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Searching for metal compounds with promising antitumor activity and studies on their cellular targets and mechanism(s) of action
Bulgaria (AMSB) - Medical faculty of Sofia University, Sofia
Department of Pathology; Institute of Experimental Morphology, Pathology and Anthropology
Prof. Marin Ts. Alexandrov, DVM. PhD
Assoc. Prof. Radostina Alexandrova, PhD (Permanent position in IEMPAM ? BAS; Part time Ass
Type of Research Project
- Basic science
What is the background of the project?
The potential antineoplastic and antimicrobial activities of different metals and metal compounds have been under special interest during the recent years. The two main reasons for such interest are: 1) It has been found that the disturbed balance in the essential metal metabolism of mammals results an increased susceptibility to infections and malignancies; 2) Being involved in the regulation of some definite processes of the animal organisms, several metals are biological response modifiers.
The earliest reports on the therapeutic use of metals or metal-containing compounds in cancer and leukemia date from the sixteenth and nineteenth centuries. They were forgotten until the 1960s, when the anti-tumor activity of the inorganic complex cis-diammine-dichlorplatinum (II) (cis-[PtCl2(NH3)2](cis-DDP, cisplatin) was discovered. Today cisplatin is the world's leading anti-tumor drug for the chemotherapy of human cancer.
The discovery of the antitumor efficacy of cisplatin and some related platinum complexes has stimulated the search for other platinum and non-platinum metals with antineoplastic properties. Different metal complexes are found to be promising compounds for the design of new anticancer agents. An increasingly number of publications support the anticancer activity in vitro and in vivo of platinum, ruthenium, vanadium, gold, palladium, tin, gallium, titanium, lanthanides, zinc, copper, etc.
Studies of the anti-tumor activity of gold compounds were stimulated by several observations: 1) Patients treated with gold for rheumatoid arthritis (Chrisotherapy) had lower rates of malignancy than other patients; 2) Gold has been shown to have generally mild side effects when used clinically for patients with rheumatoid arthritis and the treatment can be conducted for long periods in many cases; 3) Gold in the +III oxidation state is isoelectronic with platinum (II) and forms similar square-planar complexes.
What is the aim of the project?
The aim of the project is to evaluate the effect of new metal compounds on viability and proliferation of cultured human and animal tumor cells and to attempt to identify their cellular targets and mechanism(s) of action.
What techniques and methods are used?
Various cell cultures will be used as experimental models in our investigations, incuding:
- permanent cell lines (as well as peimary cultures in sime of the experiments) established from some some of the most common and invasive tuman malignancies (glioblastoma multiforme, cancers of the breast, uterine cervix, colon, liver, lung, etc), some of which are characterized by multidrug resistance caused by overexpression of ATP-binding cassette (ABC) proteins, such as P-glycoprotein and MRP;
- animal cell lines extablished from retrovirus-induced transplantable tumors in chicken (cell line LSCC-SF-Mc29, hepatoma induced by the myelocytomatosis virus Mc29) and rat (LSR-SF-SR, sarcoma induced by Rous sarcoma virus strain Schmist-Ruppin). Both cell lines carry specific viral oncogenes ? v-myc (in the case of LSCC-SF-Mc29) and v-src (in the case of LSR-SF-SR). It is well known tha myc (c-myc, L-myc, N-myc) and src proto-oncogenes are involved in pathogenesis of a wide variety of malignancies in humans and animals;
- non-tumor human and animal (chicken, rat) cells (permanent cell lines and/or primary cultures) that will be used for comparative investigations.
The following metal compopunds will be examined in our study: Zn/Ag and Zn/Au complexes with Schiff bases; Complexes of non-steroidal antiinflamatory agents (isoxicam, meloxicam, piroxicam) with Zn(II), Cu(II), Co(II) and Ni(II); Ammonium vanadate.
What is the role of the student?
- The student will mainly observe
- The student will observe the practical experiments but will be highly involved in the analysis of the results
What are the tasks expected to be accomplished by the student?
The student will assist in the examination of the data compiled.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes Please contact the LORE
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a poster
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
No special skills and knowledge are required ? the education (first and second year) in Medical and Biological faculties is completely enough.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students
- 1. Abedulkadir Mahdi Abudalleh; Marin Alexandrov; Radostina Alexandrova. Ammonium vanadate decreases viability and proliferation activity of cultured virus-transformed rat sarcoma cells.Comptes rendus de l
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