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

FARA VITANTRI  DIAH; NUZLI FAHDIA MAZFUFAH; WAWAIMULI AROZAL; MELVA LOUISA; SEPTELIA INAWATI WANANDI; SOMASUNDARAM ARUMUGAM; REMYA SREEDHAR; PUSPITA EKA WUYUNG

doi:10.22159/ijap.2025v17i1.52654

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 their markers: 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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