Sains Malaysiana 53(8)(2024): 1981-1991

http://doi.org/10.17576/jsm-2024-5308-20

Cytotoxic Effect of Clinacanthus nutans Semi-purified Fraction (SF1) in Combination with Cisplatin against Human Cervical Cancer

(Kesan Sitotoksik Fraksi Separa Tulen (SF1) Clinacanthus nutans dalam Gabungan dengan Cisplatin terhadap Kanser Pangkal Rahim Manusia)

NUR FATIN NAJIHAH MARZUKI¹, YUSMAZURA ZAKARIA^1,*, MARYAM AZLAN¹ & NIK FAKHURUDDIN NIK HASSAN²

¹Biomedicine Programme, School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia

²Forensic Science Programme, School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia

Received: 15 October 2023/Accepted: 12 June 2024

Abstract

Cervical cancer is one of the most diagnosed malignancies in the world, and it is associated with HPV virus infection and invasion. A standard fraction from the medicinal plant Clinacanthus nutans was successfully separated, isolated, and identified as SF1 (semi-purified fraction). According to the previous study, SF1 has shown cytotoxic action against the cervical cancer cell line, SiHa. This study aims to further annotate the effect of SF1 in combination with cisplatin against SiHa to increase the selectivity of the anti-cancer treatment. The MTT assay was used to analyse the combination treatment's cytotoxicity, and its index value was calculated using the Chou-Talalay method. A cell survival test was conducted to evaluate the reproducibility of cancer cells after being treated. The combination treatment has enhanced cytotoxic action and inhibited SiHa’s cell proliferation the most (IC₅₀ value = 5.10 ± 0.86 μg/mL) compared to the individual cytotoxic activity of SF1 (IC₅₀ value = 9.60 ± 0.20 µg/mL) and cisplatin (IC₅₀ value = 3.60 ± 0.60 μg/mL). Simultaneously, the combination study has shown lesser cytotoxic activity towards normal cells, Vero (IC₅₀ value = 10.30 ± 3.10 μg/mL) compared to SiHa cells. The combination also showed an antagonism effect with CI values of 2.60 to 1.50 and fractional inhibition (Fa) of 0.50 to 0.90. The findings have demonstrated that in contrast with single-agent therapy, the treatment of SF1 and cisplatin in combination has increased the efficacy because it selectively targets cancer cells by antagonism action.

Keywords: Antagonism; Clinacanthus nutans; cisplatin; cytotoxicity; SiHa

Abstrak

Kanser pangkal rahim adalah salah satu kanser yang paling banyak didiagnosis di dunia dan ia dikaitkan dengan jangkitan dan pencerobohan virus HPV. Fraksi daripada tumbuhan ubatan Clinacanthus nutans berjaya dipisahkan, diasingkan dan dikenal pasti sebagai SF1 (fraksi separa – penulenan). SF1 telah menunjukkan tindakan sitotoksik terhadap titisan sel kanser pangkal rahim, SiHa menurut kajian terdahulu. Kajian kali ini bertujuan untuk menjelaskan lagi kesan SF1 dalam penggabungan dengan cisplatin terhadap SiHa untuk meningkatkan selektiviti untuk rawatan anti kanser. Asai MTT digunakan untuk menganalisis sitotoksisiti rawatan gabungan dan nilai indeks gabungannya dihitung menggunakan kaedah Chou-Talalay. Ujian kemandirian sel telah dijalankan untuk menilai kebolehulangan sel kanser selepas dirawat. Rawatan gabungan telah meningkatkan tindakan sitotoksik dan menghalang pembiakan sel SiHa paling banyak (nilai IC₅₀ = 5.10 ± 0.86 μg/mL) berbanding tindakan sitotoksik secara individu SF1 (nilai IC₅₀ = 9.60 ± 0.20 μg/mL) dan cisplatin (nilai IC₅₀ = 3.60 ± 0.60 μg/mL). Pada masa yang sama, kajian gabungan telah menunjukkan tindakan sitotoksik yang lebih rendah terhadap sel normal, Vero (nilai IC₅₀ = 10.30 ± 3.10 μg/mL) berbanding sel SiHa. Gabungan tersebut juga menunjukkan kesan antagonis dengan nilai CI 2.60 hingga 1.50 dengan perencatan pecahan (Fa) 0.50 hingga 0.90. Penemuan telah menunjukkan bahawa berbeza dengan terapi agen tunggal, rawatan gabungan SF1 dan cisplatin telah meningkatkan keberkesanan kerana ia secara selektif menyasarkan sel-sel kanser melalui tindakan antagonisme.

Kata kunci: Antagonisme; cisplatin; Clinacanthus nutans; SiHa; sitotoksiksiti

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*Corresponding author; email: yusmazura@usm.my