Effect of 1,4-Napthoquinone Derivatives on Anti-proliferation and Apoptosis Induction in Skin and Lung Cancer Cells

Supajutha Poomsaard¹, Isara Sakdawattanakul¹, Nishsha Ackapronwong¹, Sukanda Innajak², Watcharaporn Poorahong², Ratchanok Pingaew³, Krerkwit Visitsakulchai⁴, Ramida Watanapokasin²

Affiliation : ¹ Medical Degree Program, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand, ² Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand, ³ Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok, Thailand, ⁴ Ratchaphiphat Hospital, Bangkok Medical service, Bangkok, Thailand

Background: Cancer is a major public health concern around the world. Nowadays, standard therapy in combination with targeted therapy are being used for cancer treatment, but these therapeutics show side effects or unwanted symptoms and high cost. 1,4- Napthoquinone and their derivatives were used in cancer research for a long time with high efficiency than some cancer drug. In the present study, the effect of a novel 1,4-napthoquinone, DL667 and DL666 on apoptosis induction in malignant melanoma, A375 cells and lung cancer, A549 cells, respectively were studied.
Objective: To investigate the effects of 1,4-napthoquinone derivatives, DL667 and DL66, on apoptosis induction in malignant melanoma, A375 and lung cancer, A549 cells, respectively.
Materials and Methods: Cell growth inhibition was determined by MTT assay. Apoptosis induction was via chromatin condensation or apoptotic bodies determined by Hoechst staining. In addition, changes in mitochondrial membrane potential (ΔΨm) were done by JC-1 staining.
Results: The results showed that DL667 inhibited cell growth in A375 with an IC50 at 11.2+0.419 μM in a concentration-dependent manner and DL666 inhibited cell growth of A549 cells at 200 μM. Hoechst staining assay revealed that both DL667 and DL666 could induce chromatin condensation and apoptotic bodies in A375 and A549 cells. In addition, the JC-1 staining showed that DL667 and DL666 decreased the ΔΨm, a marker event of early apoptosis via mitochondria, in A375 and A549 treated cells.
Conclusion: DL667 and DL666 showed anti-proliferation and apoptosis induction in A375 and A549 cells, respectively. Moreover, DL667 and DL666 induced chromatin condensation, apoptotic bodies and decreased the ΔΨm, resulting in apoptosis cell death induction. Our results suggested that the decrease of ΔΨm may be further developed as a model for study in other cancer cell lines. However, the underlying mechanisms of apoptosis induction associated with signaling should be further studied.

doi.org/10.35755/jmedassocthai.2022.S01.00015

Keywords : 1,4-Napthoquinone; Apoptosis; Chromatin condensation; Apoptotic bodies; Mitochondrial membrane potential

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