Abstract
Olivacine is an alkaloid-containing pyridocarbazole structure. It is isolated from the bark of the evergreen timber tree, Aspidosperma olivaceum. Its well-documented anticancer activity led to the synthesis of new derivatives, which are semisynthetic and fully synthetic pyridocarbazoles. This study aimed to evaluate the potential antineoplastic activity of four newly synthesized olivacine derivatives. Multidrug resistance is a common phenomenon causing failure in the chemotherapy of many tumors. It is mainly related to increased function of P-glycoprotein, an efflux pump removing cytostatic out of the cells. The cell lines used in the study were colorectal carcinoma cell lines: LoVo (doxorubicin-sensitive) and LoVo/DX (doxorubicin-resistant). The NHDF cell line was used to assess cell viability. First, the cells were incubated with olivacine derivatives. In the next step, the following assays were performed: DCF-DA assay, MTT assay, rhodamine 123 assay, detection of apoptosis, proliferation inhibition-mitotic index. The tested compounds showed higher antineoplastic potential and lower toxicity than the reference compound ellipticine. The results indicate that the new olivacine derivatives are good candidates for future anticancer drugs.
Highlights
Chemotherapy is one of the most common methods of systemic treatment of neoplasms used nowadays in therapy
On the other hand, when considering new substances with antineoplastic potential, screening examinations on well-defined cell lines (e.g., tumors derived from ovaries, brain, intestine, lungs, kidneys, blood, skin, prostate) are carried out [2]
The reference compound ellipticine impacted Rh-123 accumulation only in the LoVo cell line in the 1–5 μM range. This may indicate the usefulness of these derivatives as they were more effective in P-gp inhibition and cytostatic activity than ellipticine
Summary
Chemotherapy is one of the most common methods of systemic treatment of neoplasms used nowadays in therapy. It is applied either in monotherapy or more often in polytherapy because it is quite effective in reducing tumor mass and growth in many types of neoplasms. Chemotherapy is combined with other local methods of treatment, including removing/reducing tumor mass with surgery or radiotherapy [1]. Pyridocarbazoles are a group of well-examined alkaloids with proven anticancer activity. One of their representatives is ellipticine (5,11-dimethyl-6H-pyrido [4,3-b]carbazole), discovered in the 1960s
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