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In vitro cytotoxicity of Phortress against colorectal cancer
Abhik Mukherjee1, Stewart Graham Martin
1Department of Oncology, University of Nottingham, City Hospital, Nottingham, NG5 1PB, UK.
Abstract:
Phortress is a novel benzothiazole compound with activity concentrated in certain breast, ovarian and renal cancer cell lines. Its anti-angiogenic effects are unknown. In this study, the in vitro anti-angiogenic effects of Phortress were screened for and results compared with two control drugs, paclitaxel and fumagillin. in vitro anti-angiogenic activity was examined by MTS assays, growth curves and clonogenic survival assays on human umbilical vein endothelial cells (HUVEC). In addition and as a comparator, effects were examined on MRCV fibroblasts and also the MCF7 breast cancer cell line, shown to be sensitive on the NCI60 panel and 3 colorectal cancer cell lines (HT29, SW480 and SW620) that were reportedly insensitive. Effects on endothelial tube differentiation were assessed by the Matrigel assay. Phortress had no effect on HUVEC and MRCV cell proliferation and survival. Unlike paclitaxel and fumagillin, Phortress did not inhibit endothelial tube differentiation. Phortress therefore exhibits no in vitro anti-angiogenic activity. As expected, Phortress was cytotoxic to MCF7 breast cancer cells, but unexpectedly, Phortress was also potent against colorectal cancer cells in clonogenic survival and cell growth (growth curves but not MTS assay) end-points. The efficacy of Phortress against colorectal cancer cells in the current study confirms that the spectrum of activity of Phortress may be wider than previously thought.
Insights
Phortress, a novel benzothiazole, shows no anti-angiogenic effects in vitro. However, it demonstrates unexpected potency against colorectal cancer cells, suggesting a broader therapeutic spectrum than previously known.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Phortress is a novel benzothiazole compound with known activity against breast, ovarian, and renal cancer cell lines.
- The anti-angiogenic effects of Phortress have not been previously investigated.
- Understanding Phortress's activity spectrum is crucial for its potential therapeutic applications.
Purpose of the Study:
- To screen the in vitro anti-angiogenic effects of Phortress.
- To compare Phortress's anti-angiogenic activity with paclitaxel and fumagillin.
- To evaluate Phortress's efficacy against various cancer cell lines, including those previously considered insensitive.
Main Methods:
- In vitro anti-angiogenic activity was assessed using MTS assays, growth curves, and clonogenic survival assays on human umbilical vein endothelial cells (HUVEC).
- Effects on endothelial tube differentiation were examined using the Matrigel assay.
- Cytotoxicity and proliferation were evaluated on MRCV fibroblasts, MCF7 breast cancer cells, and three colorectal cancer cell lines (HT29, SW480, SW620).
Main Results:
- Phortress exhibited no inhibitory effects on HUVEC or MRCV cell proliferation and survival.
- Phortress did not inhibit endothelial tube differentiation, unlike paclitaxel and fumagillin.
- Phortress was cytotoxic to MCF7 breast cancer cells and unexpectedly potent against colorectal cancer cell lines in clonogenic survival and cell growth assays.
Conclusions:
- Phortress displays no in vitro anti-angiogenic activity.
- The compound is cytotoxic to specific breast cancer cell lines.
- Phortress demonstrates significant efficacy against colorectal cancer cell lines, indicating a potentially broader spectrum of activity than initially recognized.
