published results in 2020<\/a> showing that DDX5 helps support the cancer\u2019s malignant growth. DDX5 belongs to a family of RNA helicases, enzymes that unwind RNA molecules to begin a process allowing for various cellular functions to occur.
The 2020 paper reported that blocking DDX5 activity in SCLC cells via genetic manipulation reduces oxidative phosphorylation. This compromises the mitochondria \u2014 the powerhouse of the cells \u2014 and they die.
\u201cThe mitochondria go bad, and you have defective oxidative phosphorylation as well as defective cellular respiration,\u201d said co-author Subhadeep Das, a postdoctoral scientist in biochemistry.
The researchers found that Supinoxin acts on DDX5 to reduce oxidative phosphorylation, Das noted. Oxidative phosphorylation is an essential part of the cellular respiration process that fuels virtually all biological and physical activity. Cellular respiration generates adenosine triphosphate (ATP), the energy-carrying molecule that fuels cellular activity.
Research dating back a century led scientists to believe that cancer cells depend solely on glycolysis to generate ATP. In the last decade, however, new evidence has emerged that some cancer cells draw upon oxidative phosphorylation to generate ATP.
\u201cIt is still commonly thought that cancer cells rely on energy only by using the glycolysis pathway, but that turns out not to be true for all cancer types,\u201d Tran explained. In cancer cells that depend predominantly on glycolysis, sugar is taken in and burned for energy without the end product of that reaction going through oxidative phosphorylation to obtain ATP in large amounts.
\u201cSome types of cancer do use oxidative phosphorylation, and if they don\u2019t have any energy, they can\u2019t grow,\u201d Tran said. \u201cThere is still an open question because we don\u2019t know precisely how DDX5 is playing a role in that process of generating ATP.\u201d
Tran, an RNA biologist, joined the Purdue faculty in 2009. Her early work at Purdue focused on using baker\u2019s yeast as a model system for understanding RNA biology.
\u201cWe did a lot of work on an RNA helicase in that model system,\u201d Tran said. \u201cWe found out what it does in a cell, but we also knew that its human counterpart had connections to cancer, and we didn\u2019t understand why.\u201d That led Tran to begin researching SCLC in 2018.
\u201cWe wanted not only to understand what that RNA helicase counterpart does in human cells, but if it is connected to promoting cancer growth and metastasis, can we stop it? Is there some way to identify a new chemotherapeutic that could be used to treat cancer types?\u201d
Tran touts the potential for studying RNA helicase inhibitors like Supinoxin not only as cancer treatments but also as lab tools to learn how helicases work and what they do. DDX5 belongs to a family consisting of 40 RNA helicases.
A better understanding of RNA biology could lead to new targets for human disease treatment, Tran noted. Chemotherapies often target the cycle that cells undergo to grow and divide.
\u201cRNA in general hasn\u2019t been on people\u2019s radar. It has precedence, I just don\u2019t think it\u2019s generally acknowledged,\u201d she said. Elzey agreed that looking further into RNA biology could yield new clinical cancer treatments targeting the DDX family of proteins. \u201cI\u2019m looking forward to expanding our model, refining it and answering more difficult questions with it,\u201d he said.
This research was funded by the Purdue Institute for Cancer Research and the National Institutes of Health.<\/p>\n","protected":false},"excerpt":{"rendered":"Purdue University scientists led by co-principal investigators in the Colleges of Agriculture and Veterinary Medicine have identified the Supinoxin small-molecule drug as a possible new therapy for small-cell lung cancer (SCLC).<\/p>\n","protected":false},"author":7,"featured_media":29764,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[36,11],"tags":[744,123,317,8,811,150],"class_list":["post-30368","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-cancer","category-research","tag-cancer-research","tag-cpb","tag-discovery","tag-faculty","tag-pvm-report","tag-research"],"acf":[],"_links":{"self":[{"href":"https:\/\/vet.purdue.edu\/news\/wp-json\/wp\/v2\/posts\/30368","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/vet.purdue.edu\/news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/vet.purdue.edu\/news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/vet.purdue.edu\/news\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/vet.purdue.edu\/news\/wp-json\/wp\/v2\/comments?post=30368"}],"version-history":[{"count":2,"href":"https:\/\/vet.purdue.edu\/news\/wp-json\/wp\/v2\/posts\/30368\/revisions"}],"predecessor-version":[{"id":31818,"href":"https:\/\/vet.purdue.edu\/news\/wp-json\/wp\/v2\/posts\/30368\/revisions\/31818"}],"wp:attachment":[{"href":"https:\/\/vet.purdue.edu\/news\/wp-json\/wp\/v2\/media?parent=30368"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/vet.purdue.edu\/news\/wp-json\/wp\/v2\/categories?post=30368"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/vet.purdue.edu\/news\/wp-json\/wp\/v2\/tags?post=30368"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}