Sains Malaysiana 49(5)(2020): 1107-1114

http://dx.doi.org/10.17576/jsm-2020-4905-15

Gallic Acid and Methyl Gallate Enhance Antiproliferative Effect of Cisplatin on Cervical Cancer (HeLa) Cells

(Asid Galik dan Metil Galat Mempertingkat Kesan Antiproliferatif Cisplatin ke atas Sel Kanser Serviks (HeLa))

NORLIDA MAMAT^{1, 2}*, HASMAH ABDULLAH², HERMIZI HAPIDIN² & NOOR FATMAWATI MOKHTAR³

¹Faculty of Health Sciences, Gong Badak Campus, Universiti Sultan Zainal Abidin, 21300 Kuala Nerus, Terengganu Darul Iman, Malaysia

²School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan Darul Naim, Malaysia

³Institute for Research in Molecular Medicine (INFORMM), Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan Darul Naim, Malaysia

Received: 23 April 2019/Accepted: 15 January 2020

ABSTRACT

Cervical cancer is the fourth most common cancer-related death affecting women. The drug resistance, toxicities and undesired side effects become the major limitation in cisplatin-based chemotherapy. Gallic acid and methyl gallate are the most abundance phenolic compounds that are widely distributed in plants. This study was conducted to evaluate the antioxidant and antiproliferative activity of gallic acid and methyl gallate and their synergistic effects in combination with cisplatin towards cervical cancer (HeLa) cells. The antioxidant activity of gallic acid and methyl gallate was measured by using 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging assay. Antiproliferative activity of gallic acid, methyl gallate and cisplatin on HeLa and NIH/ 3T3 cells was determined using MTT assay. The effect of gallic acid and methyl gallate combined with cisplatin were then determined by CompuSyn software. Gallic acid and methyl gallate showed strong antioxidant activity with EC₅₀ value of 18.23 µM and 19.39 µM, respectively. The IC₅₀ of gallic acid, methyl gallate and cisplatin on HeLa cells were 13.44 µg/mL, 16.55 µg/mL, and 8.04 µg/mL whereas in NIH/3T3 cells were 32.90 µg/mL, 35.70 µg/mL, and 6.57 µg/mL. Cisplatin combined with fixed concentration of gallic acid and methyl gallate could inhibit the proliferation of HeLa cells greater than cisplatin alone. Interestingly, gallic acid and methyl gallate in combination with cisplatin at the concentration of 0.51-4.02 µg/mL have shown synergistic effects. Therefore, our study suggested that gallic acid and methyl gallate in combination with cisplatin have the potential to be developed as chemotherapeutic agents for cervical cancer.

Keywords: Antioxidant activity; antiproliferative activity; gallic acid; methyl gallate; synergistic effect

ABSTRAK

Kanser serviks merupakan kanser keempat yang paling kerap dihidapi dalam kalangan wanita. Faktor kerintangan, kesan toksik dan kesan sampingan yang tidak diingini mengehadkan penggunaan cisplatin dalam rawatan kanser. Asid galik dan metil galat merupakan fenolik yang paling banyak ditemui dalam tumbuhan. Kajian ini dijalankan untuk menilai aktiviti antioksidan dan akiviti antiproliferatif asid galik dan metil galat dan kesan sinergi kombinasinya dengan cisplatin ke atas sel kanser serviks (HeLa). Aktiviti antioksidan asid galik dan metil galat ditentukan dengan asai hapus-sisa radikal bebas DPPH. Manakala aktiviti antiproliferatif ke atas sel HeLa dan NIH/3T3 ditentukan melalui asai MTT. Kesan kombinasi antara asid galik dan metil galat dengan cisplatin ditentukan dengan perisian CompuSyn. Asid galik dan metil galat menunjukkan aktiviti antioksidan yang kuat dengan nilai EC₅₀ masing-masing adalah 18.23 µM dan 19.39 µM. IC_50, bagi asid galik, metil galat dan cisplatin ke atas sel HeLa pula adalah 13.44 µg/mL, 16.55 µg/mL dan 8.04 µg/mL manakala pada sel NIH/ 3T3 adalah 32.90 µg/mL, 35.70 µg/mL dan 6.57 µg/mL. Kombinasi antara cisplatin dan asid galik serta metil galat pada kepekatan tertentu berupaya merencat pertumbuhan sel HeLa dengan lebih cekap berbanding dengan rawatan cisplatin sahaja. Kombinasi asid galik dan metil galat dengan cisplatin pada kepekatan 0.51-4.02 µg/mL juga telah menunjukkan kesan sinergi. Oleh itu, kombinasi asid galik dan metil galat dengan cisplatin berpotensi untuk dibangunkan sebagai agen rawatan kemoterapi untuk kanser serviks.

Kata kunci: Aktiviti antioksidan; aktiviti antiproliferatif; asid galik; kesan sinergi; metil galat

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*Corresponding author; email: norlida@unisza.edu.my