Sains Malaysiana 52(12)(2023): 3823-3840
http://doi.org/10.17576/jsm-2023-5212-15
Pyranocycloartobiloxanthone
A Suppressed Metastasis Ovarian Cancer Cells via S Phase Cell Cycle Arrest and
Apoptosis
(Piranosikloartobilozanton A Menindas Metastasis Sel Kanser Ovari melalui Hentian Kitaran Sel Fasa
S dan Apoptosis)
MASHITOH
ABD RAHMAN1, NAJIHAH MOHD HASHIM1,2,* &
IDRIS ADEWALE AHMED3
1Department of Pharmaceutical Chemistry, Faculty of
Pharmacy, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
2Centre for Natural Products Research and Drug
Discovery (CENAR), Universiti Malaya, 50603 Kuala Lumpur, Malaysia
3Department of Biotechnology, Faculty of Applied
Science, Lincoln University, Kelana Jaya 47301 Petaling Jaya, Selangor,
Malaysia
Received: 14 April 2023/Accepted: 11 December 2023
Abstract
Ovarian cancer is a deadly
disease with a poor prognosis, highlighting the urgent need for novel
therapeutic alternatives. Pyranocycloartobiloxanthone A (PA), an exceptional
xanthone compound has garnered attention due to its diverse medicinal
properties. This study aimed to investigate the anticancer properties of PA on
metastatic ovarian cancer SKOV-3 cells. Cytotoxicity was evaluated using an MTT
assay, while apoptotic mechanisms were determined using AO/PI double staining,
annexin V-fluorescein isothiocyanate, multiple cytotoxicity-3, reactive oxygen
species (ROS) production, caspases, real-time PCR, western blot, human
apoptosis protein profile array and cell cycle analysis. PA inhibited SKOV-3
cell proliferation in a time-dependent manner, with an IC50 of 7.0 ±
0.5 µg/mL and a selectivity index of 13.2 after 72 h of treatment. PA induced
apoptosis through the intrinsic apoptotic pathway and arrested the cell cycle
at the S phase. PA stimulated ROS production and disrupted the mitochondrial
membrane potential, releasing cytochrome c from mitochondria to the
cytosol. Additionally, results from human apoptotic protein profile indicated
that 21 proteins were upregulated while 22 proteins were downregulated,
including Bcl-2, survivin, and HSP70. These findings suggest that PA has the
potential as a lead molecule in the development of a chemotherapy drug for
ovarian cancer. However, further research is necessary to evaluate the safety
and efficacy of PA in preclinical and clinical settings.
Keywords: Apoptosis; Artocarpus obtusus; cell
cycle; ovarian cancer; pyranocycloartobiloxanthone A
Abstrak
Kanser ovari adalah penyakit yang membawa maut dengan
prognosis yang kurang baik, menunjukkan keperluan yang mendesak untuk terapi
alternatif yang novel. Piranosikloartobilozanton A (PA), sebatian zanton yang
luar biasa telah menarik perhatian kerana sifat perubatannya yang pelbagai.
Penyelidikan ini bertujuan untuk mengkaji sifat antikanser PA ke atas sel
kanser ovari metastatis SKOV-3. Sitotoksisiti dinilai menggunakan asai MTT,
manakala mekanisme apoptosis ditentukan menggunakan pewarnaan berganda AO/PI,
annexin V-fluoresein isotiosianat, pelbagai sitotoksisiti-3, pengeluaran
spesies oksigen reaktif (ROS), caspases, masa nyata PCR, pemblotan
western, profil protein apoptosis manusia dan analisis kitaran sel. PA merencat
proliferasi sel SKOV-3 bergantung kepada masa dengan IC50 7.0 ± 0.5
µg/mL dan indeks selektiviti sebanyak 13.2 selepas 72 jam rawatan. PA aruhan
apoptosis melalui laluan apoptosis intrinsik dan menahan kitaran sel pada fasa
S. PA merangsang pengeluaran ROS dan mengganggu potensi membran mitokondria,
melepaskan sitokrom c daripada mitokondria ke sitosol. Selain itu, hasil
daripada profil protein apoptosis manusia menunjukkan bahawa pengawalaturan 21
protein telah meningkat manakala 22 protein telah menurun termasuk Bcl-2,
survivin dan HSP70. Penemuan ini mencadangkan bahawa PA mempunyai potensi
sebagai molekul utama dalam membangunkan dadah kemoterapi untuk kanser ovari.
Walau bagaimanapun, kajian lanjut adalah perlu untuk menilai keselamatan dan
keberkesanan PA dalam konteks praklinikal dan klinikal.
Kata kunci: Apoptosis; Artocarpus obtusus; kanser ovari; kitaran sel; piranosikloartobilozanton A
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*Corresponding author; email: najihahmh@um.edu.my
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