Page 60 - D. Cancer biology

[D. Cancer biology-43]

Gossypol Suppresses Growth of Temozolomide-Resistant

Glioblastoma Tumor Spheres

Hee Yeon Kim¹˙²˙#, Byung Il Lee³˙⁴˙#, Ji Hoon Jeon¹, Dong Keon Kim¹, Seok-Gu Kang⁵, Jin-Kyoung Shim⁵,
Soo Youl Kim¹, Sang Won Kang², Hyonchol Jang¹˙⁴˙*

¹Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, Korea, ²Department of Life

Science, Ewha Womans University, Seoul 03760, Korea, ³Division of Precision Medicine, Research Institute, National
Cancer Center, Goyang 10408, Korea, ⁴Department of Cancer Biomedical Science, National Cancer Center
Graduate School of Cancer Science and Policy, Goyang 10408, Korea, ⁵Department of Neurosurgery, Brain Tumor

Center, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea

Temozolomide(TMZ) is the current first-line treatment for glioblastoma(GBM) patients but, because many patients

are resistant to it, there is an urgent need to develop antitumor agents to treat TMZ-resistant GBM. Gossypol, a
natural polyphenolic compound, has been studied as a monotherapy or combination therapy for the treatment of

GBM. The combination of gossypol and TMZ has been shown to inhibit GBM, but it is not clear yet whether gossypol
alone can suppress TMZ-resistant GBM. We find that gossypol suppresses the growth of TMZ-resistant GBM cells

in both tumor sphere and adherent culture conditions, with tumor spheres showing the greatest sensitivity.
Molecular docking and binding energy calculations show that gossypol has a similar a nity to the Bcl2 family of

proteins and several dehydrogenases. Gossypol reduces mitochondrial membrane potential and cellular ATP levels
before cell death, which suggests that gossypol inhibits several dehydrogenases in the cell’s metabolic pathway.

Treatment with a Bcl2 inhibitor does not fully explain the effect of gossypol on GBM. Overall, this study demonstrates
that gossypol can suppress TMZ-resistant GBM and will be helpful for the refinement of gossypol treatments by

elucidating some of the molecular mechanisms of gossypol in GBM.