The incidence of melanoma is steadily increasing worldwide. Melanoma is the most lethal skin cancer, and new therapeutic methods are being sought. Our research aimed to investigate the cytotoxic and antiproliferative effects of betulinic acid in vitro, used alone and in combination with taxanes (paclitaxel, docetaxel) in four melanoma cell lines. Isobolographic analysis allowed us to assess the interactions between these compounds. Betulinic acid had no cytotoxic effect on normal human keratinocyte HaCaT cells; the amount of LDH released by them was significantly lower compared to melanoma cell lines. The present study shows that betulinic acid significantly inhibits the growth of melanoma cell lines in vitro. The IC50 values of betulinic acid ranged from 2.21 µM to 15.94 µM against the four melanoma lines. Co-treatment of betulinic acid with paclitaxel or docetaxel generated desirable drug–drug interactions, such as an additive and additive with a tendency to synergy interactions.
Introduction. Neoplastic diseases are a common cause of death, especially in developed countries. Various methods are used in cancer therapy including natural substances. Terpenes and terpenoids play a special role, including betulin and betulinic acid with the pentacyclic structure of lupane. They have a wide range of pharmacological activity, among which anti-cancer activity attracts the greatest attention. Abbreviated description of the state of knowledge. The review discusses the pharmacological effects of betulin and its derivatives on tumours, and focuses on the potential of its application in the treatment of melanoma. The review study also presents future prospects for the use of this natural substance. Betulin and its derivatives have the ability to influence the processes of apoptosis, angiogenesis and autophagy. Additionally, they have the ability to sensitize, increasing the sensitivity to commonly used methods of cancer treatment. To-date, numerous studies have been carried out on the synthesis of betulinic acid derivatives, which would show greater polarity and activity compared to the starting compound. Due to their greater bioavailability, the modified compounds showed a stronger anti-tumour effect. Conclusion.The results of the above-mentioned studies confirm the anti-cancer properties of betulin. Regarding melanoma, betulin shows significant therapeutic efficacy. This gives new perspectives for the treatment of the most dangerous skin cancer.
Wprowadzenie i cel pracy. Diagnozę nowotworu dostają miliony ludzi na świecie, a ich liczba nieustannie rośnie. Aby pomóc w zwalczeniu tej śmiercionośnej choroby, naukowcy od lat pracują nad znalezieniem coraz to lepszych leków. Źródłem wielu z nich jest natura. Do takich związków należą taksany -substancje pochodzące z wyciągu z cisu, które wykazują działanie przeciwnowotworowe. Opis stanu wiedzy. Do grupy taksanów należą: paklitaksel, docetaksel i kabazytaksel. Są to leki cytostatyczne, działające poprzez stabilizację tubuliny. Istnieją dwie teorie wyjaśniające śmierć komórek po stosowaniu taksanów: jedna z nich to zatrzymanie komórek w mitozie, a druga to śmierć w wyniku aktywacji punktów kontrolnych w odpowiedzi na nieprawidłową segregację chromosomów wśród komórek, które przeszły nieprawidłową mitozę bądź uległy poślizgowi mitotycznemu. Śmierć następuje w mechanizmie apoptozy. Naukowcy opracowują różne sposoby zwiększenia biodostępności leków, by uzyskać lepsze efekty terapeutyczne oraz stosować lek w jak najniższej możliwej dawce, tak aby zminimalizować ryzyko efektów ubocznych. Taksany są powszechnie stosowane w terapii wielu nowotworów. Leczy się nimi np. pacjentów z rakiem piersi, jajnika, prostaty, żołądka, niedrobnokomórkowym rakiem płuc. W pracy omówione zostały te terapie z uwzględnieniem najnowszych doniesień naukowych. Dodatkowo szczególnie dokładnie opisana została możliwość leczenia taksanami najgroźniejszego nowotworu skóry -czerniaka, w tereapii którego dotychczas leki te nie były rutynowo stosowane. Podsumowanie. Badania naukowe rozwijają wiedzę o działaniu taksanów i potwierdzają ich właściwości antynowotworowe ratujące życie coraz to większej grupy pacjentów onkologicznych.
Introduction and objective: Migraine constitutes the main reason for acute and recurrent headache among children globally. It is a primary headache syndrome that affects from 3 up to 10% of paediatric population. The frequency of migraine increases with age up to puberty. The aim of this study is to systemize recent knowledge about migraine in children. The information used in the presented analysis was obtained by searching academic research databases: Google Scholar and PubMed. An abbreviated description of the state of knowledge: The exact pathogenesis of migraine remains unknown, but involvement of nervous system, cardiovascular system, genetic predisposition and environmental factors are considered in the development of disease. Symptoms of migraine vary between individuals and can be wide-ranging. They may resemble disorders such as tension headache, cluster headache, epilepsy, brain tumour or ischemic stroke. The diagnostic process is based on anamnesis, and may therefore be challenging in children because of difficulties related to communication. Symptom-relieving therapy of migraine is well-established in contrast to pharmacological prophylactic treatment which is not sufficiently evidence-based. Summary: Migraine remains a global problem in the paediatric population. The condition is associated not only with physical pain, but also it leads to many long-term complications such as emotional problems and social disruption. Lack of safe and effective preventive medical therapies is a driving factor to improve trials of migraine treatment in the future.
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