Investigation of potential inhibitory effects of natural compounds from Melissa officinalis L. in drug-resistant non-small cell lung carcinoma
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Tarih
2022
Yazarlar
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Cilt Başlığı
Yayıncı
Adana Alparslan Türkeş Bilim ve Teknoloji Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Kanser tedavisinde yeni nesil ilaçların geliştirilmesi ve cerrahideki yenilikler hastaların yaşam beklentisini önemli ölçüde uzatmıştır. Ancak tüm bu gelişmelere rağmen akciğer kanseri tedavisindeki temel engel, tedavide kullanılan kemoterapötik ilaçlara karşı içsel veya dışsal direnç nedeniyle hastalığın zamanla tekrarlamasıdır. Kemorezistansın gelişmesiyle başa çıkmak için alternatif yöntemlere ve yeni terapötiklere ihtiyaç vardır. Doğal bitki bileşikleri, düşük sitotoksisiteleri ve insan vücudunda iyi tolere edilebilirlikleri nedeniyle kanser dahil birçok hastalığın tedavisinde uzun yıllardır kullanılan ilaç etken maddelerinin elde edilmesinde kullanılabilecek çok önemli kaynaklardır. Türkiye'de yaygın olarak yetiştirilen ve limon otu olarak bilinen Lamiaceae familyasından iyi bilinen bir tıbbi bitki olan Melissa officinalis L.'nin küçük hücreli dışı akciğer kanseri hücre hattı A549 ve erlotinib dirençli A549 alt hücre hattı ile ilaç hariç paralel koşullarda geliştirilmiş parental alt hücre hattı üzerindeki antikanserojenik etkileri değerlendirilmiştir. Çalışmamızda Melissa officinalis L. bitkisinin yaprak kısımlarından farklı çözgenlerle dört farklı ekstrakt elde edilmiştir. Tüm ekstraktların farklı A549 alt hücre hatları üzerindeki sitotoksik etkileri MTT hücre canlılık testi ile belirlenmiştir. Bu analizde farklı çözgenlerle üretilen özütlerin herbirinin tüm alt hücre hatlarında etkili oldukları görülmekle birlikte aralarında önemli farklılıklar bulunmadığı görülmüştür. Bundan dolayı bitkideki tüm madde gruplarını içeren total metanolik fraksiyon ile çalışma devam ettirilmiştir. Daha sonra total metanolik yaprak fraksiyonunun tüm alt hücre hatlarında hücre migrasyonu üzerindeki etkileri yara iyileştirme testi ile, hücrelerin koloni oluşturma ve tümörijenik kapasiteleri üzerindeki etkileri yumuşak agar koloni oluşturma testi ile belirlenmiştir. Son olarak aynı yaprak fraksiyonunu kanser hücre döngüsü ilerleyişi üzerindeki etkileri de akış sitometrisi analizi ile belirlenmiştir. Analiz sonuçlarına göre, total metanolik yaprak fraksiyonunun artan konsantrasyonun, konsantrasyona bağlı biçimde hücre canlılığını azalttığı ve üç alt hücre hattında da göç kapasitesini ve koloni oluşumunu önlediği, ayrıca DNA replikasyonunun gerçekleştiği S fazındaki hücre popülasyonunu, kontrol bileşiğine maruz bırakılan hücrelere göre azalttığı belirlenmiştir. Bu bulgular ışığında Melissa officinalis L. bitkisinin küçük hücreli dışı akciğer kanseri tedavisi için yeni bir alternatif terapötik kaynağı olabileceği düşünülmektedir. Anahtar Kelimeler: Melissa officinalis L., doğal bileşikler, A549, anti-kanser , ilaç direnci
In cancer treatment, the development of new generation drugs and innovations in surgery have significantly extended the life expectancy of patients. However, despite all these developments, the main obstacle in the treatment of lung cancer is the recurrence of the disease over time due to intrinsic or extrinsic resistance to the chemotherapeutic drugs used in the treatment. Alternative methods and new therapeutics are needed to cope with the development of chemoresistance. Due to their low cytotoxicity and good tolerability in the human body, natural plant compounds are very important sources that can be used to obtain drug active ingredients that have been used in the treatment of many diseases, including cancer, for many years. In this study, the anticarcinogenic effects of Melissa officinalis L., a well-known medicinal plant from the Lamiaceae family, widely grown in Turkey and known as lemongrass, on the non-small cell lung cancer cell line A549 and the erlotinib resistant A549 sub-cell line and its parallel parental sub cell-line were evaluated. In our study, four different extracts were obtained from the leaf parts of Melissa officinalis