumors and how apoptosis is involved in treatment.
What I Knew Before My Research
Before starting my search, I knew barely anything. I remember my
spark of interest in cancer came in sixth grade. It was Keyboarding and we
had to research different career options. Somewhere in there I found an
oncologist, the cancer doctor. Over the years I had forgotten all about
cancer and cancer research, up until Molecular Biology with Mr. Schratweiser
this year.
We were studying mitosis, the division of cells. We learned the
different stages of cell division. Apoptosis was included in this section. Cells
die or cease division when they do not pass one of the two checkpoints due
to mutations. This led to maybe a 15-minute quick lesson on how breast
cancer develops from cells not undergoing apoptosis. Fifteen minutes was all
it took to hook my attention.

I wasnt sure where to go from here. See, I had been going through a
very rough time. I was so overwhelmed I just didnt care about anything
anymore. I stopped completing school work. I slept through all my classes.
I had basically given up. All I knew was that I wanted to continue to research
cancer for my I-Search paper.
My Search
Most sophomore academy kids had three or four months to complete
all research and kept up with their deadlines. I did not have such a great
experience. Right before Spring Break in the middle of March I had to leave
school and did not come back until the very end of June. Since Ms. Graves,
the academy advisor and person assigning this paper, was not one of my
core teachers she was not given any information of where I had gone or why.
I basically fell off the face of the planet for a bit. During this time, I
completed limited school work, none of which was for Ms. Graves.
Upon my return I knew I had a lot of make-up work to complete. I was
very anxious about confronting my teachers for the first time in months,
especially Ms. Graves who knew nothing except that I wasnt in school. I was
blessed with understanding teachers. Ms. Graves reduced my work load
from one interview and six blog posts to no interview and four blog posts.
The four page I-Search paper was of course a must. The only problem was I
had one week to complete it. I continued to tell myself, You got this, but I
was sure not to overwhelm myself. I still wasnt in the greatest mental
health condition.

In class I began the search. I sat down, logged in, and was about to
break down. What on Earth was I doing? I pulled myself together and asked
Ms. Graves to help begin the search. She told me cancer was too broad and
gave me the topic of apoptosis and cancer treatment. I felt a weight off my
back and went to Google Scholar. I opened a paper from Oxford Journal and
began.
The paper wasnt too advanced, just many words I did not understand
(or know how to pronounce). I worked through class for about an hour and a
half. Then, I procrastinated and didnt do any more research until the night it
was due. I spent four hours straight taking notes and researching.
Thankfully I was interested and the time flew by. I went to post my research
to my blog and the site wasnt working. I started to get highly upset and my
anxiety almost burst over something so silly. I decided I would just have to
take the paper holding my notes to Ms. Graves, late as usual. However, I
spent a great deal of time find great information to write this paper, again
the night it was due.
Discoveries
In my first bit of research I basically started a glossary. I could go
through the whole list, but Im sure that would be a boring read. Relating to
the topic, I learned that oncogenic (tumor causing) mutations disrupt
apoptosis. These same mutations decrease treatment effectivity.
I continued to search starting with the different mutations interfering
with cell death. Internally apoptosis is automatically triggered from DNA

damage, telomere malfunctions, and oncogenic mutations. I was surprised

to see that telomeres had relation to cancer. I remembered learning about
telomeres in Biology. During DNA replication RNA begins the process by
attaching to a section of the DNA, but that section is not copied. Telomeres
are disposable buffers that are shortened during DNA replication instead of
the actual DNA. After so long of replication the telomeres and DNA becomes
too short to continue replication leading to cell death or becoming senescent
(inactive). The first mutation I learned was because of an abundance of
telomerase. The telomerase enzyme builds more telomeres. If telomeres
are continually made, then the cell will not undergo apoptosis leading to
tumor growth.
Oncogenic mutations are a bit more complicated. Oncogenes are
genes that turn cells into cancerous cells. During rodent cell
experimentation, the oncogene bcl-2 was one of the first oncogenes found
that promoted cell survival. Continuing to research these oncogenes, p53
was found. It was the first tumor suppressor gene found that promoted
apoptosis. If the body did not have enough p53, then that would lead to a
tumor. This gene was used in treatment to damage DNA and stop tumor
growth through apoptosis. The most common way to expose these tumors
to the p53 oncogene is through radiation. The problem with this treatment
was that the p53 promoted cell death not only in the cancerous cells but
normal, healthy cells too. This is why cancer patients have such severe side
effects such as nausea and hair loss.

There are also other oncogenes that promote apoptosis found through
experimenting an adenovirus in rodents. E1A is an oncoprotein that place
cells in the S phase of the cell cycle permitting virus replication. The
oncoprotein E1B works with E1A to promote the replication. Mutant mice
without E1B were found to have poor virus yield and created a E1Adependant phenotype that destroyed the viral DNA. This lead to the belief
that oncogenes such as E1A induce apoptosis while oncogenes like E1B work
to suppress it. Some cells grow exponentially or proliferate but are stable
because they undergo apoptosis through that promote apoptosis. Humans
have the oncogene c-myc that does this. However, other oncogenes, such
as IGF-1 found in humans, override apoptosis allowing these cells to continue
to proliferate and cause tumors.
Apoptosis has two different pathways. The first and more simple one is
from growth factors, cytokines, and DNA damage that signal death through
the mitochondria. The second pathway is through the inactive proenzyme
caspase that works as the engine of apoptotic cell death, according to
Scott Lowe and Athena Lin of Oxford Journal. The enzyme caspase causes
the inactivation or activation of substrates leading to the cascade of
signaling events permitting controlled demolition of the cell, as stated by
David R. McIlwain, Thorsten Berger, and Tak W. Mak of CHS Perspectives.
Because of these two pathways it is extremely rough to find the right
treatment. There is a high variation of requirements to induce apoptosis
using caspase for different cell death molecules. Also, there is cross talk

between these two pathways that affect treatment therapy. For example,
the caspase could signal apoptosis but the bcl-2 oncogene is supporting cell
survival. Thus, this creates a very complicated connection between
apoptosis and cancer treatment.

Citations
Enzyme Active Site and Substrate Specificity - Boundless Open Textbook.
(2016, May 25). Retrieved June 9, 2016, from
https://www.boundless.com/biology/textbooks/boundless-biologytextbook/metabolism-6/enzymes-72/enzyme-active-site-and-substratespecificity-350-11576/
Genetic Science Learning Center (2014, June 22) Are Telomeres The Key To
Aging And Cancer?. Learn.Genetics. Retrieved June 9, 2016, from
http://learn.genetics.utah.edu/content/chromosomes/telomeres
Lowe, S. W., & Lin, A. W. (1999, October 12). Apoptosis in cancer. Oxford
Journal. Retrieved June 8, 2016, from
https://carcin.oxfordjournals.org/content/21/3/485.full.
Mcllwain, D. R., Berger, T., & Mak, T. W. (2013). Caspase Functions in Cell
Death and Disease [Abstract]. Cold Spring Harb Perspective. Retrieved
June 9, 2016, from
http://m.cshperspectives.cshlp.org/content/5/4/a008656.abstract?
sid=9b81abb0-f7ac-4d03-a46a-05a0b03a66f6