ADDITIVE CYTOTOXIC EFFECT OF CISPLATIN AND ANDROGRAPHIS PANICULATA EXTRACT THROUGH THE MODULATION OF APOPTOTIC MARKERS, CYCLIN-D AND VEGF EXPRESSIONS IN SKOV3 OVARIAN CANCER CELL LINE

Authors

  • FARA VITANTRI DIAH Doctoral Program in Medical Sciences, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia. Department of Obstetrics and Gynecology, Syarif Hidayatullah State Islamic University Jakarta, Jakarta, Indonesia https://orcid.org/0009-0009-3761-5045
  • NUZLI FAHDIA MAZFUFAH Stem Cell and Tissue Engineering Research Center, Indonesia Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia https://orcid.org/0000-0002-9020-831X
  • WAWAIMULI AROZAL Department of Pharmacology and Therapeutics, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia https://orcid.org/0000-0002-8071-9001
  • MELVA LOUISA Department of Pharmacology and Therapeutics, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia https://orcid.org/0000-0002-9451-0380
  • SEPTELIA INAWATI WANANDI Department of Biochemistry and Molecular Biology, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
  • SOMASUNDARAM ARUMUGAM Department of Pharmacology and Toxicolgy, National Institute of Pharmaceutical Education and Research (NIPER), Kolkata, India https://orcid.org/0000-0002-2096-2552
  • REMYA SREEDHAR Department of Pharmacy, Sister Nivedita University, Kolkata, India
  • PUSPITA EKA WUYUNG Department of Pharmacy, Sister Nivedita University, Kolkata, India

DOI:

https://doi.org/10.22159/ijap.2025v17i1.52654

Keywords:

Andrographolide, Apoptosis, Angiogenesis, Cycle cell, Ovarian cancer, SKOV3

Abstract

Objective: This study aims to investigate the possibility of additive cytotoxic effects of cisplatin and Andrographis paniculate (Burm.f.) Nees(AP) via apoptotic, cell cycle and angiogenesis pathways.

Methods: CC50 cisplatin, AP and Andrographolide (AG) were determined by the cell viability of SKOV3 after its exposure to these substances. SKOV3 cells were then divided into 6 experimental groups: one negativecontrol group, one with CC50 cisplatin alone, and three where CC50 was combined with CC50 AP, ½CC50 AP, and 1.5CC50 AP respectively. The additive cytotoxic effect of cisplatin with AP or AG was evaluated through the modulation of several pathways via qRT-PCR of theirmarkers: apoptotic pathways indicated by Bax, BCL2, Caspase 3 and Caspase 9 expression; cell cycle indicated by Cyclin-D expression; angiogenesis pathways by VEGF expression.

Results: Cisplatin reduces cell viability to 54%, 37% when combined with AG, and 30%, 23% and 20% with ½CC50 AP, CC50 AP and 1.5CC50 AP respectively. AG and AP extract decreases SKOV3 cell viability in a dose-dependent manner. Cisplatin combined with AP showed a statistically significant increase in BAX, Caspase 3, Caspase 9 expression, and a decrease in BCL2 which indicated synergy in apoptotic pathways. The best result was seen in cisplatin combined with ½CC50 AP. A decrease in Cyclin D and VEGF was seen in all groups, the best seen in ½CC50 AP and CC50 AP respectively, showing optimal cell cycle arrest and anti-angiogenesis properties when cisplatin is combined with AP extract.

Conclusion: Combining cisplatin with AP extract enhanced cell cycle arrest, apoptosis, and anti-angiogenesis properties.

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Published

27-11-2024

How to Cite

DIAH, F. V. ., MAZFUFAH, N. F., AROZAL, W., LOUISA, M., WANANDI, S. I., ARUMUGAM, S., SREEDHAR, R., & WUYUNG, P. E. (2024). ADDITIVE CYTOTOXIC EFFECT OF CISPLATIN AND ANDROGRAPHIS PANICULATA EXTRACT THROUGH THE MODULATION OF APOPTOTIC MARKERS, CYCLIN-D AND VEGF EXPRESSIONS IN SKOV3 OVARIAN CANCER CELL LINE. International Journal of Applied Pharmaceutics, 17(1). https://doi.org/10.22159/ijap.2025v17i1.52654

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