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Synergistic Cytotoxic Effect from Combination of Wedelolactone and Cisplatin in HeLa Cell Line: A Novel Finding
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-09-22 , DOI: 10.2147/dddt.s261321 Sadia Sarwar 1, 2 , Jun Qing Yu 1 , Humaira Nadeem 3 , Fazlul Huq 1
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-09-22 , DOI: 10.2147/dddt.s261321 Sadia Sarwar 1, 2 , Jun Qing Yu 1 , Humaira Nadeem 3 , Fazlul Huq 1
Affiliation
Context and Objective: Cisplatin is a platinum drug in current clinical use for the treatment of cervical cancer. However, drug toxicity and resistance are its two major limitations. The aim of this investigation was to test the cytotoxic activity of potential phytochemicals alone and in combination with cisplatin in cervical cancer cells.
Methods: In this study, cytotoxicity of phytochemicals including wedelolactone (WDL), betulinic acid (BA) and epigallocatechin gallate (EGCG) was investigated in human cervical cancer cell line HeLa through 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay. Combined drug action resulting from the combination of cisplatin with WDL and BA was investigated in the same cell line through median effect principle. The combination index (CI) was taken as a measure of combined drug action.
Results: BA resulted in synergistic outcome when co-administered with cisplatin at 0/0 time; (bolus administration) while administration of either drug (cisplatin or BA) four hours before the other (0/4 or 4/0) resulted in antagonistic action. WDL, on the other hand, was found out to be synergistic at any of the applied sequence of drug administration (0/0, 0/4 or 4/0).
Discussion and Conclusion: This is the first study reporting cytotoxic activity of WDL in HeLa cells either as single agent or in combination with cisplatin. These results support the idea that sequential combination of cisplatin with WDL and BA may work effectively in cervical cancer cells.
Keywords: HeLa, wedelolactone; WDL, betulinic acid; BA, MTT reduction assay, combination index; CI, synergism
中文翻译：
蟛蜞菊内酯和顺铂组合对 HeLa 细胞系的协同细胞毒性作用：一项新发现
背景和目的：顺铂是目前临床上用于治疗宫颈癌的铂类药物。然而，药物毒性和耐药性是其两大局限性。本研究的目的是测试潜在植物化学物质单独以及与顺铂联合使用对宫颈癌细胞的细胞毒活性。
方法：在本研究中，通过 3-(4, 5-二甲基-2-噻唑基)- 研究了植物化学物质包括蟛蜞菊内酯 (WDL)、桦木酸 (BA) 和表没食子儿茶素没食子酸酯 (EGCG) 在人宫颈癌细胞系 HeLa 中的细胞毒性。 2、5-二苯基-2H-溴化四唑（MTT）还原测定。通过中值效应原理在同一细胞系中研究了顺铂与 WDL 和 BA 组合产生的联合药物作用。联合指数（CI）作为联合药物作用的量度。
结果： BA与顺铂在0/0时联合给药时产生协同作用；（推注给药），而其中一种药物（顺铂或 BA）比另一种药物（0/4 或 4/0）早 4 小时给药，导致拮抗作用。另一方面，发现 WDL 在任何给药顺序（0/0、0/4 或 4/0）下都具有协同作用。
讨论和结论：这是第一项报告 WDL 作为单一药物或与顺铂联合使用对 HeLa 细胞的细胞毒活性的研究。这些结果支持顺铂与 WDL 和 BA 序贯组合可能在宫颈癌细胞中有效发挥作用的观点。
关键词： HeLa，蟛蜞菊内酯；WDL，桦木酸；BA、MTT还原试验、组合指数；CI，协同作用
更新日期：2020-09-22
Methods: In this study, cytotoxicity of phytochemicals including wedelolactone (WDL), betulinic acid (BA) and epigallocatechin gallate (EGCG) was investigated in human cervical cancer cell line HeLa through 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay. Combined drug action resulting from the combination of cisplatin with WDL and BA was investigated in the same cell line through median effect principle. The combination index (CI) was taken as a measure of combined drug action.
Results: BA resulted in synergistic outcome when co-administered with cisplatin at 0/0 time; (bolus administration) while administration of either drug (cisplatin or BA) four hours before the other (0/4 or 4/0) resulted in antagonistic action. WDL, on the other hand, was found out to be synergistic at any of the applied sequence of drug administration (0/0, 0/4 or 4/0).
Discussion and Conclusion: This is the first study reporting cytotoxic activity of WDL in HeLa cells either as single agent or in combination with cisplatin. These results support the idea that sequential combination of cisplatin with WDL and BA may work effectively in cervical cancer cells.
Keywords: HeLa, wedelolactone; WDL, betulinic acid; BA, MTT reduction assay, combination index; CI, synergism
中文翻译：
蟛蜞菊内酯和顺铂组合对 HeLa 细胞系的协同细胞毒性作用：一项新发现
背景和目的：顺铂是目前临床上用于治疗宫颈癌的铂类药物。然而，药物毒性和耐药性是其两大局限性。本研究的目的是测试潜在植物化学物质单独以及与顺铂联合使用对宫颈癌细胞的细胞毒活性。
方法：在本研究中，通过 3-(4, 5-二甲基-2-噻唑基)- 研究了植物化学物质包括蟛蜞菊内酯 (WDL)、桦木酸 (BA) 和表没食子儿茶素没食子酸酯 (EGCG) 在人宫颈癌细胞系 HeLa 中的细胞毒性。 2、5-二苯基-2H-溴化四唑（MTT）还原测定。通过中值效应原理在同一细胞系中研究了顺铂与 WDL 和 BA 组合产生的联合药物作用。联合指数（CI）作为联合药物作用的量度。
结果： BA与顺铂在0/0时联合给药时产生协同作用；（推注给药），而其中一种药物（顺铂或 BA）比另一种药物（0/4 或 4/0）早 4 小时给药，导致拮抗作用。另一方面，发现 WDL 在任何给药顺序（0/0、0/4 或 4/0）下都具有协同作用。
讨论和结论：这是第一项报告 WDL 作为单一药物或与顺铂联合使用对 HeLa 细胞的细胞毒活性的研究。这些结果支持顺铂与 WDL 和 BA 序贯组合可能在宫颈癌细胞中有效发挥作用的观点。
关键词： HeLa，蟛蜞菊内酯；WDL，桦木酸；BA、MTT还原试验、组合指数；CI，协同作用
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