PMID- 34736967 OWN - NLM STAT- MEDLINE DCOM- 20220302 LR - 20220302 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 912 DP - 2021 Dec 5 TI - Selective therapeutic benefit of X-rays and inhibitors of EGFR, PI3K/mTOR, and Bcl-2 in breast, lung, and cervical cancer cells. PG - 174612 LID - S0014-2999(21)00768-8 [pii] LID - 10.1016/j.ejphar.2021.174612 [doi] AB - Cancer continues to be a growing burden, especially in the resource limited regions of the world, and more effective and affordable therapies are highly desirable. In this study, the effect of X-ray irradiation and four inhibitors, viz. those against epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), mammalian target of rapamycin (mTOR) and B-cell lymphoma 2 (Bcl-2) was evaluated in lung, breast, and cervical cancer cell lines, including normal cell lines to determine and compare the potential therapeutic benefit of these treatment modalities. A clonogenic survival assay was used to determine the radiosensitivity and cytotoxicity of inhibitors of EGFR, PI3K/mTOR, and Bcl-2 in the cell lines. From the data, the equivalent dose at which 50% of the cell populations were killed, for cancer and normal cells, was used to determine the relative cellular sensitivity to X-ray irradiation and inhibitor treatment. It was found that breast cancer cell lines were more sensitive to X-ray irradiation, whilst cervical and lung cancer cell lines were more sensitive to EGFR and PI3K/mTOR inhibitor therapy. These data suggest that patients with breast cancer possessing similar characteristics to MDA-MB-231 and MCF-7 cells may derive therapeutic benefit from X-ray irradiation, whilst EGFR and PI3K/mTOR inhibitor therapy may potentially benefit cancer patients possessing cancers similar to HeLa and A549 cells. CI - Copyright (c) 2021. Published by Elsevier B.V. FAU - Hamid, Mogammad Baaghith AU - Hamid MB AD - Division of Radiobiology, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa. FAU - Serafin, Antonio Mendes AU - Serafin AM AD - Division of Radiobiology, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa. Electronic address: antoniomserafin@gmail.com. FAU - Akudugu, John Mbabuni AU - Akudugu JM AD - Division of Radiobiology, Department of Medical Imaging and Clinical Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa. Electronic address: jakudugu@sun.ac.za. LA - eng PT - Journal Article DEP - 20211102 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Aniline Compounds) RN - 0 (BCL2 protein, human) RN - 0 (Imidazoles) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Quinazolines) RN - 0 (Quinolines) RN - 0 (Sulfonamides) RN - 0 (Tyrphostins) RN - 170449-18-0 (RTKI cpd) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - RUJ6Z9Y0DT (dactolisib) RN - XKJ5VVK2WD (navitoclax) SB - IM MH - Aniline Compounds/pharmacology MH - Breast Neoplasms/metabolism/*therapy MH - Cell Line MH - Cell Survival/drug effects MH - ErbB Receptors/antagonists & inhibitors MH - Female MH - Humans MH - Imidazoles/pharmacology MH - Lung Neoplasms/metabolism/*therapy MH - Phosphatidylinositol 3-Kinase/metabolism MH - Phosphoinositide-3 Kinase Inhibitors/*pharmacology MH - Proto-Oncogene Proteins c-bcl-2/*antagonists & inhibitors MH - Quinazolines/pharmacology MH - Quinolines/pharmacology MH - Radiation Tolerance/drug effects MH - Sulfonamides/pharmacology MH - TOR Serine-Threonine Kinases/*antagonists & inhibitors MH - Tyrphostins/pharmacology MH - Uterine Cervical Neoplasms/metabolism/*therapy MH - X-Rays OTO - NOTNLM OT - ABT-263 OT - AG-1478 OT - Breast cancer OT - Cervical cancer OT - Inhibitor therapy OT - Lung cancer OT - NVP-BEZ235 OT - Radiotherapy EDAT- 2021/11/06 06:00 MHDA- 2022/03/03 06:00 CRDT- 2021/11/05 05:48 PHST- 2021/05/31 00:00 [received] PHST- 2021/10/26 00:00 [revised] PHST- 2021/10/29 00:00 [accepted] PHST- 2021/11/06 06:00 [pubmed] PHST- 2022/03/03 06:00 [medline] PHST- 2021/11/05 05:48 [entrez] AID - S0014-2999(21)00768-8 [pii] AID - 10.1016/j.ejphar.2021.174612 [doi] PST - ppublish SO - Eur J Pharmacol. 2021 Dec 5;912:174612. doi: 10.1016/j.ejphar.2021.174612. Epub 2021 Nov 2.