L. plant with different solvents. The cytotoxic effects of these extracts on each cell line were determined by MTT cell viability analysis. As a result, although each type of extract was cytotoxic on each sub-cell line, there was no significant difference between their inhibitory intensities. The remainder of the study was then continued with the total methanolic fraction, which includes all of the substance groups in the plant leaf. Afterwards, the effects of this extract on the migration of different sub-cell lines were determined by the wound healing assay, whereas tumorigenic capacities were determined by the soft agar colony formation test. Finally the effects of the total methanolic extract on the cell cycle progression were determined by flow cytometry analysis. According to the results, increasing concentration of total MeOH extract of M. officinalis L. decreases cell viability in a concentration dependent manner and prevents both migration capacity and colony formation in all types of sub-cell lines. A decrease was observed in the S-phase cell populations, where DNA replication takes place, compared to cells exposed to control in all three sub-cell lines. In the light of these findings, it is thought that Melissa officinalis L. plant may represent an alternative source of novel therapeutic compounds for treatment of non-small cell lung cancer. Keywords: Melissa officinalis L. , natural compounds, A549, anticancer , drug resistance
In cancer treatment, the development of new generation drugs and innovations in surgery have significantly extended the life expectancy of patients. However, despite all these developments, the main obstacle in the treatment of lung cancer is the recurrence of the disease over time due to intrinsic or extrinsic resistance to the chemotherapeutic drugs used in the treatment. Alternative methods and new therapeutics are needed to cope with the development of chemoresistance. Due to their low cytotoxicity and good tolerability in the human body, natural plant compounds are very important sources that can be used to obtain drug active ingredients that have been used in the treatment of many diseases, including cancer, for many years. In this study, the anticarcinogenic effects of Melissa officinalis L., a well-known medicinal plant from the Lamiaceae family, widely grown in Turkey and known as lemongrass, on the non-small cell lung cancer cell line A549 and the erlotinib resistant A549 sub-cell line and its parallel parental sub cell-line were evaluated. In our study, four different extracts were obtained from the leaf parts of Melissa officinalis L. plant with different solvents. The cytotoxic effects of these extracts on each cell line were determined by MTT cell viability analysis. As a result, although each type of extract was cytotoxic on each sub-cell line, there was no significant difference between their inhibitory intensities. The remainder of the study was then continued with the total methanolic fraction, which includes all of the substance groups in the plant leaf. Afterwards, the effects of this extract on the migration of different sub-cell lines were determined by the wound healing assay, whereas tumorigenic capacities were determined by the soft agar colony formation test. Finally the effects of the total methanolic extract on the cell cycle progression were determined by flow cytometry analysis. According to the results, increasing concentration of total MeOH extract of M. officinalis L. decreases cell viability in a concentration dependent manner and prevents both migration capacity and colony formation in all types of sub-cell lines. A decrease was observed in the S-phase cell populations, where DNA replication takes place, compared to cells exposed to control in all three sub-cell lines. In the light of these findings, it is thought that Melissa officinalis L. plant may represent an alternative source of novel therapeutic compounds for treatment of non-small cell lung cancer. Keywords: Melissa officinalis L. , natural compounds, A549, anticancer , drug resistance
Açıklama
Fen Bilimleri Enstitüsü, Biyomühendislik Ana Bilim Dalı
Anahtar Kelimeler
Biyomühendislik, Bioengineering
