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Tumor inhibition by titanocene complexes: influence upon two xenografted human lung carcinomas
Abstract:
The influence of the organometallic complexes titanocene dichloride, titanocene dibromide, titanocene bis(hydrogenmaleinate), and titanocene bis(p-aminothiophenolate) bis(hydrochloride) on the development of a lung adenocarcinoma and a small cell lung carcinoma, both xenografted into athymic mice, was investigated in the present study. The tumors were growing s.c., and the substances administered i.p. as fivefold injections according to a Q2D X 5 (every 2 days X 5) or a Q3D X 5 schedule. In the case of lung adenocarcinoma, titanocene complexes inhibited tumor growth by more than 50% resulting in treated/control values of 20%-50%. The suppression remained stable beyond the end of the treatment period. In the case of small cell lung carcinoma, only those Q2D X 5 schedules, which corresponded to LD10 doses, effected considerable and stable growth inhibition to less than 50% of control values. Titanocene dichloride showed the greatest activity against both human tumors, followed by the p-aminothiophenolate, and hydrogenmaleinate derivatives.
Insights
Titanocene complexes significantly inhibited lung adenocarcinoma and small cell lung carcinoma growth in mice. Titanocene dichloride demonstrated the strongest anti-tumor activity in this preclinical study.
Area of Science:
- Oncology
- Medicinal Chemistry
- Pharmacology
Background:
- Lung cancer, including adenocarcinoma and small cell carcinoma, remains a significant global health challenge.
- Organometallic complexes, particularly titanocene derivatives, have shown potential as anti-cancer agents.
- Investigating novel therapeutic strategies is crucial for improving lung cancer treatment outcomes.
Purpose of the Study:
- To evaluate the anti-tumor efficacy of four titanocene complexes against human lung adenocarcinoma and small cell lung carcinoma xenografts in athymic mice.
- To compare the effectiveness of different dosing schedules (Q2D x 5 and Q3D x 5) and identify the most active titanocene derivative.
Main Methods:
- Human lung adenocarcinoma and small cell lung carcinoma xenografts were established in athymic mice.
- Titanocene dichloride, dibromide, bis(hydrogenmaleinate), and bis(p-aminothiophenolate) bis(hydrochloride) were administered intraperitoneally.
- Injections were given on Q2D x 5 (every 2 days x 5) or Q3D x 5 schedules, with some doses corresponding to LD10.
Main Results:
- Titanocene complexes inhibited lung adenocarcinoma growth by over 50%, with treated/control values ranging from 20%-50%.
- Tumor growth suppression in adenocarcinoma was stable post-treatment.
- For small cell lung carcinoma, only Q2D x 5 schedules at LD10 doses achieved significant and stable growth inhibition (<50% of control).
- Titanocene dichloride exhibited the highest activity against both tumor types, followed by p-aminothiophenolate and hydrogenmaleinate derivatives.
Conclusions:
- Titanocene complexes demonstrate significant anti-tumor activity against human lung cancer xenografts.
- Titanocene dichloride is a promising candidate for further investigation in lung cancer therapy.
- Dosing schedule and specific titanocene derivative influence therapeutic efficacy.